Humanitarian emergencies, including complex emergencies associated with fragile states or areas of conflict, affect millions of persons worldwide. Such emergencies threaten global health security and have complicated but predictable effects on public health. The Centers for Disease Control and Prevention (CDC) Emergency Response and Recovery Branch (ERRB)  contributes to public health emergency responses by providing epidemiologic support for humanitarian health interventions. To capture the extent of this emergency response work for the past decade, we conducted a retrospective review of ERRB’s responses during 2007–2016. Responses were conducted across the world and in collaboration with national and international partners. Lessons from this work include the need to develop epidemiologic tools for use in resource-limited contexts, build local capacity for response and health systems recovery, and adapt responses to changing public health threats in fragile states. Through ERRB’s multisector expertise and ability to respond quickly, CDC guides humanitarian response to protect emergency-affected populations. The number of persons affected by humanitarian emergencies worldwide is unprecedented; in 2016, the United Nations Office for the Coordination of Humanitarian Affairs estimated that 125 million persons needed humanitarian assistance  (4).>10-fold above baseline rates  has long been a leader in developing and understanding the epidemiology and public health effects of humanitarian emergencies and CEs specifically. CDC’s work in CEs began during the 1968 war-induced famine in Biafra in West Africa, during which staff documented the extent of severe malnutrition , in the Division of Global Health Protection, Center for Global Health. ERRB includes the Global Disease Detection Operations Center, the Global Rapid Response Team, the Global Response Preparedness Team, the Global WASH Team, and the Humanitarian Health Team, thus unifying CDC’s humanitarian emergency preparedness, alert, and response activities into a single program. Staff members work with the international humanitarian community to apply public health and epidemiologic science, develop tools and methods to understand health needs, and build the capacity and resilience of public health systems within these fragile settings. This article focuses on ERRB’s work in humanitarian emergency response over the past decade; its collaboration with response partners; the broad lessons that can be drawn from its work; and how it and other humanitarian health responders are adapting to address new threats to global health security, new needs of populations affected by CEs, and humanitarian emergencies at large.http://cedat.be) and the United Nations Office for the Coordination of Humanitarian Affairs Central Emergency Response Fund archives of funded responses . Included events were those that affected >10,000 persons and had a documented CMR of >1 death/10,000 persons/day. Sources for natural disasters were the Center for Research on the Epidemiology of Disasters international disaster database (http://www.emdat.be) and Central Emergency Response Fund archives; inclusion required that the event affected >10,000 persons. To compile emergency responses for 2015 and 2016, we abstracted data from branch administrative and travel records. Responses were selected to reflect >1 response/year and to include those in which branch staff had a major role.We retrospectively examined ERRB responses during 2007‒2016. To compile the responses that occurred during 2007‒2014, we abstracted data from past branch activities databases and publications. To ensure the completeness of this dataset, we compared it with a previously compiled comprehensive database of all emergencies worldwide, including CEs and natural disasters, for the same period . Sources of CEs included in this database were the Center for Research on the Epidemiology of Disasters Complex Emergency Database  , which led to identification of measles outbreaks in 2 refugee camps. Staff review of demographic profiles of outbreak cases led to an expansion of the target age group for vaccination from 6 months–14 years of age to 6 months–30 years of age  to strengthen its Health Information System (HIS) disease surveillance ; UN agencies, including the World Health Organization, UNHCR, and UNICEF; and national and international NGOs. At a basic level, these close relationships allow ERRB and other humanitarian responders access to CE settings. These collaborations encourage standardization of approaches across the international humanitarian emergency response community (http://smartmethodology.org/survey-planning-tools/smart-emergency-nutrition-assessment) and led the technical development of the Community-based Management of Acute Malnutrition report for monitoring