Emerging infectious disease (EID) events have the potential to cause devastating impacts on human, animal and environmental health. A range of tools exist which can be applied to address EID event detection, preparedness and response. Here we use a case study of rabies in Southeast Asia and Oceania to illustrate, via nearly a decade of research activities, how such tools can be systematically integrated into a framework for EID preparedness. During the past three decades, canine rabies has spread to previously free areas of Southeast Asia, threatening the rabies-free status of countries such as Timor Leste, Papua New Guinea and Australia. The program of research to address rabies preparedness in the Oceanic region has included scanning and surveillance to define the emerging nature of canine rabies within the Southeast Asia region; field studies to collect information on potential reservoir species, their distribution and behaviour; participatory and sociological studies to identify priorities for disease response; and targeted risk assessment and disease modelling studies. Lessons learnt include the need to develop methods to collect data in remote regions, and the need to continuously evaluate and update requirements for preparedness in response to evolving drivers of emerging infectious disease. Staphylococcus aureus (MRSA) in the 1980s and 1990s [Priorities for epidemiologic investigation of disease are dynamic: they change continuously on global and local scales, as well as over the short and long term. In the 1960s, following the advent of antimicrobials and vaccination, epidemiologic focus shifted towards chronic, non-infectious disease; further advancement of the control of infectious disease was considered more likely to be delivered through laboratory-based research rather than epidemiology [nd 1990s ,3,4,5. BAs expected, the impacts of EIDs continue in the 21st century. Diseases newly emerge , re-emeA systematic approach that integrates epidemiologic methods has previously been described . The appIn this review, we evaluate a program of research conducted between 2012 and 2019 in response to changes in the distribution of rabies in Southeast Asia, in the context of this systematic, integrated approach to disease preparedness. Although rabies is endemic in many parts of the world, it has recently re-emerged in historically or previously free regions of Indonesia and Malaysia. The program aimed to develop strategies for rabies preparedness and response in Australia given the perceived increase in risk of a rabies incursion in the Oceanic region. Lyssavirus; it causes an acute, progressive neurological disease in susceptible species. The genus Lyssavirus contains more than 16 species, generally maintained in wildlife (and often bats). RABV is the most widespread Lyssavirus and although RABV can infect all mammals, the most common maintenance hosts are canids.Rabies is one of humanity’s oldest neglected infectious diseases . Rabies It is likely that Eurasia was the historical source for the spread of canine rabies to other regions, centuries ago, via trade and colonization . Rabies The most common source of human RABV infection are domestic dogs, responsible for >95% of human cases . Rabies Clinical signs of rabies in animals can only be used for presumptive diagnosis because the different forms of clinical rabies  have signs that are similar to other diseases, and vary between individuals. Definitive rabies diagnosis is via laboratory tests to identify rabies viral particles in tissue samples from suspect animals. The gold standard test recommended by the WHO and the OIE is the direct fluorescent antibody (DFA) test ,21, in wInterventions focused on rabies elimination in dogs are the key to reducing human rabies incidence and recurrent costs ,23,24. AThe rabies situation in Asia is characterised by high human mortality: it is estimated that more than 35,000 people in Asia die each year from rabies, which represents 60% of the global burden . Only a Currently, rabies is endemic in all Southeast Asian countries, except Singapore, Timor-Leste and Brunei Darussalam . All of Historically, Australia has remained canine rabies free. RABV infection has never been documented in the native fauna of Australia. An incursion of RABV was suspected around Hobart (in the island state of Tasmania) in the period 1866–1867 ,36,37. UDasyurus spp.) is unknown, but due to presumed low abundance and limited distributions, native carnivorous mammals have not been considered a high risk for RABV transmission in Australia [Consequently, due to strong quarantine regulations on the importation of susceptible species, the risk of RABV to Australia was largely discounted. However, in the 1980s there was increasing recognition of disease threats to northern Australia . Dingoesustralia . Rabies ustralia , the firustralia .The recognition that northern Australia faced disease threats from both regulated and unregulated  pathways—which were expected to increase in activity as this region was developed in response to economic drivers—and that a large, susceptible and potential reservoir species existed in this region, thus increasing the risk of RABV to Australia is an example of using information from environmental and horizon scanning . These aad hoc basis to meet current and anticipated needs [Environmental scanning to enhance EID preparedness is usually developed on an ed needs . It colled needs . InformaInformation collected from scanning can be used in foresight activities such as scenario planning, causal layered analysis, and backcasting ,49,50. PIn 1997, canine rabies spread to Flores Island, Indonesia , then AmThus, a link between the movement of dogs via inter-island fishing and rabies spread in eastern Indonesia was known. Within an environmental scanning framework, changes in fishing patterns—for example, in response to changing markets and economic drivers—would be expected to have an impact on the risk of rabies incursions. It is of note that traditional fishing by the Buginese and Makasarese people of southern Sulawesi has occurred in this region for centuries; prior to the British colonization of northern Australia in the late 19th century, fishing on the Arnhem Land coast of northern Australia occurred, as well as trade with the local Aboriginal people. Although formal foresighting activities were not conducted, this emergence of rabies in previously free regions in eastern Indonesia prompted a re-evaluation of the risk to the Oceanic region . The risThe rabies research program described below was then instigated to investigate the risk of an incursion to Australia and neighbouring PNG, and the response and control strategies that would be required given the potential impact of rabies in Australia. The program integrated a variety of methods from the field of prioritisation, risk assessment and disease modelling .In the first stage of the program, prioritisation of routes of incursion and detailed risk analysis of these routes were undertaken. Given the high-risk areas for a rabies incursion along the northern Australian coastline and the possibility of an incursion to PNG , these areas were prioritised.Prioritisation uses methods borrowed from the field of decision analysis, that range from qualitative ranking systems  to quantRisk analysis also comprises qualitative and quantitative methods. It is used in contexts such as import risk analysis to support trade of animals and their products, and food safety. In contrast to prioritisation, the scope is usually narrower and more specific, i.e., a single risk pathway is considered for a defined disease risk. Whilst entry and exposure pathways are included, evaluation of the ongoing impact to a population is addressed by other methods such as scenario or disease modelling. For example, in a study of the impact of West Nile virus in Australia, risk analysis was used to investigate the probability of entry and exposure, and scenario modelling based on the expected spatiotemporal spread was used to investigate equine and human population impact . TherefoIn the rabies program we present here, Cape York Peninsula, Queensland was already identified as high priority for a rabies incursion , and to In contrast to northern Australia, prioritisation of regions, modes or routes of entry for rabies into PNG had not been conducted. Initially, modes of entry were prioritised in a qualitative exercise in which the likely number of dogs (not necessarily rabies infected) were estimated given the volume of types of traffic, number of people and purpose or reason for travel . LoggingAccurate data are important for accurate model predictions. Most rabies risk assessments investigate illegal pathways which makes accurate data inherently difficult to obtain. However, sensitivity analyses highlighted that knowledge of prevalence of rabies at origin is needed to accurately determine the risk of an incursion. In the context of rabies, this is a persistent knowledge gap worldwide, which not only influences the accuracy of risk assessments, but also rabies surveillance and control. Rabies is not detectable prior to development of clinical signs in animals and therefore, the prevalence of rabies in dog populations cannot be accurately determined. Given the potentially long latent period, it is possible for rabies to remain endemic at low prevalence in dog populations.The results of risk analyses are specific to one pathway, and therefore, do not represent the total risk of incursion in Australia. The total risk of an incursion of rabies is additive across many pathways, for each mode of transport and each location. Additionally, risk distribution changes with a range of factors that have political, social and economic drivers. This is particularly important in the context of PNG where the volume of traffic on a pathway most influenced risk, and where ongoing land-use changes associated with logging and the palm oil industry influence human migration across the border from Papua Province, Indonesia. Although Western Province in PNG was identified as the highest-risk region (mainly hunters and logging), this might change in the near future.Overall, unless prioritisation and risk assessments are conducted regularly—either routinely or in response to information from horizon or environmental scanning—investigation of a single pathway or even a group of pathways only gives a snapshot of risk at the time. Therefore, their main benefit lies in sensitivity analyses, which are more likely to be generalisable across pathways. To prevent an incursion in Australia, the most influential strategy would be to reduce prevalence, or eliminate canine rabies at origin—highlighting both the importance of pre-border biosecurity, and global strategies such as ZeroBy30.The objectives of disease modelling are to understand disease spread mechanisms and to make predictions about disease impacts. The latter can be done by simulating spread in a specific population under various circumstances, and in the context of this review we focus on disease spread modelling as a component of disease preparedness. Impacts can be described in terms of disease incidence and distribution , duration of outbreaks, and the economics of control strategies. Such information can be useful for surveillance or response purposes; for example, identifying the highest risk groups in a population for targeted surveillance, and identifying optimal control strategies. Disease modelling is, therefore, a natural progression in a program for disease preparedness following investigation of incursion risks using risk assessment. It is also similar to risk assessment: although sensitivity analysis provides insights about influential parameters, valid predictions (and thus the greatest benefit) depend on accurate data to parameterise the model. In the case of disease modelling, transmission parameters are critical. Therefore, accurate data about the population of interest—such as their demographics, dynamics, movement and contacts—are needed. Following prioritisation and risk assessment of potential routes of incursion, the regions of interest for RABV spread modelling in the program presented here were Western Province, PNG, and the Torres Strait and the NPA, Australia . ConsequIn Australia, dog populations of interest are free-roaming, owned, domestic dogs in remote communities in the Torres Strait and the NPA, and the free-living dingo population in the NPA. Methods to investigate their demographics, patterns of movement and contacts included systematic review of the literature , surveysAgent-based, stochastic, rabies spread simulation models were subsequently developed for domestic dogs in Torres Strait island communities , NPA comIn the context of outbreak response, the NPA model predicted that pre-emptive vaccination strategies that had covered 10–50% of the population and targeted far-roaming dogs rather than dogs that stayed at home reduced outbreak duration and size, especially if the response following outbreak detection aimed to then vaccinate 70% of all dogs. The network-based model of the smaller populations of dogs in the Torres Strait further accounted for heterogeneity of contacts by incorporating rabies-induced behavioural changes. In the context of prevention of disease emergence, it was predicted that maintenance of vaccination of >80% of the population (rather than 70%) was required to prevent emergence of rabies in such populations. These results highlight a feature of models in that outcomes are influenced by the structure of the model even when the same disease is modelled. As was illustrated in this program, the structure of a model is driven by the model’s purpose, and consequently, interpretation of findings should be made only in the context of this purpose. Implementation of model findings in policy is then further determined by social, economic, political and logistical factors that act both locally and more globally. Given the geographic interface that the Torres Strait islands naturally create between PNG and the Australian mainland, and the low likelihood of timely detection of rabies in PNG, we focused on prevention of emergence when modelling rabies in the small populations of dogs in this region and recommend that all domestic dogs in the Torres Strait should be pre-emptively vaccinated. In the case of the NPA, the dog population is larger, but less stable . This makes vaccination logistically more difficult; however, compared to PNG, detection of an outbreak is likely to be more timely given the greater surveillance resources . RecommeRabies spread modelling in the dingo population of the NPA region predicted that a median of 14% of the population  would be infected, with a median rate of spread of 0.52 km/week for 191 days. Predicted outbreaks were larger in scenarios in which an incursion was introduced during the dry season or close to communities. This suggests that although model outputs indicated that the dingo population would not support sustained propagation of rabies, the risk to domestic dogs and people in local Indigenous communities needs to be considered, for example in further investigation of potential control strategies such as ring vaccination around communities. It also highlights that more needs to be known about the nature of the interface between domestic roaming dogs and dingoes . SensitiData on dog populations in Western Province, PNG were more difficult to collect due to the logistic constraints of travel in this region. In 2018, GPS telemetry data were collected from 60 domestic dogs in treaty villages Kadawa, Buzi and Berr, in Western Province, PNG , to estiThe research program presented here has produced many outcomes. In terms of the emergence of canine rabies in the region, it has contributed to policy, response planning and public awareness. For example, the response policy for an incursion of rabies in Australia (AUSVETPLAN) is updated regularly, and the forthcoming update (version 4) will incorporate some findings from the research program such as risk pathways and options for control. In addition, gaps have been identified. These include the need for methods development in remote regions such as PNG, and characterisation of the wild dog–domestic dog interface. These gaps are a challenge particularly for disease spread modelling. Likewise, the use of participatory methods to source information to parameterise risk analysis models within this research program offers an approach to overcoming this data input gap. Some of these methods have been applied successfully in both the Torres Strait and Papua New Guinea ,88,89,90The framework in which this program was conducted only considers rabies in the context of epidemiologic risk (including impact) and the requirements of preparedness. It can be extended by using methods from fields such as anthropology and social science; for example, to determine feasibility and acceptability of strategies. This is particularly important during the translation of recommendations based on epidemiologic outputs into effective policy. Some research was conducted in the area of social norms and behaviours, and how these might influence the recognition of an incursion, and the response that is mounted. For example, in studies conducted in areas identified as high risk of a rabies incursion via risk assessment, dogs and dingoes were found to have great cultural importance, but this varies within and between the communities and has implications for rabies response. Dogs are not equals or deities; nor is harm to them inconsequential. There are also different concepts of ‘ownership’ and dog care practice. During the first phase of a rabies response, seizure and destruction of infected and exposed dogs would be tolerated if prior permission is sought and received, and all animals are treated with respect based on their role as a family member and part of the wider community. A vaccination program would be welcomed, but movement restrictions would be burdensome if not impossible due to poor quality fencing and food security concerns. The culling of healthy dingo populations would be problematic in all settings due to their high cultural importance. The capacity of communities to contribute or adapt to the rabies response policy is variable and limited by the lack of infrastructure and services, lack of appropriate information, dominant cultural norms (among people and dogs) and food security concerns. This research found that communities need to be aware of risks and consequences prior to an outbreak . Social The value of continued environmental and horizon scanning to develop an understanding of drivers of EIDs such as rabies in the Southeast Asian region cannot be underestimated. Despite numerous regional initiatives—including harmonisation of regulatory, strategy and standard guidelines; vaccination and PEP; dog population management; capacity building; and stakeholder engagement—the rabies situation in Southeast Asia has deteriorated over the past three decades, as rabies has spread to areas that were previously free. There has been a resurgence of rabies in Thailand, northern Vietnam and West Kalimantan. The northern part of West Malaysia reported a rabies incursion in 2015, and Sarawak in East Malaysia in 2017. In January 2019, an outbreak in Sumbawa, Nusa Tenggara Barat, Indonesia was reported. Within the context of ongoing rabies spread within the Southeast Asian region, the goal of regional rabies control is challenging. Key technical challenges include inaccurate estimates of the size of dog populations, inconsistent dog population management and low vaccination coverage. Understanding the drivers of rabies spread for strategic prevention of incursions would be beneficial.Surveillance to detect rabies in dogs before humans are affected also remains a challenge. In July 2017, three children in Serian District in the east Malaysia state of Sarawak were admitted to hospital with clinical rabies. East Malaysia (the states of Sarawak and Sabah) was historically free of rabies. In the adjacent Indonesian provinces of Kalimantan, canine rabies had progressively spread since an incursion in East Kalimantan province, reported in 1974. The first reports of rabies from West Kalimantan province, which shares a border with Sarawak, were in 2005 from Ketapang District, in the south of the province. This outbreak was short lived. Rabies then re-emerged in 2014 in Ketapang and Melawi Districts, which both share a border with Central Kalimantan province, the assumed source of the incursion. Between 2014 and 2017, rabies apparently spread throughout West Kalimantan province. By 2018, all districts except the provincial capital had been affected, with increasing reports of dog bites and human rabies cases. During 2018, rabies spread throughout many districts of Sarawak.Apparently, the incursion of rabies into Sarawak was not anticipated. In this situation, environmental and horizon scanning might have identified such a future scenario. However, in 2019 an investigation of drivers of rabies spread and maintenance was undertaken ,92. InfoThe border between West Kalimantan and Sarawak is 857 km in length. There are three official border posts , but there are many unofficial crossing points. For example, in one district with an official border post, there are at least 54 other unofficial crossing points. People generally cross the border at unofficial points to visit family, and for trade and work. Crossing for medical treatment usually occurs at the official border points. Dayak people  regularly cross the border in both directions for trade. Most border crossing is on foot and occasionally motorbike. The border is indistinct  and some households even straddle the border.There are estimated to be 200,000 dogs in West Kalimantan, probably much higher than in adjoining Sarawak. This can be partly explained by the use of dogs (interchangeably) for hunting, protecting homes and crops, as ‘special’ dogs (pets and dog guardians) and for consumption. Many villages in West Kalimantan are predominantly Christian, so dogs are more valued in these villages. Other notable features of West Kalimantan society are harvest festivals (Gawai) and a substantial indigenous population (the Dayak).demand for hunting dogs. In this area, dogs are used to hunt pigs, and it appears that most of the meat is consumed within villages. However, demographic changes in the region  in which there is an increased demand for pig meat and therefore an increased price paid, could be a driver of a larger hunting dog population and therefore increased rabies spread.An increase in demand for dogs to guard crops. Dogs are used within the region to guard crops from wildlife, such as wild pigs and monkeys. As above, an increase in demand for crops due to immigration or socioeconomic changes could drive an increase demand for guard dogs. In 2019, a rabies incursion in Sumbawa, Indonesia was reported. Initial investigations suggested that this incursion in the previously rabies-free island was due to the movement of dogs from either Bali or Sulawesi, Indonesia, for the purposes of guarding corn crops from wild monkeys.An increase in Ethnic, cultural and religious trends. In the district studied, it appeared that in rural areas rabies is more likely in villages that are predominantly Christian, versus those that are predominantly Muslim. It is also likely associated with indigenous Dayak populations. The association between ethnic, cultural and religious affiliations and dog ownership and movement have been previously described [escribed .Gifting of puppies has been linked to the spread of rabies to previously free areas, such as Tanibar, Maluku Province, Indonesia. It appears that gifting puppies is