programs to manage malnutrition in emergencies . In the sexual and gender-based violence sector, branch staff contributed to the guidelines for integrating gender-based violence interventions in humanitarian action (http://gbvguidelines.org/wp/wp-content/uploads/2015/09/2015-IASC-Gender-based-Violence-Guidelines_lo-res.pdf). Across these and other sectors, in settings where the evidence base for interventions is limited, CDC focuses on strengthening the accuracy of data to build a solid evidence base for interventions to guide humanitarian response, enhance global health security, and prevent morbidity and mortality.Second, because public health emergency responses often take place within the context of mass population displacement and fragile states, CDC and other responders must develop and apply epidemiologic methods and tools to be used in challenging and resource-limited settings. ERRB has contributed to several such tools. In the nutrition sector, ERRB enhanced the application of the emergency nutrition assessment software that facilitates survey planning, data collection, and analysis of anthropometric indices (Third, effective emergency responses must adapt to changing needs of emergency-affected populations. Humanitarian emergencies, especially CEs, which exacerbate the fragility of politically weak and unstable regions, could last several years without a clear endpoint. Although dramatically elevated mortality rates might decrease as a CE moves from an acute emergency to a postemergency phase, populations continue to be vulnerable to many of the same health risks. As the humanitarian response evolves and becomes better established, responders might need to strengthen disease surveillance, review and interpret public health data, and improve capacity of local or national public health systems. Responders must maintain a commitment to improving the function and resilience of public health systems within these fragile settings.Fourth, ERRB’s work supports the work of CDC to prevent, detect, and respond to public health threats in fragile states under conditions that can result in regionally destabilizing effects and threaten global health security. Responding effectively requires that ERRB and other responders recognize 3 global patterns in population displacement: urbanization of the displaced, a shifting disease burden that includes noncommunicable diseases, and increasing security restrictions in areas of displacement. Understanding the unique aspects of urbanization of the displaced, moving away from the rural camp–based models of the past, suggests the need to change epidemiologic methods of surveillance and population assessment. In addition, because the displaced are increasingly likely to need assistance for noncommunicable, chronic diseases and access to long-term health services, compared with displaced populations in the past (Finally, ERRB responses show that response expertise is most useful when deployed early in an emergency and with a sustained presence. To that end, ERRB’s Global Rapid Response Team quickly matches needs in the field with expertise available from within ERRB and across the entire CDC, and these responders can provide longer-term support. In its first year of existence, the Global Rapid Response Team deployed >200 staff members to various emergency responses, including for Hurricane Matthew in Haiti in October 2016.As the numbers affected by and intensity of humanitarian emergencies increase, ERRB and other response organizations must provide broader assistance. To that end, ERRB collaborates with partners; contributes to epidemiologic tools to be used in humanitarian emergencies; and, through the Global Rapid Response Team, responds more quickly and with more staff. The next steps for ERRB and other responders include improving capacity and resilience of public health systems in fragile states; understanding the public health implications of long-term, urban-based displacements; adding a focus on noncommunicable diseases; and providing remote epidemiologic support in a systematic way. In settings where ERRB staff, as representatives of a US government agency, cannot respond, CDC’s evidence-based interventions for emergencies are still implemented because of branch efforts in building local capacity for emergency response and training public health practitioners who then move on to work with humanitarian agencies. In these ways, ERRB continues to apply public health science to save lives in humanitarian settings while also working on the forefront of response-purposed detection and preparing a global health response workforce.Select Centers for Disease Control and Prevention Emergency Response and Recovery Branch humanitarian emergency responses conducted, by year, type of emergency, activity, and partner, 2007–2016.