a traditional practice in the region. However, increased disposable income and an increase in pet shops or other pet traders might increase the risk of rabies spread.Dog meat consumption. Most dogs appear to eventually be consumed when their other uses are exhausted. This is a local activity and likely not a potential driver of regional rabies spread. However, the most likely reason for long-distance movement is supply of dogs for consumption  if dogs for consumption are scarce in the local area. Gawai  are held in every village between January and July. The time varies between villages due to the harvest time. There is also a district Gawai. Dogs are consumed during these festivals. This system of festivals appears to be relatively constant (and perhaps even decreasing in popularity). Changes that promote traditional festivals—such as an increase in tourism—could create a scenario of rabies spread via dog movements for consumption.Regional road improvements. Major roads throughout the region have been sealed within the past 5 years. Better roads enable increased trade and travel. If dogs are taken on such trips, then the risk of rabies spread can be expected to increase in a future scenario.Oil palm plantations. The increasing number of oil palm plantations in the region has provided opportunities for work and trade. The oil palm plantations are numerous on the Malaysian side of the border and have increased unofficial, local border travel. Indonesians work on Malaysian owned plantations  and also trade . Dogs are used on oil palm plantations for protection, although details on the roles played by dogs on oil palm plantations are not readily available.The scanning of several information streams might have led to scenarios in which an incursion of rabies from West Kalimantan to Sarawak were a feature. These include:Information on some of the above are likely available; for others, sourcing information might be challenging. For example, information on roads tends to be readily available in most countries and regions via satellite imagery and GIS. Data include the total length of roads, the number and length of major and sealed roads, and the connectivity of the road network. In some cases, traffic volumes (including at the number of passengers and amount of freight) are available. Therefore, changes in the road infrastructure and network can be scanned to determine if risk of spread of a contagious disease is increasing or decreasing. In contrast, in the border area of West Kalimantan and Sarawak, information on oil plantations is less readily available—although crude measures of the changes in area under management is possible via satellite imagery. Changes in economic activity and disposable income are often available. However, more proximal changes in drivers of the spread of a disease such as rabies—the number and cost of dogs—often are not. Here, an alternative might be to scan the prices of dogs for sale at markets or in pet shops. The initial incursion of rabies in West Kalimantan was in the southern district of Ketapang. This district is known for its restaurants which serve dog meat. Scanning the prices paid in these restaurants would provide a data source to inform disease incursion scenarios. An issue when considering information sources and their ease of access is whether the activity is legal or not.Overall, a systematic, integrated research program for rabies preparedness in the Oceanic region was feasible using our previously described framework. In circumstances in which data were limited, some outputs were limited . Whilst this is a barrier to any research, using the framework clearly identified the gaps and the ongoing requirements for preparedness. The framework is iterative at all stages, which serves as a reminder that outputs need to be updated as inputs evolve. The situation in West Kalimantan, Sarawak and Sumbawa illustrate not only the need for continuous assessment of data streams, but also continuous updating of research outputs to re-evaluate priorities, risks and potential impacts of rabies spread.Surveillance for a disease such as rabies in a resource-limited setting is challenging to maintain over time , and rouMost programs in human and animal health tend to be disease specific and consequently, a systematic framework such as that described in this paper only vertically integrates investigations to develop prevention, detection and response strategies. Focusing on response to one disease can be detrimental to the control of others, and the COVID-19 pandemic has highlighted that horizontal integration across diseases and human and animal health sectors is important and should not be overlooked. For example, a recent modelling study suggests that reduced dog vaccination and rabies surveillance due to COVID-19 control measures in Arequipa, Peru will result in increased human risk due to rabies . In a brFinally, given the goal of ending human deaths from dog-mediated rabies by 2030 (“ZeroBy30”), the need to prevent the spread of rabies to areas historically free of disease—and also the spread to areas where dog-mediated rabies has been eliminated—will become increasingly important in the latter phases of the campaign to achieve this goal. ZeroBy30 will also require further development of appropriate surveillance methods to demonstrate freedom from rabies and timely detection of incursions.Although a range of tools have been developed which can be applied to address EID event detection, preparedness and response, a systematic approach that integrates these tools has rarely been applied. Considering the number and characteristics of these tools, it can be daunting to begin such a process: threats are dynamic and evolving, and data needs can be overwhelming. However, the application of foresighting techniques can begin simply by monitoring those factors known to promote EID events, such as changes in trade, animal management and transportation; such information is collected through environmental and horizon scanning. This can be integrated with passive surveillance data to provide intelligence on threats. Simple, qualitative risk assessments can also add value. As these activities mature and outputs are integrated, gaps become apparent and additional data collection can be planned to parameterise more complex risk assessment and disease spread models, as required. As part of a dynamic system, outputs from such models likely will direct further research to fill data gaps.The information generated needs to be evaluated regularly in terms of the goal of such a framework, i.e., reduce the probability of an EID event and, should an EID event occur, detect it early and mitigate its impact. In addition, the scale at which activities need to take place , and how policies generated are implemented , need careful consideration for effective outcomes.


Clinical assessments often use complex picture description tasks to elicit natural speech patterns and magnify changes occurring in brain regions implicated in Alzheimer's disease and dementia. As The Cookie Theft picture description task is used in the largest Alzheimer's disease and dementia cohort studies available, we aimed to create algorithms that could characterize the visual narrative path a participant takes in describing what is happening in this image. We proposed spatio-semantic graphs, models based on graph theory that transform the participants' narratives into graphs that retain semantic order and encode the visuospatial information between content units in the image. The resulting graphs differ between Cognitively Impaired and Unimpaired participants in several important ways. Cognitively Impaired participants consistently scored higher on features that are heavily associated with symptoms of cognitive decline, including repetition, evidence of short-term memory lapses, and generally disorganized narrative descriptions, while Cognitively Unimpaired participants produced more efficient narrative paths. These results provide evidence that spatio-semantic graph analysis of these tasks can generate important insights into a participant's cognitive performance that cannot be generated from semantic analysis alone. Asking patients to describe a complex picture is a mainstay of clinical assessment tasks in aphasia, and increasingly so in the context of cognitive decline and dementia . This taThe Cookie Theft picture description task from the Boston Diagnostic Aphasia Examination  is the mWhile there is nothing particularly special about The Cookie Theft picture itself—and indeed it has been criticized and even revised for being outdated and culturally non-inclusive , 12—the While the promise of cognitive-linguistic and acoustic metrics in the analysis of picture descriptions is high, these approaches leave important information on the table. In particular, they underspecify the ways in which the patient navigates the visual scene to “describe everything that is happening in the picture,” per the task instructions. Describing a picture has been shown to invoke the expected cortical pathways underlying semantic retrieval and production for the objects in the picture , but also to pathways linking aspects of the parietal lobe with posterior cortical circuits activated for visual processing of a picture . There ispatio-semantic graphs—mathematical models that encode the sequential listing of content units in a transcript and their relative spatial position in The Cookie Theft image. Previous studies have shown the value of analyzing the lexical sequence via visual analyses and automatic speech recognition on recorded Cookie Theft descriptions to classify participants as AD or as healthy  + DementiaBank databases. We conjectured that by tracking the spatial movement paths from semantic object to semantic object, the results would reflect a culmination of visuospatial, attentional, and organizational capabilities. To that end, we apply graph theory and introduce the concept of  healthy , and via thought . Along thttps://dementia.talkbank.org) consists of audio-recorded data collected as part of a larger protocol administered by the Alzheimer and Related Dementias Study at the University of Pittsburgh School of Medicine (n = 99 participants) were combined with Cognitively Unimpaired-Stable participant data from WRAP ; particContent-information-units (CIUs) used in this study were adapted from Croisile et al. , further coordinate pairs on a pixel scale on a picture of The Cookie Theft (the copy used was 546 × 290 pixels). All participant transcripts were processed in Python. The 23 CIUs were manually assigned via a Euclidean distance between two nodes connected by an edge). Additionally, each CIU was attributed a quadrant of the picture. Quadrant information was also processed in NetworkX to analyze and visualize participants' transitions between and within quadrants of the picture. In this representation, the nodes in the graph represent the quadrants of the image and the edges represent how the participant is moving across different quadrants as they describe the picture. Examples of transformed participant transcripts as graphs are also shown in Transcripts from the WRAP and DB databases already have CIUs manually labeled, and these labels and their order of occurrence in the transcript were extracted and automatically encoded with the corresponding coordinate pairs. Next, the NetworkX package was used to transform the CIUs with their corresponding features, including coordinate pairs, and orderings into a set of nodes and edges that can be analyzed and visualized as a graph . The graAfter transforming the participant transcripts into nodes and edges, several features from the graph were calculated. These features were extracted from the graph representation and the relative spatial position of the CIUs in the image. Additionally, metrics based on quadrant transitions were