Subtropical reefs provide an important habitat for flora and fauna, and proper monitoring is required for conservation. Monitoring these exposed and submerged reefs is challenging and available resources are limited. Citizen science is increasing in momentum, as an applied research tool and in the variety of monitoring approaches adopted. This paper aims to demonstrate an ecological assessment and mapping approach that incorporates both top-down (volunteer marine scientists) and bottom-up (divers/community) engagement aspects of citizen science, applied at a subtropical reef at Point Lookout, Southeast Queensland, Australia. Marine scientists trained fifty citizen scientists in survey techniques that included mapping of habitat features, recording of substrate, fish and invertebrate composition, and quantifying impacts . In 2014 these volunteers conducted four seasonal surveys along semi-permanent transects, at five sites, across three reefs. The project presented is a model on how citizen science can be conducted in a marine environment through collaboration of volunteer researchers, non-researchers and local marine authorities. Significant differences in coral and algal cover were observed among the three sites, while fluctuations in algal cover were also observed seasonally. Differences in fish assemblages were apparent among sites and seasons, with subtropical fish groups observed more commonly in colder seasons. The least physical damage occurred in the most exposed sites (Flat Rock) within the highly protected marine park zones. The broad range of data collected through this top-down/bottom-up approach to citizen science exemplifies the projects’ value and application for identifying ecosystem trends or patterns. The results of the project support natural resource and marine park management, providing a valuable contribution to existing scientific knowledge and the conservation of local reefs. Marine environments, particularly near-shore reefs, are under severe threat from human impacts –3. HowevVolunteer participation has become an increasingly significant component of ecological research projects, particularly where high levels of observation effort are typically required to assess biodiversity, or to understand temporal and spatial community dynamics –12. CitiThe involvement, skills and knowledge required of volunteers in marine and coastal citizen science projects varies, ranging from projects that use minimal training of volunteers, to training-intensive projects. For example, CoralWatch provides a simple approach that does not require specific SCUBA training as it can be done walking, by snorkel and/or on SCUBA to undertake surveys , 13. RCAThe organisation of citizen science projects typically involves either a top-down or bottom-up approach . A top-dWhile concerns have been raised about the quality and compatibility of data collected by volunteers –21, citiSubtropical reefs occur around the world in bio-geographical transition zones from tropical to temperate regions . HistoriStegostoma fasciatum) ..44].Flat Rock was the furthest from shore and covered the largest area (~65 Ha), followed by Shag Rock (~12 Ha) and Manta Ray Bommie (~4 Ha). The deepest water was found near Flat rock (35 m), followed by Shag Rock (18 m) and Manta Ray Bommie (16 m).Differences between sites and seasons for the benthic cover were assessed using a PERMANOVA analysis with Bray-Curtis distances and 999 permutations. The assumption of homogeneity of dispersion (permdisp) was met for both factors and significant effects were found for both sites  and seasons . Post-hoc pairwise tests showed that the variation in sites was significant between Flat Rock East and Shag Rock East  primarily due to a higher proportion of turf substrate at Shag Rock East . Additionally, variation was significant between Flat Rock East and Manta Ray Bommie  primarily driven by a higher proportion of hard coral at Flat Rock East and non-living substrate at Manta Ray Bommie. Marginal significance was found between Flat Rock West and Shag Rock West  with the former site having a higher proportion of algae. The major variation in seasons was between spring with both summer  and winter  primarily driven by a higher proportion of turf in summer and winter.The five transects  varied iLobophora, Asparagopsis and Laurencia) and turf algae accounted for the highest percentage cover (>50%) of the substrate types at all sites  and Manta Ray Bommie (1.2%) respectively. Interestingly, fluctuations in algal cover were observed seasonally , while turf algae coverage remained constant at all sites, over the year  urchins were the most common and were observed with significantly greater frequency at the Shag Rock sites than at the other sites , giant clams (Tridacna spp.) and lobsters (Panulirus spp.) were rare, averaging abundances of <1 per 100m2 at all sites, whilst indicator sea cucumbers, Trochus niloticus and Triton shells were not observed at any sites (data not shown).Banded coral shrimp (Drupella snails and unknown causes), coral disease, physical damage and rubbish were recorded consistently at both Shag Rock, and both Flat Rock locations .All five sites exhibited a diversity of fish families and species , with daVariation was observed seasonally with subtropical fish groups observed more commonly in colder seasons, whilst tropical groups such as parrotfish were comparatively rare year-round .Seasonal changes were apparent for the different trophic groups of fish. Herbivores and invertivores were observed primarily in summer and autumn .Although the project was based upon a 2001 ecological baseline assessment of the same area, methods have improved. Additionally, the 2001 data is potentially out-dated due to natural or anthropogenic impacts. The major improvements incorporated into the current project included more detailed training of the survey volunteers, RCA protocols were followed to record an increased number of invertebrate and reef impact indicators, coral health data was documented based upon CoralWatch protocols, and the capability for underwater digital photography enabled georeferenced photo surveys for benthic assessment and habitat mapping.The substrate data showed spatial differences between habitats on the different subtropical reefs. Each of the transect sites are subject to discrete exposure regimes and are located different distances from shore, leading to varying conditions at small spatial scales (hundreds to thousands of metres). Such variability is almost never quantified by scientific studies, which tend to examine assemblage processes at spatial scales of tens of kilometres or more .Lobophora) changed little over time, seasonal variations in algae composition were observed for less prevalent algal types (Asparagopsis and Laurencia).Shag Rock, Flat Rock and Manta Ray Bommie exhibited very different benthic characteristics, both within and among sites. For example, Flat Rock East exhibited high levels of coral cover compared to other sites, especially encrusting coral, reflecting its greater exposure to waves and wind. In contrast, Manta Ray Bommie exhibited the lowest level of coral cover and the highest abundance of non-living material, such as rock and sand. Although the abundance of the dominant algal types  that the discarded fishing materials date from pre-2012. Manta Ray Bommie, a site that is open to fishing, exhibited zero physical damage to coral, reflecting the largely sandy and rocky substrate and low coral cover. However, volunteer divers recorded larger quantities of discarded fishing material at Manta Ray Bommie than at the other two sites.The environmental conditions  varied during the surveys due to normal weather patterns, which would influence both the flora and fauna present and the ability of divers to observe particular species. Certainly, both visibility and currents varied and will have contributed to intra-season differences. Hence, ongoing seasonal surveys are valuable to distinguish between real seasonal change and observer error, and would provide us with a greater knowledge of what species are present or absent at different times of the year.Whilst a high number of volunteers were imperative for successful data collection at the scale proposed, this does present potential issues regarding the reliability of collated data . FoObserver error in volunteer data is probably most important to consider for fish because of their transient behaviour, giving volunteers less time to identify and count them correctly. Repeated seasonal surveys, and perhaps comparisons with expert data, will be required to confirm our fish results. Surveys where photos can be taken such as for substrate and reef impacts, offer additional opportunities for data validation as it is then possible to incorporate post survey data checking processes for quality control.Due to the large number of volunteers involved in the project and the challenges with making notes underwater, clarity of notes was not always consistent resulting in errors in post-survey data entry. Hence, it’s important to have: easy to use underwater datasheets; experienced and/or trained divers that can control their buoyancy; and data entry and validation soon after completion of the dives.This study demonstrated how citizen scientists can synthesize a broad range of marine ecological and spatial data by using an approach that incorporates both bottom-up (divers/community) and top-down (researchers) engagement aspects of citizen science. Volunteers were involved in all aspects of the project: applying for funding to support their citizen science project, conducting surveys, entering and quality-controlling data and publication. The results of this project add to the growing citizen science literature by demonstrating the type, quality and quantity of data that can be delivered when volunteers are provided with the tools, training and support to actively participate in ecological studies.Fine-scale ecological patterns on subtropical reefs were quantified at the target sites for the first time, enhancing the knowledge about these sites for managers, decision makers, and recreational users. The ecological assessment and analysis revealed that even reef sites in close proximity (hundreds to thousands of metres) could contain different microenvironments demonstrating a degree of habitat variation over small spatial scales. The differences in environments are potentially due to proximity to land, prevailing currents, swell and winds, in addition to other topological factors. The study further revealed that these microenvironments vary in composition over time, which may be explained by seasonal changes in environmental conditions on subtropical reefs , 49.Regular monitoring of local reefs would improve understanding of ecological changes and enable scientists and management agencies to better understand if these are due to natural variations or caused by external factors such as fishing, pollution or physical damage. The monitoring would provide data to support management decisions that would otherwise not be collected due to a lack of resources within local marine authorities, hence confirming the importance of citizen science.Citizen science is not just about utilising volunteers to collate scientific data. It is also about engaging the community to create awareness of the importance of the natural environment, to instil a sense of ownership and pride, and to promote co-learning opportunities about the need to maintain and conserve our ecosystems in the face of increasing pressures. The success of this citizen science project was highlighted through: the inclusion of the results and findings , 50 in rAdditional detail of the project can be found online in regards to: methods , report S1 Table(PDF)Click here for additional data file.