calculated from participants' transitions within and between these collective nodes. The features, their calculation, and their interpretation are described in For the statistical analysis, two sets of ANCOVA models were used to determine whether there exist group-level differences in the features in n = 1,116) of the diagnosis independent variable, and the Impaired but not MCI and MCI/Dementia diagnosis groups were combined into the Cognitively Impaired level (n = 233). For the second set, CUS and CUD were used as the two levels of the diagnosis independent variable while Impaired but not MCI and MCI/Dementia groups were omitted. The purpose of the second analysis was to determine whether the spatio-semantic graph features capture pre-clinical changes. Each individual feature was used in its own ANCOVA model as the dependent variable, with demographic data  as well as the Unique Nodes variable as covariates. We adjust for Unique Nodes, which is a proxy for the number of content units in the transcript, as it was expected to vary between the Cognitively Unimpaired and Cognitively Impaired groups. To verify this, an initial one-way ANCOVA was performed comparing how these two participant groups differed in the number of Unique Nodes mentioned, while controlling for age, education, and gender. The data for all ANCOVA models were checked for homogeneity of variance (or homoscedasticity) using Levene's test. A significant result indicates that the null hypothesis that the diagnosis groups have equal population variances should be rejected. This violation of one of the assumptions to run an ANCOVA can lead to a decrease in the power of the test , Cycles, Total Path Distance. Levene's test revealed unequal variances for all but the Average x feature.Six dependent variables achieved significance at x position of mentioned nodes  and higher Standard Deviation of x compared to the Cognitively Unimpaired group, as well as a higher Total Path Distance/Unique Nodes, Total Path Distance, Cross Ratio (quadrants), Number of Cycles, and Number of nodes mentioned.Comparing the marginal means for these features showed that the Cognitively Impaired group had a lower Average p-values less than the threshold value of 0.05, the Total Path Distance/Unique Nodes feature had a p-value close to this threshold value. The marginal means show that the Cognitively Unimpaired-Declining group had a higher Total Path Distance/Unique Nodes. Additionally, Levene's test failed to reject the null hypothesis that the variances are equal for this feature.The bottom section of via the graph nodes) and their co-occurrence (via the graph edges), we additionally visualize the transcripts and CIUs in the two-dimensional space relative to the Cookie Theft picture itself.The ability to identify pre-clinical cognitive changes is essential to the development of interventions that halt or slow irreversible neurodegeneration. The Cookie Theft picture description task has been widely studied for its ability to elicit symptoms associated with early dementia and Alzheimer's disease , 25. In x). This is notable because the right side actually contains more target CIUs than the left, but its full description requires more abstract inferences  than does the left side. This finding is corroborated by a study also using data from the DementiaBank database, in which many of the spatial neglect features indicated that the participants with dementia were less perceptive on the right side of the image (x). This attention shifting by the Cognitively Impaired group was also evidenced by the Cross Ratio feature, with a higher number of crossings between quadrants than staying within a quadrant during their description, and more sporadic internode transitions and node repeats than the Cognitively Unimpaired group.The first analysis revealed differences between the cognitively impaired and cognitively unimpaired groups that may reflect a combination of deficits in visuospatial, attentional, and organizational abilities. With regard to spatial orientation, the Cognitively Impaired group described more of the left side of the picture than the right, in contrast to the Cognitively Unimpaired group , and longer descriptions to reach a similar number of CIUs as the Cognitively Unimpaired group . This finding aligns with prior work showing reduced density of information and increased use of non-specific words in cognitive decline , 29, 30.p = 0.0503), with marginal means of 136 for CUS and 142 for CUD. It is of note that this trend is similar to that observed in the comparison between the Cognitively Unimpaired and Cognitively Impaired groups. This overall pattern suggests that spatio-semantic graphs be further explored in preclinical and mild populations for evidence of early cognitive changes. It is likely that larger sample sizes are required to adequately assess the value of these features in these early clinical populations.The second analysis attempted to find features that distinguished performance between the two Cognitively Unimpaired groups, CUS and CUD. As both groups are characterized by normal cognition, any differences that may implicate cognitive decline would be expected to be subtle and difficult to detect. We found that one feature, Total Path Distance/Unique Nodes, approached statistical significance  that reached significance, Average stimated . The larstimated . Such anThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Health Sciences Institutional Review Board of the University of Wisconsin and the other medical centers involved in data collection. The patients/participants provided their written informed consent to participate in this study.PA, RK, VB, JL, and KM contributed to the writing and editing of the manuscript. PA and KB performed statistical analyses. All authors contributed to manuscript revision, read, and approved the submitted version.This research was supported by the National Institute on Deafness and Other Communication Disorders, National Institutes of Health Grant R01DC006859; National Institute on Aging (NIA), NIH Grant R01AG027161; NIA R01AG070940; NIA R01AG054059; NIA AG03705; and NIA AG05133.VB and JL are cofounders and have equity in Aural Analytics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential of conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


I argue that the inclusion of temporal and social information is of particular importance for the study of lexical innovation since neologisms exhibit high degrees of temporal volatility and social indexicality. More generally, the present approach demonstrates the potential of social network analysis for sociolinguistic research on linguistic innovation, variation, and change.Societies continually evolve and speakers use new words to talk about innovative products and practices. While most lexical innovations soon fall into disuse, others spread successfully and become part of the lexicon. In this paper, I conduct a longitudinal study of the spread of 99 English neologisms on Twitter to study their degrees and pathways of diffusion. Previous work on lexical innovation has almost exclusively relied on usage frequency for investigating the spread of new words. To get a more differentiated picture of diffusion, I use frequency-based measures to study temporal aspects of diffusion and I use network analyses for a more detailed and accurate investigation of the sociolinguistic dynamics of diffusion. The results show that frequency measures manage to capture diffusion with varying success. Frequency counts can serve as an approximate indicator for overall degrees of diffusion, yet they miss important information about the temporal usage profiles of lexical innovations. The results indicate that neologisms with similar total frequency can exhibit significantly different degrees of diffusion. Analysing differences in their temporal dynamics of use with regard to their age, trends in usage intensity, and volatility contributes to a more accurate account of their diffusion. The results obtained from the social network analysis reveal substantial differences in the social pathways of diffusion. Social diffusion significantly correlates with the frequency and temporal usage profiles of neologisms. However, the network visualisations and metrics identify neologisms whose degrees of social diffusion are more limited than suggested by their overall frequency of use. These include, among others, highly volatile neologisms (e.g.,  Societies continually evolve, new products and practices emerge, and speakers coin and adopt new words when they interact and share information. How do these new words spread in social networks of communicative interaction?Nature Physics, In a recent paper analysing contagion patterns of diseases in Social media platforms like Twitter have changed the way we communicate and how information spreads, and they offer valuable data for empirical research. For linguists, social media provides large amounts of data of authentic language use which opens up new opportunities for the empirical study of language variation and change. The size of these datasets as well as their informal nature allow for large-scale studies on the use and spread of new words, for example, to gain insights about general trajectories of diffusion  or aboutData about the communicative interaction of speakers additionally allows performing network analyses of the social dynamics of diffusion processes. Network science approaches to social media data have been successfully employed in diverse fields, for example, to study the spread of diseases , opinionIn the area of lexical innovation, this can serve to evaluate important theoretical concepts like the role of early adopters, network density and weak ties in the diffusion of new words. For example, previous approaches have used computational modelling to test the validity of the S-curve model , and to This paper aims to explore the role of network information and temporal dynamics in assessing the diffusion of lexical innovations on Twitter. I use several quantitative and qualitative methods to study diffusion. I conduct a longitudinal study monitoring the use of a broad sample of neologisms to analyse their usage frequency and the temporal dynamics underlying their use. Next, I use social network analyses to get a better picture of the sociolinguistic dynamics at play, to assess different pathways and overall degrees of diffusion. Lastly, I combine both approaches to get a more detailed picture of the diffusion of the neologisms in the sample, and to assess the results of both approaches to diffusion.The paper is structured as follows. Neologisms are on a continuum from entirely novel word-formations to fully established lexemes which are familiar to the majority of the speech community. Neologisms have spread to some extent, but are still perceived as new or unknown by many speakers . On one Diffusion can be seen as the process that transports successful neologisms along this continuum while they are becoming increasingly conventional in the speech community. The S-curve model  expects a change in the number of speakers and communities who conform to a regularity of co-semiotic behaviour and a change in the conformity regarding the types of cotexts and contexts in which they use it.’  or begpacker (‘backpackers funding their holidays by begging’).The grouping of neologisms on the basis of their total usage frequency presented in millennium bugcoronavirus, which have already become familiar to the vast majority of speakers, but show comparatively moderate total frequency counts, since they have started to diffuse only fairly recently.However, total frequency counts only provide a limited picture of diffusion since they are insensitive to temporal dynamics of usage. Neglecting temporal information about the lifespan and the period of active use of a new word can distort the quantitative assessment of its degree of conventionality in two directions. Firstly, it carries the danger of overestimating the status of words such as twitterverse and blockchain, for example, have similar total frequency counts, but differ significantly with regard to their temporal usage profiles. The neologism twitterverse has been in use ever since the start of Twitter, while the diffusion of the much younger blockchain only started in 2012. Despite its shorter lifespan, blockchain accumulated roughly the same number of uses, but shows significantly higher usage intensity in the more recent past, and can be assumed to be familiar to bigger parts of the speech community.Among the most frequent neologisms presented in Similar effects are even more pronounced in the remaining groups of neologisms, since words from the lower ranges of the frequency spectrum are typically affected more strongly by temporal variation in their use. In the following sections, I will include temporal information to get a more fine-grained picture of diffusion.Visualising the cumulative increase in usage frequency of new words complements total counts by taking into account the temporal dynamics of their usage intensity over time. hyperlocal, for example, is the oldest new word among the selected neologisms, and it is commonly used to refer to information that has a strong focus on local facts and events. While it was hardly used in the first years of Twitter, it started to increase in its use in 2009 and was added to the OED’s Third Edition in 2015. Around this time, the neologism solopreneur only started to significantly increase in its use. A blend of solo and entrepeneur, it keeps a low, flat trajectory of sporadic use for about 7 years after its first appearance in the corpus. The first two attestations in the corpus indicate the sense of novelty and scepticism towards the term in its early phases:1) I’m trying to figure out if I like the term ‘solopreneur’ I just read .2) hmmmmmmm new word added to my vocab = ‘solopreneur’ !! .While the end points of the trajectories in Free Tools for Writers, Bloggers and Solopreneurs by solopreneur as compared with hyperlocal, even though the use of the latter term shows a longer lifespan of continual useMost speakers increasingly ‘like the term’ and ‘add them to their vocabulary’ only much later, after 2014, when the phenomenon of individual entrepreneurship attracts increasing conceptual salience in the community, which seems to be both reflected and propagated by the publication of several self-help books for entrepreneurs in this year, which all explicitly use this new term in their titles  show a steady, gradual increase in usage frequency over longer periods of time. By contrast, the use of other candidates such as solopreneur and alt-left is much less stable and less evenly distributed over time.Neologisms such as solopreneur, we observe a big spike in frequency following its increased popularity in the entrepreneurial community in 2014. While it shows the highest total frequency count in In the case of alt-left, which is the youngest neologism to enter the scene at the end of 2015. alt-left was coined as a counterpart to the term alt-right. The latter neologism is a shortening of Alternative Right, introduced by the white-supremacist Richard Spencer in 2010 as a new umbrella term for far-right, white nationalist groups in the United States. Facing substantial criticism for racist attitudes and actions, proponents of this far-right political camp coined and attempted to propagate the derogatory term alt-left to disparage political opponents. Despite its late appearance in the corpus, alt-left occurs in a total of 163,809 tweets, which places it in the medium range of the sample in terms of total frequency counts. However, its trajectory in An even shorter and steeper increase can be seen in the use of The cumulative increase in usage intensity of the selected neologisms illustrates that similar total frequency counts of neologisms can be the product of highly different trajectories of diffusion. These data complement total counts in that they show differences in the total lifespan and in the intensity with which a given neologism was used over time – types of information that are highly relevant for assessing the degree to which they have spread in the speech community.Going beyond cumulative counts, absolute usage frequency counts provide a more fine-grained view of the temporal dynamics of diffusion. Most importantly, analysing usage intensity highlights to what degree new words are being used consistently over time. upskill and hyperlocal are much older than alt-right and alt-left. The absolute counts also highlight the fact that while there is a low level of use of solopreneur since 2007, its main period of diffusion starts much later, in 2014, with a subsequent spike in usage intensity.The absolute frequency plots confirm differences regarding the lifespan and dynamics of usage intensity among the neologisms discussed above. In terms of lifespan, Besides, the absolute frequency counts over time provide a more detailed picture of the temporal dynamics of use. While the cumulative counts in upskill shows the smoothest trajectory of diffusion among the candidate neologisms in The neologism hyperlocal also exhibits a marked increase in usage frequency during its earlier stages, its peak in popularity is followed by a decline in use, after which it settles at a relatively stable level of about 1,000 tweets per month. This coincides with the OED’s decision to take up hyperlocal in its 2015 edition. Despite fluctuations, hyperlocal has been used relatively consistently in the recent past.While solopreneur has been in use since 2007 and shows an overall increase in usage frequency, but its use fluctuates more strongly than that of hyperlocal. After its initial peak around 2015, which coincides with the release of several self-help books featuring the term, its frequency plummets, becomes less stable, and shows an overall downward trend.The neologism alt-right and alt-left are closely related. Both terms show high levels of volatility in their usage frequency. The former, older term shows significant diffusion in 2016, particularly in the period leading up to Donald Trump’s election, after which alt-right remains in consistent use to a relatively high degree, at about 25,000 tweets per month. Its counterpart, alt-left, enters the scene much later, during the infamous Charlottesville Rally in 2017, whose topical effect causes a huge spike in the use of both terms. However, unlike alt-right, which reverts to its previous usage intensity, the use of alt-left seems to largely disappear from Twitter in the aftermath of the event.As was mentioned above, poppygate, also exhibits high degrees of volatility, and it features the most distinctive pattern of spikes in its usage intensity. Unlike the single topical spike for alt-right and alt-left, its use follows a recurrent, regular pattern: speakers use it almost exclusively around Remembrance Day, which takes place in November. The term poppygate represents a last category of neologisms in the sample, which show strong fluctuations in usage intensity, but for which these patterns follow a regular temporal pattern.The final example among the selected candidates, To quantify the degree to which neologisms are used with consistent frequency over time, I calculate and compare the coefficients of variation for each neologism in the sample. This metric captures the overall volatility in usage frequency of words over their lifespan relative to their average frequency of occurrence in the corpus. twitterverse is listed among the most frequent neologisms in The results in alt-left and birtherupskirtingyouthquakepoppygate and cherpumpleBy contrast, the group of lexemes that show the highest degree of volatility in usage frequency is comprised of neologisms with lower degrees of conventionality, which are generally less frequent and were coined more recently. Notably, topical spikes play a crucial role in the diffusion processes of all examples in this category: the diffusion of The selected neologisms cover the spectrum of volatility in usage frequency found in the full sample of neologisms, and the coefficients of variation represent quantitative measures which reflect the differences in volatility between the selected neologisms visualised in alt-left, for example. However, its usage history reveals that its use largely goes back to a short period of high usage intensity linked to a specific topical event. The term’s background suggests that it might not have spread far beyond one particular community of speakers. Such potential distortions of frequency-based measures could partly be resolved by in-depth analyses of temporal usage profiles combined with insights from corpus data and extralinguistic events. However, these in-depth analyses of diffusion are not possible through a systematic frequency-based analysis alone, and they cannot be extended to the large-scale study of larger samples of neologisms. Hence it remains unknown to what degree frequency-based metrics adequately capture social pathways of diffusion. In the following section, I will complement the frequency-based approach by social network analyses to get a more differentiated view of the sociolinguistic aspects of diffusion.The present data demonstrate considerable variation in the degrees of diffusion of neologisms with similar frequency of occurrence in the corpus. Total frequency counts alone would predict high degrees of diffusion for neologisms such as As described in As discussed in For example, the social graph users of a new word shows high centralization in early stages when its use is largely confined to one or few centralized clusters of speakers. When increasing diffusion extends the use of the term to new speakers and communities, the distribution of interactions in the speech community shows greater dispersion, which should be reflected by lower centrality scores for the social network of speakers.The neologisms with the lowest scores for degree centrality are also among the most frequent lexemes in the sample. Overall, frequency and centrality generally tend to produce similar results when used to assess degrees of diffusion. This shows usage frequency and social diffusion correlate, as one might expect. Notable deviations exist, however, and will be further discussed in dronographyecocideKushnergaterapugee which are controversially discussed on the left and right ends of the political spectrum. For example, rapugee is a derogatory term which was coined after sexual assaults by refugees during New Year’s Eve 2015/16 in Cologne, Germany. Previous work has shown that this term was consciously coined and propagated by a closely connected community of far-right activists to disparage refugees, and that its use on Twitter and on the Web has remained largely limited to these communities  and to distance themselves from and protest against the political left. Inspection of the network reveals that the most influential node in the network is Donald Trump. His use of the term was followed by a sharp increase in usage intensity in the course of the Charlottesville Rally in August 2017. The high degree of social compartmentalization in the use of alt-left is also reflected in the ratio between the number of nodes and edges in its graph, which confirms that its community of speakers is much more closely connected than that of the remaining neologismsalt-right, which occupies the opposite pole of the political spectrum. The results for these two terms are in line with previous work reporting effects of political polarization in online social networks for these political communities  reveals that hyperlocal is mainly used by a relatively small community of individual journalists in the first subset, who are early adopters