N = 13) with representation from Australia, Canada, Ireland, and the United States. Panel communication was predominantly conducted by email and occurred from November 2016 through February 2017. Expert panel work resulted in the generation of a work product: Qigong in Cancer Care Guidelines: A Working Paper including: (a) Consensus Guidelines for structure and delivery of Qigong exercise for Cancer care programming; (b) Consensus guidelines for instructor competence for teaching Qigong exercise for cancer care classes; (c) Screening tool for safe participation in Qigong exercise; (d) Class participant instructions for maintaining safety during Qigong exercise; and (e) Advice from the field. Generation of these resources is the first step in establishing recommendations for ‘best practice’ in the area of Qigong for cancer care programming.Integrative oncology, including Qigong, is a relatively new concept in modern healthcare. Evidence of benefits of Qigong in cancer survivors is emerging. As such, several cancer centers, world-wide, have introduced Qigong as part of integrative medicine within supportive cancer care programming. Qigong exercise programming content and quality varies among institutions due to lack of standard guidelines and, at present, relies solely on the instructor’s skills, knowledge, personal preferences and clinical experience. Development of consensus guidelines recommending the basic structure and delivery of Qigong programming in cancer care can potentiate quality assurance and reduce risk of harm. This applied qualitative research utilized a modified Delphi approach to formulate consensus guidelines. Guidelines were developed through discussions among an international expert panel ( Cancer is pandemic. There are an estimated 15 million cancer survivors in the United States . Qigong In China, Qigong exercise is widely practiced in management of cancer in conjunction with standard care. Applied theoretical research suggests that practice of Qigong exercise may also have a supportive role in cancer prevention and improved survival ,8,9. HowRecently, the Office of Cancer Complementary and Alternative Medicine of the National Cancer Institute (NCI) released proceedings from its Strategy Meeting for the Development of an International Consortium for Chinese Medicine . Among gAcupuncture consensus statements and guidelines for safe practice in cancer survivors have been developed by the National Institutes of Health (NIH) in USA  and in tThis applied qualitative research utilized a modified Delphi approach to formulate a consensus draft of best-practice guidelines for structure and delivery of complementary Qigong exercise in cancer care. An international expert panel of convenience was assembled to conduct the work. Panel communication was predominantly conducted by email and occurred from November 2016 through February 2017. Initially, draft guidelines were developed by a subcommittee of convening panel members. A full panel of experts was then assembled, and three rounds of panel discussion were initiated. In the first round, panel members independently reacted by comment to the draft guidelines. In the second round, panel members reacted to a collation of the independent panel comments generated from the first round. Then, an internal subcommittee, including the three originating members in collaboration with an additional panel member, serving as medical consultant, drafted revised guidelines reflecting and incorporating panel member comments from Rounds 1 and 2. In the third round, the proposed revised guidelines were circulated to poll level of panel member consensus. In planning study design, several factors were considered. A target panel size of 12 to 15 experts was set. Panel members were to include researchers as well as practitioners. Practice settings were limited to those consistent with a delivery model of modern Western medicine. A wide geographic representation was considered to be desirable. A list of potential panel members was generated from instructors listed with the National Qigong Association and the Qigong Institute websites who indicated interest in cancer as a clinical teaching area, identification of Qigong instructors affiliated with cancer centers listing Qigong or Tai chi classes as part of support programming, authors of published research, and nomination by panel members. By this process, 20 experts were identified and contacted regarding interest in joining the panel. Thirteen experts consented to participate.Three data gathering tools were employed in this study, a survey of panel demographics and existing program characteristics, a survey of agreement and comment on the draft guidelines, and a polling of consensus for the resultant revised guidelines.Panel Member Demographics Survey (and description of exiting