in trying to target news to local audiences and use the term very frequently to label this new approach.Both the quantitative measure in The Guardian. Additionally, a new community of practice adopts the term: several marketing agencies start promoting their services using the term hyperlocal. At this point, the usage intensity of the term peaks, as was demonstrated in In Subset 2, the community of journalists grows and starts to include also bigger news outlets such as hyperlocal is only significantly advanced in the last two stages. While we see only few weak ties during the earlier stages of its use, the term now increasingly diffuses beyond its early adopters. Inspecting the network reveals that the use of the term becomes increasingly popular in the world of business and startups as well as the general public on Twitter. The network metrics indicate that individual agents and sub-communities now play a far smaller role in its overall use. While hyperlocal shows less usage intensity during these later stages, the network metrics indicate a high degree of diffusion for the second half of its observed lifespan. The timing of its addition to the OED in 2015 supports these observations. The term hyperlocal has successfully spread beyond its subcommunities of early adopters, and it seems to be used by a diverse community of speakers from different backgrounds, which renders it a case of advanced diffusion. This process of increasing diffusion for hyperlocal is also reflected in its decreasing measures for graph centrality in The network graphs show that the social diffusion of The remaining cases in hyperlocal, the second neologism which exhibits advanced diffusion is upskill. In this case, however, we observe little change over time, its degree centrality has been very low since its early attestations in the corpus. This indicates a gradual spread across speakers which is not significantly affected by a small group of influential speakers. The term upskill has been used by a wide variety of speakers throughout its observed lifespan and shows the highest degree of diffusion among the selected cases.Besides solopreneur and poppygate show a negative trend in terms of diffusion. The term solopreneur features low degrees of diffusion in its earlier stages, but its use becomes more centralized over time. This is in contrast with its usage intensity over time . This means that neologisms are overall more likely to spread successfully if their use is not limited to a centralized network of speakers in their early stages. Among the selected cases presented above, upskill fits this pattern: it shows a consistent, successful trajectory of diffusion and its use has been the product of a decentralized bunch of users since its early attestations. Of course, the diverging pathways of diffusion for other words such as hyperlocal and solopreneur presented in The dataset shows a significant correlation between the network structure in the first period of diffusion and the overall success of neologisms. Correlating In this paper, I have studied the spread of neologisms on Twitter to provide a multi-layered picture of the diffusion of lexical innovations in terms of 1) overall usage frequency, 2) changes in usage frequency over time (volatility), and 3) pathways of social diffusion across members and networks in a larger speech community. The process of diffusion entails social processes which lead to the spread of innovations in social networks . Theorettweeter, smartwatch), medium , and low degrees of diffusion . However, differences in the temporal dynamics of use have proved to be necessary for a more accurate assessment of the degrees and pathways of diffusion of neologisms.The frequency-based approach revealed that frequency measures can be used to assess degrees of diffusion of lexical innovations with varying success. Total frequency counts –4 provedlexical innovation, this temporal sensitivity is not surprising. Models of linguistic diffusion such as the S-curve model assume competition processes in which several formal variants compete to become the conventional linguistic means to express a certain meaning/function in the speech community. In cases of grammatical innovation, which is at the core of most models and most previous empirical investigations of diffusion, the communicative need for expressing the target concept/function remains stable over time. While grammatical means are, of course, also subject to language change , the salience of the target semasiological space , remains stable over time for all speakers in the speech community. Both the direct competition between linguistic variants and the social and temporal invariance of the conceptual space over time are tacit assumptions of S-curve models of diffusion  typically show higher degrees of social diffusion than younger neologisms whose use almost exclusively goes back to a short period of highly intensive use . The positive relationship between the age of neologisms and their degrees of diffusion was supported by the significant correlation with centrality in the network analysis. While a longitudinal, predictive approach to the fate of lexical innovations is beyond the scope of the present paper, it seems possible that neologisms follow Lindy’s Law: the longer new words have been in use in the speech community, the less likely they are to become obsolete in the (near) future  future . The fathyperlocal, upskill), most exhibit considerable fluctuations. For some words in the sample, recurrent spikes in usage intensity are an inherent part of their usage profile. The neologism youthquake is characterised by spikes in usage intensity when relevant to current public affairs, but shows low frequency of use in the intermediate intervals. Due to the nature of this behaviour, this pattern has been termed ‘topical’ by poppygate, for which these topical spikes occur in fairly regular, periodic intervals, have been classified as ‘recurrent semi-conventionalization’ by Lastly, the results showed that volatility in use is an important factor in the diffusion of neologisms. While some candidates show fairly consistent usage frequency over time , political communities , and/or highly volatile neologisms . A closer analysis of these cases in The more detailed evaluation of both approaches in These discrepancies in results reflect two perspective on the process diffusion. Successful diffusion of neologisms was defined as spread to new speakers and new communities. Using the frequency of occurrence of a neologism in a corpus to approximate to what degree it is familiar to bigger parts of the speech community thus has to rely on several assumptions which are only accurate to a certain extent.solopreneur) rather than moderate use by a higher number of speakers .Firstly, the number of uses observed might diverge from the number of speakers who are familiar with the term. Frequency can overestimate the latter, for example, if the observed use is the product of high usage intensity by a smaller number of speakers  conventional among the speech community. It is therefore to be expected that their use is unevenly distributed across communities of speakers. Since frequency counts alone do not provide information about this distribution, sociolinguistic data are needed to assess the degrees of social diffusion of linguistic innovations.Firstly, linguistic lexical innovations are often consciously coined and have a very specific communicative function. Their usefulness is closely tied to the conceptual salience of the entity they denote. The semantic carrying capacity of new words is thus much more likely to exhibit social and temporal variation than the functional potential of grammatical constructions. While speakers of English from all walks of life have felt the urge to talk about the future, the urge to talk about the future of ‘blockchain’ has only come up very recently, is (still) limited to specific parts of the speech community, and might not persist in the future. In other words, the use of lexical innovations exhibits greater social and temporal variation than innovations in other linguistic domains. The interpretation of aggregated frequency counts, which suggest a uniform distribution of use across time and across the speech community, is thus particularly problematic for assessing the diffusion of new words.Secondly, unlike linguistic innovations in other domains such as morphology or syntax, fleek, lituation) and political discourse , for example. A term like alt-left, which could in principle be used neutrally to designate the political far-left, is highly socially indexical of the far-right community it emerged from. Therefore it is less likely to be used by speakers outside this community, unless they are willing to be associated with this community. Neologisms which are socially indexical are thus more community-specific. Even when speakers outside this community are familiar with these terms, they are less likely to use them. Usage frequency counts miss such effects, since they only capture active uses of neologisms.Moreover, neologisms typically arise in specific communities of practice and often show, at least initially, high degrees of social indexicality with regard to these communities. The present dataset includes several neologisms which are associated with youth language (In summary, the present study has shown that frequency and network-based approaches capture different kinds of information about the use and spread of new words. As we have seen, both approaches show considerable overlap in their overall assessment of degrees of diffusion. On the one hand, measures which are based on the occurrence of neologisms in the corpus such as frequency, age, and volatility capture important aspects about the temporal usage profiles of neologisms. On the other hand, social networks provide a more differentiated view of the social dynamics of diffusion. They allow to visualise and quantify different pathways and degrees of diffusion, which enables a more detailed analysis of the spread of new words to new speakers and communities. While the approaches differ in their strengths and weaknesses, combining information from both approaches provides the most complete picture of diffusion, of course. In corpus-linguistic practice, total frequency counts are the most readily available and most widely used measure for the conventionality of linguistic constructions. The present results suggest that the additional consideration of temporal dynamics of use and social network information can contribute substantially towards a more detailed and accurate picture of diffusion.As I have argued, the use of network information is of particular importance for the study of neologisms, due to the nature of the process of lexical innovation. However, social network analysis also has great potential for sociolinguistic research in other domains. One of its biggest advantages is that it is usage-based and captures the communicative behaviour of speakers in interaction. It thus enables very fine-grained analyses of the sociolinguistic dynamics of communities, which can be visualised and qualitatively inspected on the basis of network graphs. Additionally, network science offers powerful algorithms to quantify and model the social characteristics of communities on a macro level.The interactional dynamics discovered by network analyses can be a valuable addition to more traditional, static sociolinguistic information such as metadata about groups of speakers. Moreover, network analyses can be used in cases where metadata about speakers are unavailable, as in the present study. Since the importance of online social networks like Twitter and Reddit is only going to grow in the future, both in terms of their role in society and in academic research, network analyses have great potential for future sociolinguistic research.