programming) was administered in Round 1. This survey gathered information regarding panel composition by gender, age, geographic locale, credentials, research activity, Qigong/Tai chi training, years of practice, years of teaching, years teaching in Qigong in Cancer care programming, and descriptions of active Qigong in Cancer Care programming.The first survey, Review and Comment Survey (of draft guidelines), was also administered in Round 1. Draft guidelines were prefaced by a philosophy statement. They were organized into three major sections: Content (7 items), Instructor Competence (18 items), and Delivery Logistics (6 items). Panel members reacted by (a) level of agreement per each individual draft guideline, and (b) comments solicited by item and major section. Level of agreement for each of the 31 recommendations was assessed by a 4-point, Likert-like scale using the categories: strongly agree, agree, disagree, and strongly disagree. Comment solicitation was open-ended. The second survey, approve or disapprove of the work product in total with opportunity for additional comment.Final consensus polling occurred in Round 3. In this final round, a summary working paper including revised guidelines and three additional panel products was circulated. Polling of agreement was conducted by vote: This research was conducted with full IRB approval through D’Youville College, Buffalo, NY, USA and has been performed in accordance with the ethical standards as laid down in the 1964. Declaration of Helsinki and its later amendments or comparable ethical standards.Working Paper.Analyses were descriptive. Panel demographics and characteristics of existing programs were recorded and described for report presentation. Panel comments were categorized through thematic analyses. For determining consensus, a criterion of ≥80% approval of final products was set. Consensus products generated by this work were described as work products. Work products were then integrated into a summary The 13-member expert panel is described as follows. The panel included seven males and six females. Average age was 59.77 years (SD 7.143). There was international representation. Countries represented included Australia, Canada, Ireland, and the United States. Within the United States, members represented the Northeast, Southern Atlantic, Central, Midwestern and Western regions. Seven of the 13 members hold graduate academic degrees. Seven members have published research. Six members have published instructional books or DVD’s. Three hold clinical degrees including a doctor of Chinese Medicine, a medical doctor with additional certification in medical acupuncture, and a physiotherapist. Nine members were currently teaching in dedicated cancer-care. Five members professed intimate knowledge of the cancer experience. Two members were in active cancer treatment during the time the research was being conducted. One panel member withdrew during Round 2 discussions citing other commitments as reason for withdrawal.Mean years-of-practice was reported as 20.5 years . Mean years teaching was reported as 15.38 years (SD 9.5). Panel members have a collective total of 100 years experience teaching Qigong classes dedicated for cancer care. Member training and practice involves a wide range of styles and forms including Yang, Chen, Sun and other derivative Tai chi styles and various forms of Qigong and modern derivations of traditional Qigong. All members have training in more than one style and/or form. Two or more members have training in each of the following: 24 Posture Qigong (originated by Master Wang Ziping), eight Brocades (as taught by Dr. Yang Zwing Ming) ‘Moving for better balance’ (originated by Dr. Fuzong Li), Tai Chi for Arthritis (originated by Dr. Paul Lamb), Easy Qigong/Tai Chi™ (originated by Dr. Roger Janhke), and some variation of instruction in sitting Qigong/Tai chi. There was no formal training reported specific to teaching Qigong to individuals with cancer by any panel member.Class organization for existing Qigong exercise classes (N = 9) submitted by panel members follows a similar pattern allowing for some fluidity of practice. Generally, there is a period of social interaction and then warm-up exercises that may include meditation and/or mindful exercise prior to main exercise portion of the class. The major class time is dedicated to some form of Qigong/Tai chi exercise with periods of low activity or rest to accommodate varying levels of exercise tolerance, as needed, and integration of self-massage and meditation practice. Classes generally conclude with a short, interactive period that might include any combination of social support, discussion of stress reduction strategies and/or opportunity for questions and answers and discussion, or a quiet period of meditation. Qigong education might include