The study of the contribution of spatial transformation skills to driving behavior is a research topic substantiated by scarce evidence. In previous studies, we found that mental rotation and perspective-taking skills have an influence on performance in driving tasks by conveying the distal effects of the general cognitive efficiency on the execution of driving maneuvers. Studies have provided evidence on the relevance of the cognitive processes of encoding, imagined rotation, and spatial orientation in the accuracy of both the vehicle management during stressful driving situations and the acquisition of visual information on the traffic scenario. Results can find applications in both the training and the assessment of fitness to drive, as well as in the study of interaction between the drivers and in-vehicle devices. The lack of cross-validations in path analysis models cannot be assumed, a priori, to be capitalizing on chance and as an example of bad science. The non-replicability of a study should be demonstrated before it is proclaimed. The purpose of this reply was to address the questions raised by Kelly et al. (2022)—that is, “Do these results seem replicable?” and “How do these results advance our understanding of brain function and/or human behavior?”—by providing additional information on the study in question. The studies commented upon by Kelly et al. (2022)  presenteThe above-mentioned project deals with the study of cognitive  and personality determinants of fitness to drive (FtD). The project also includes an investigation of clinical samples that are not the object of the commented-upon study/studies. Both studies employed the same measures of general cognitive status (MoCA), mental rotation (MRT), perspective taking (PT), and the prerequisites of fitness to drive . The earlier work  investigInstead, the second work  examinedThe purpose of this report was to address the questions raised by Kelly et al. (2022) : “Do theThe term HARKing (hypothesizing after the results are known) generally indicates the strategy of presenting an a posteriori hypothesis as if it were predetermined . In his Following these definitions, the first type of HARKing practice assumes that hypotheses must be constructed when results are well known. In our publication history, the results of the first study became the starting point of the aim formulated in the second study , so no a posteriori hypotheses were stated.has been neglected” in driving research; see for instance [The second HARKing practice assumes that hypotheses must been formulated by retrieving them from an a posteriori bibliographic search. To the best of our knowledge, the study in question  is the finstance  (p. 260)The third kind of HARKing practice involves the omission of predetermined hypothesis that are unsupported by the obtained results. This practice implies that all the obtained results, or at least most of them, should have a perfect fit with the predetermined hypotheses. Conversely, few predetermined hypotheses reported in the study in question have been only partially supported by results. Therefore, in that study, not all hypotheses formulated have been corroborated by the results. In particular, (a) the mediated mediation of both the spatial skills was hypothesized to predict the resilience of attention and perceptual speed. Conversely, only mental rotation predicted the resilience of attention, while only perspective taking predicted the perceptual speed, both through single mediations. Moreover, it was hypothesized that (b) mental rotation would have showed a mediation role between the cognitive functioning and the reaction speed. Again, this hypothesis was not verified by the results. Finally, hypotheses on both (c) the negative effect of age on driving measures and (d) the positive effect of the MoCA expected on resilience of attention and perceptual speed only were formulated following results obtained in our first study, and they have been verified even in the second study. In this case, it is unclear how we would have practiced this third kind of HARKing, since only two out of four among the declared hypotheses have been found.According to Kelly et al., the studies “lack important details concerning selection of study participants, leading to puzzling discrepancies in the participant selection criteria for the two studies”. However, (a) the assumptions underlying each study differed, (b) the two studies concerned diverse age cohorts, and (c) there were different data collections at the base of the two studies . In both the studies, participants were required to (i) have Italian as their mother tongue, (ii) have a valid current driving license, provisional or above, (iii) have normal or corrected vision, and (iv) not being or had been a professional driver. The first study included five enrolment criteria, while the second had six. Both the studies were limited to a sample of (v) active drivers; however, while the former work included participants who have driven at least one time in the previous month, the second study included those who reported driving at least once in the previous week. These more restrictive constraints justify why the second paper involves only a quarter of the participants of study one. This discrepancy was the consequence of the different aims of the studies. The first study was completely explorative, while the second represented an attempt to find a more efficient and exhaustive explanation from the point of view of the structural relationships between variables through pathways models. The relationships between variables which emerged firstly in terms of statistical causal models, if further confirmed by studies of other groups/centers, might provide suggestions on the brain processes and on the circuits involved in supporting driving performance. To address the aim of the second study, we have chosen to limit the investigation to those drivers with a stronger driving experience, i.e., those most frequently exposed to driving activity in everyday life. As stated above, the sample of the second study involved only male participants aged from 18 to 91 years. The samples of the two studies differed because the second included only males and older drivers.The group of women drivers was excluded in the second study, since few of them (adult and older) met the enrolment criteria. The same reason explains why three male participants were excluded. Anyway, most of female drivers included in the first study reported driving two or three times in the previous month. This may be the consequence of the cultural trends in driving activity for older women in our geographic/cultural area. Despite the continuous increase in the number of older women behind the wheel , they reNevertheless, the decision to restrict the investigation to male drivers was made to avoid discrepancies between (1) the gender group sizes and (2) the distribution of age within the gender groups. In other words, this was an attempt to avoid capitalizing on the previous data collection. Finally, the fact that a “convenience sample” was included in the second study had been clearly reported as a limitation in the paper.To consider active drivers, those who drive at least once a week or once a month (or in the last week/last month) is a well-consolidated stance in driving research ,12,13. FFour out of the five enrolment criteria were the same among the studies. Considering the methodological reasons supporting the choice, to both modify and add an extra criterion in the second study, such discrepancies may perhaps seem less “puzzling” now.Kelly and colleagues pointed out some statistical limitations regarding path analyses, structural equation modelling, and factor analyses. These issues limit the replicability of the results in path analysis as, potentially, in any multivariate statistical technique. We are also aware of solutions such as that indicated in the commentary, and that the sample size does not always allow for cross-validations. The suggestions described by Kelly and colleagues are useful and widely used methods to avoid these statistical limitations. Even in this case, this issue was listed among the limitations, where the need to replicate the studied model on a larger and more representative sample of drivers was clearly pointed out. With an awareness of the limitations due to statistics-related methods, and in turn to the generalization of results, the study provided tentative evidence on the structural relationships between the employed variables. The fact that the study pointed out early, weak, and limited evidence of statistical mediation among these variables itself is not enough to consider it to be an example of bad science. A plethora of studies used similar statistics (some of which inspired our work) and provided in the same way evidence of mediated effects. Indeed, all the studies providing early evidence of a relationship between variables without cross-validating it might be assumed to be capitalizing on chance, and could be pointed to as examples of bad science. This is a radical—somewhat Manichean—vision of research, in our opinion. Certainly, all statistical models are approximations. Anyway, following the famous statistician George Box, we could affirm that “all models are wrong, but some are useful”. In this report, the potential usefulness of the studied model of mediation in driving research was highlighted by providing possible implications.Spatial perception, memory, and mental representation are a series of connected cognitive skills useful for driving. Specifically, both egocentric (self-to-object) and allocentric (object-to-object) spatial representations are assumed to be crucial when navigating by car by supporting the management of the vehicle as, for example, when we turn at an intersection, or we drive through a roundabout. This occurs thanks to the flexible alternation between the two kinds of spatial representation in a process known as spatial updating, underlying navigation by walking as well as by driving ,15,16. SUndoubtedly, this suggests the key role of spatial transformation skills in the execution of complex driving behaviors. Moreover, by relating both spatial transformation skills and cognitive functioning with driving measures, these results may be useful for the assessment of fitness to drive, the training of impaired driving abilities, and in studying the interaction between the driver and the in-vehicle systems. Since spatial transformation skills are key cognitive components of fitness to drive, these measures should be included in the assessment, and it could be the target of training programs for driving capability. In-vehicle systems aid the driver during navigation and in detecting visual scenarios beyond their own visual field. Advanced driver-assistance systems support and facilitate complex maneuvers, such as overtaking or parking. Sensors, cameras, and monitors detect and display the driving scenario out of the driver’s visual field, helping to minimize errors during the maneuver. Mental rotation and perspective-taking abilities are involved in both the visualization and decoding of the spatial relations provided by these devices from the displayed perspective. The study of spatial transformation skills may help researchers to better understand the driver’s interaction with these devices. However, further research is needed to assess whether spatial transformation skills contribute to the readability of the spatial information provided by these systems.Following Kelly et al., that the MoCA and spatial skills correlate to some degree with the significant indirect effects of spatial skills is not surprising. Certainly, the results could be explained with reference to shared visuospatial processes that are involved in the employed measures. This explanation was put forward frequently in the discussion of the results. Anyway, what surprises us is that both the spatial skills seem to work better if they are considered to be mediators in the model, rather than if they are considered to be predictors. It should be noted that among the theoretical assumptions of the statistical mediation, the association between the independent variable and the mediator is mandatory ,17. As rIn fact, what we found suggests that the relationship between global cognitive functioning and certain driving abilities is mostly a matter of spatial transformation skills.As stated above, the research project including the commented-upon study/studies also involves the investigations on a clinical sample of drivers. For this reason, the MoCA test was employed among the test set. Moreover, the employment of the MoCA as a measure of general cognitive efficiency needs further clarifications. First, the considered non-pathological range for the MoCA total score included 12 points . Second, the distribution of the MoCA scores deviated from normality, but measures of skewness |0.195|) and kurtosis (|0.579|) did not exceed critical thresholds 5| and ku. As suggFor the same purposes, the MoCA total score had been used as a measure of “global cognitive functioning” or “cognitive screening” in other studies , includiThe case of the apparent association between two variables that is reversed when the analysis is performed by considering a third confounding variable is known as Simpson’s paradox . The risFinally, in response to questions of Kelly et al., it could be useful to clarify that (i) the MoCA was not used to define clinical samples, but as measure of general cognitive functioning, and (ii) the study did not aim to investigate comparisons between healthy and cognitively impaired people. Of course, the employment of the MoCA in the assessment of FtD would be better suited for studying older drivers’ driving abilities than those of the young and adults. In these studies, we were interested in investigating the driving abilities of drivers in age stages which preceded the explicit cognitive impairment. The study of driving fitness in participants with cognitive impairment remains an open issue in driving research that needs exhaustive investigations, but it was not the aim of our paper(s).