application of energy cultivation and/or information about the latest research on Qigong in cancer care.  approved the Consensus recommendations for structure and delivery of Qigong exercise for Cancer care programming  did address current research to one degree or another in their classes. However, a caution was proffered that instructors be careful not to misrepresent research findings, so as to offer false hope. With regards to confidentiality, panel members confirmed the importance of maintaining confidentiality of personal and health information volunteered by participants. While preliminary, the information gained through this research has broad clinical implications. Foundational to recommendation generation is a belief that Qigong exercise in supportive cancer care programming has benefit and is complementary and integrative with, rather than alternative to, traditional medical management. All recommendations within the guidelines, serve to inform and guide rather than to regulate.Primary content recommendations include practice of mindful exercise (without reference to style or form), meditation, and self-massage. There is a wide variation among the Qigong instructors and programs represented in terms of use of Qigong styles and forms. Structure of programs varies depending on school of thought and philosophy  theory, emphasis on physical strength and prowess with martial art application, energy cultivation, or spiritual enlightenment with meditation or combinations therein). At least one instructor predominantly taught a traditional Tai chi form. Others reported teaching modified Tai chi forms combined with Qigong practice. While still others reported teaching only traditional or derivative Qigong forms. This variance was consistent with previous related research . SimilarMeditation has been recognized as an essential part of Qigong practice ,19,20. WNote: self-massage occurs naturally with exercise movements in the form of gentle stretching of the fascia, visceral massage, and gentle mechanical stimulation of articular surfaces within joints or may be applied as rubbing, tapping, body drumming or bone marrow washing, auricular massage, stroking of energy fields as in Reiki or therapeutic touch, even the vibration created from vocalization of healing sounds. Source: While recommendations on specific frequency and duration of practice were not delineated in this work, panel members agreed that availability of instructional aids to facilitate home practice should be recommended. Research on the importance of consistency of practice is not available for individuals with cancer. Though some insight may be gained from research on dose-response for other clinical populations. Chan et al. in an RCT of 150 women with chronic fatigue syndrome found that the number of Baduanjin Qigong lessons attended and the amount of Qigong self-practice were significantly associated with sleep, fatigue, anxiety, and depressive symptom improvement . Lynch ePanel members acknowledged the importance of instructor competence in Qigong exercise for cancer care. Participation in the research is considered tacit agreement that panel members invested in the belief that individuals with cancer are a vulnerable population and as such require instructor skills beyond entry level. These include competence within their craft, a general knowledge of cancer and associated adverse effects of cancer management, access to basic knowledge of current research in the area, as well as, sensitivities specific to the individual cancer journey. This knowledge expectation is beyond what might be expected of entry-level Qigong instructors where the student population is less vulnerable and health promotion is the primary goal of the Qigong practice. The guidelines for instructor competence, in terms of knowledge and skills for Qigong exercise in cancer care programming, can serve as a resource for among others, qigong instructors new to supportive cancer care, existing qigong instructors who value continuing professional development, educators who prepare this work force, and human resource professionals who staff programming.The current work has at least one major limitation related to validation. Validation is by consensus of expert opinion. Sampling method was one of convenience. By a priori design, the consensus panel sample does not include masters working in TCM settings. Voices of experts-in-the-field not included in the panel might have adjusted findings. Secondly, validity of recommendations is predicated on a belief that instructor competence directly influences outcome. Qigong in Cancer Care Guidelines: A Working Paper appended to this report . Prerequisite to this type of research is psychometric study, for example, development of standardized participant reported outcome tools to measure clinical outcome and