Mustela putorius furo, is an important animal model in neurodevelopment for its complex postnatal cortical folding, its long period of forebrain development and its accessibility to genetic manipulation in vivo. Here, we discuss the molecular, cellular, and histological features that make this small gyrencephalic carnivore a suitable animal model to study the physiological and pathological mechanisms for the development of an expanded neocortex. We particularly focus on the mechanisms of neural stem cell proliferation, neuronal differentiation, cortical folding, visual system development, and neurodevelopmental pathologies. We further discuss the technological advances that have enabled the genetic manipulation of the ferret in vivo. Finally, we compare the features of neocortex development in the ferret with those of other model organisms.The neocortex is the largest part of the cerebral cortex and a key structure involved in human behavior and cognition. Comparison of neocortex development across mammals reveals that the proliferative capacity of neural stem and progenitor cells and the length of the neurogenic period are essential for regulating neocortex size and complexity, which in turn are thought to be instrumental for the increased cognitive abilities in humans. The domesticated ferret,  Mustela putorius furo) is a small carnivore, domesticated more than 2000 years ago  30, ferret is a suitable model system for studying the early development of the visual system and the role of sensory experience therein , protract into the first weeks of postnatal life . From a  therein .Third, the ferret is an established model organism for various human pathological conditions, as it shows similarities not only with the human neurodevelopment, but also with the human immune response . Thus, iThe ferret has been used in research for more than 100 years  and it eThe mammalian neocortex develops from the dorsolateral part of the telencephalon at the rostral-most part of the neural tube . At veryNewborn projection neurons migrate from the site of their origin in the germinal zones to their final destination in the CP using the radial processes of radial glia . The mamAlthough the neocortex is present in all mammals, its size has been subjected to evolutionary differences within various mammalian orders . For exaAn increase in neuronal production is thought to be the key factor underlying the evolutionary expansion of the neocortex. Such increase is a consequence of the increased proliferative capacity of neural progenitor cells and the resulting extension of the neurogenic period . Among tBasal progenitors can generally be divided into two subclasses: basal intermediate progenitors (bIPs) and basal radial glia , with the latter being particularly instrumental for the neocortical expansion . bRG shoThe prolonged neurogenesis has been suggested to be a consequence of a higher proliferative rate of BPs in animals with an enlarged neocortex. Whereas neurogenesis in mouse lasts ∼9 days, in primates it is 10 times longer and in ferrets it proceeds for ∼5 weeks . The lenFerret SP neurons are generated between the embryonic day (E) 20 and E27 , whereasDuring its embryonic development, the ferret contains all the histological and cell biological features required to build an expanded neocortex . First, Ferret gliogenesis starts during the last 4 days of the embryonic development (E38–E41) concomitantly with the peak of neurogenesis . SimilarSimilar to the onset of neurogenesis, the termination of neuronal production follows rostro-caudal and latero-medial gradients. Whereas in the prospective somatosensory cortex production of neurons is largely completed at birth, in the visual cortex neurogenesis was reported to protract for 2 weeks postnatally . NeuronaSynaptogenesis in the ferret starts as soon as migrating neurons reach their final position in the CP . SynaptoThe ferret is born lissencephalic, that is with a smooth brain, and the folding process takes place during the first month of life . The firThe ferret is an important model organism for studying the development of cortical areas and circuitry. In particular, the ferret gave an important contribution to our understanding of the development and maturation of sensory processing . This isFerret frontal cortex lies in the anterior sigmoid, posterior sigmoid, proreal and the orbital gyri at the most rostral part of the brain . Contrarin utero  germline knockout ferret line to model human microcephaly. The knockout was achieved by Transcription Activator Like Effector Nucleases (TALEN)-mediated genome editing. A year later, Whereas local, acute genetic manipulation methods have been successfully adapted to ferrets and can now be routinely used, there are only a couple of examples reporting the generation of transgenic ferret lines. Owing to the emergence of new techniques, notably those that render the ferret a genetically accessible model organism, it is now possible to use ferrets to study the pathophysiology of various diseases. This is most evident when focusing on neurodevelopmental defects and malformations for which other animal models, such as the mouse, have shown to exhibit limitations. The ferret has been used as a laboratory animal since the beginning of the 20th century, firstly to describe in details its embryology . It was The ferret is a well-established animal model to study the symptomatology, transmission and immune response related to respiratory viruses, notably influenza viruses . MoreoveCFTR (cystic fibrosis transmembrane conductance regulator) and characterized by chronic infection, inflammation, and mucus obstruction , lissencephaly , polymicrogyria , dysplasia , and heterotopias , are linked to various intellectual or motor disabilities .Aspm   . The Asphickness .CDK5 (cyclin-dependent kinase 5) gene  gene . Studiesexplored . In contmisphere .Cortical dysplasia is a neurodevelopmental defect caused by impaired neuronal migration and it is associated with epilepsy and mental retardation. The generation of a ferret model for cortical dysplasia was achieved by injection of the anti-mitotic drug methylazoxymethanol . The treFGFR3 (fibroblast growth factor receptor 3), which cause a constitutive activity of the receptor  is a severe genetic skeletal dysplasia that results from missense mutations in receptor . The cerreceptor . A ferrer of BPs . Importar of BPs , perivenr of BPs , and lepr of BPs .Hydrocephalus is a condition in which excess cerebrospinal fluid accumulates within the ventricles of the brain. In light of the characteristic postnatal protraction of the ferret neurodevelopment, ferret kits at P14 have been used as a model system for the post-hemorrhagic hydrocephalus, which is associated with premature birth . To induFerrets contain a higher white matter content than rodents, similarly to humans . This leConsidering that the degree of maturation of the ferret brain at the moment of birth is similar to that of humans during the last trimester of pregnancy, ferret kits are also used to model preterm and perinatal human brain injury. This model was generated by subjecting the ferret kits to sub-lethal, chronic hypoxia from P10 to P20, which increased astrocytosis and decreased myelination, similar to human patients .Here we discuss the possibilities and limitations of using the ferret as a model organism for neurodevelopment. We mainly compare ferrets with the other major mammalian model organisms, notably rodents and primates. We particularly focus on the suitability of ferret as an animal model for brain evolution, brain development and neurodevelopmental pathologies.Aedes aegypti that has become a neurobiological animal model. In light of those steps, we here discuss the advantages and limitations of using the ferret as a neurodevelopmental model organism.A plethora of different factors contributes to determine what makes a good model organism. In the past three decades, the mouse has risen as a principal model organism in many biological disciplines, including developmental neurobiology, largely due to its unparalleled genetic accessibility . Howeverin utero and postnatal electroporations as well as viral injections opened the possibility to introduce genetic manipulation acutely during development (in utero electroporation was achieved. Fifth, transgenic ferrets are now available (First, the ferret is a highly suitable and interesting model organism for studying brain evolution, brain development and the related pathologies. As discussed in detail in the following sections, ferrets are more than rodents, but less than primates, similar to humans, in most of the above-mentioned aspects. Second, the ferret has been domesticated for more than 2000 years and used as a laboratory animal for more than a 100 years . Ferretselopment . In thisvailable . Moreovevailable , routinevailable  and knocvailable , introduvailable , optogenvailable  and otheAs recently argued by Gilles Laurent, neuroscience has massively benefited from model system diversity and should further embrace comparative and evolutionary approaches in modern brain research . The ferThe enlargement of the neocortex does not concern only its surface area, although this is a dominant trait, but also its thickness . During Neocortex expansion is characterized by a differential growth of existing neocortical areas as well as the acquisition of novel ones, which in primate brain evolution is particularly relevant in the frontal cortex . The proin utero. Therefore, thanks to this practical and convenient feature of its neurodevelopment, the ferret rose to one of the principal models for studying cell biology in vivo of neural stem cells, neuronal migration and connectivity. For example, the ferret is a good model to address the maturation of the thalamocortical connectivity in an extra-uterine context (Traditionally the greatest value of the ferret as a model system for brain development came from the characteristic protraction of its brain development into the postnatal period. This allowed researchers to study processes in ferret kits that in human and rodents happen  context . It has  context .The second important feature of ferret neurodevelopment is its similarity to the human, especially when looking into neocortex development. This is most obvious when comparing mouse, ferret and human neocortex  developmDuring the neocortical neurogenesis the temporal order of neuronal production follows the well-established inside-out rule. Classical research in the ferret has provided important evidence that the potential of neural progenitors to generate lower vs. upper layer neurons is restricted over time . Upon heIn light of the above-mentioned developmental features, the ferret is considered to be a highly suitable model organism for certain neurodevelopmental pathologies. This primarily refers to neocortical malformations , which cThe ferret is a suitable model for studying some of the mechanisms regulating brain development, but it also exhibits certain limitations. Only some molecular and cellular mechanisms involved in neocortex development and the related pathologies are conserved across mammals and this is particularly relevant for the development of complex traits. For example, neocortical folding is thought to arise through an interplay of genetic and mechanical factors , with soin utero, which can lead to a different development and maturation of cortical sensory areas. An example is the difference in some aspects of maturation of the visual circuitry, which are thought to happen in a hierarchical fashion in humans, but occur in a synchronous manner in ferrets (The protracted postnatal period of brain development has traditionally been one of the greatest reasons for using the ferret kits to model the last trimester of human brain development , however ferrets .Finally, there are ethical considerations to take into account, especially when working with transgenic ferrets. Research involving ferrets is usually subjected to a greater regulatory scrutiny than the one involving mice. In contrast, ferrets could be a suitable replacement for primates when studying developmental mechanisms that are pertinent to all species with an expanded neocortex. Hence, the ethical considerations, along with the space allocation and cost of ferret research, are additional limitations for using ferrets instead of mice, but at the same time provide an advantage for using ferrets as a replacement for primates.Ferrets are fascinating creatures whose neurodevelopmental features render them an important model organism for brain evolution, development, and related pathologies. In this review we highlight the key characteristics of the developing ferret neocortex and discuss the tools and techniques that enable us to use these animals for revealing the complexity of the mammalian neocortex development and modeling human neurodevelopmental pathologies.Both authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.