a means to measure or certify level of instructor competence.The value of any applied clinical research lies in how well it improves practice. Awareness of the existence of this work will be raised by submission of informational postings through the National Qigong Association, the Qigong Institute, the Qigong Network, various instructor training workshops including a post conference workshop of the International Society for Integrative Oncology November 2017, Chicago, IL, USA, and invitation for social sharing among professionals in the field. It is hoped that instructors in existing programs will assess and modify their programs based on recommendations generated by the panel. For those just entering this clinical area of practice, regardless of the Qigong style of preference, and for administrators planning new programming consideration of these recommendations can aid and guide structure of respective programming.In conclusion, panel members agree that Qigong in cancer care be integrative with modern medical management. The environment should be nurturing, empowering and safe. The population served has special needs as compared to the general population, therefore the instructor should have a basic knowledge of cancer, its management and side effects of management to assure the safety of participants. Regardless of the style or form of Qigong taught in classes, the meditative and energy cultivation components of the exercises should be emphasized.


Disturbance regimes are changing worldwide, and the consequences for ecosystem function and resilience are largely unknown. Functional diversity (FD) provides a surrogate measure of ecosystem function by capturing the range, abundance and distribution of trait values in a community. Enhanced understanding of the responses of FD to measures of vegetation structure at landscape scales is needed to guide conservation management. To address this knowledge gap, we used a whole-of-landscape sampling approach to examine relationships between bird FD, vegetation diversity and time since fire. We surveyed birds and measured vegetation at 36 landscape sampling units in dry and wet forest in southeast Australia during 2010 and 2011. Four uncorrelated indices of bird FD  were derived from six bird traits, and we investigated responses of these indices and species richness to both vertical and horizontal vegetation diversity using linear mixed models. We also considered the extent to which the mean and diversity of time since fire were related to vegetation diversity. Results showed opposing responses of FD to vegetation diversity in dry and wet forest. In dry forest, where fire is frequent, species richness and two FD indices (richness and dispersion) were positively related to vertical vegetation diversity, consistent with theory relating to environmental variation and coexistence. However, in wet forest subject to infrequent fire, the same three response variables were negatively associated with vertical diversity. We suggest that competitive dominance by species results in lower FD as vegetation diversity increases in wet forest. The responses of functional evenness were opposite to those of species richness, functional richness and dispersion in both forest types, highlighting the value of examining multiple FD metrics at management-relevant scales. The mean and diversity of time since fire were uncorrelated with vegetation diversity in wet forest, but positively correlated with vegetation diversity in dry forest. We therefore suggest that protection of older vegetation is important, but controlled application of low-severity fire in dry forest may sustain ecosystem function by enhancing different elements of FD. Accelerating rates of environmental change present challenges to conservation practitioners worldwide ,2. The eIn theory, spatially variable environments offer more opportunities for resource partitioning and are thus expected to support greater FD . To dateIncreasingly, planned fire is used as a management tool to reduce the risk of large, intense wildfires and conserve biodiversity –25. EcolFire can directly cause mortality of individuals with particular traits  but our The direction and strength of relationships between FD and vegetation diversity are expected to vary with climate or productivity; responses of bird species diversity to forest management actions have been shown to differ along productivity gradients because the effects of vegetation structure are a function of available energy ,37. In hOur primary aim was to investigate relationships between FD and vegetation diversity in dry (low productivity) and wet (high productivity) forest. Our study area spanned a 70-year chronosequence in time since fire in the Otway Ranges, southeast Australia, where we used 36 landscape sampling units to test two hypotheses. First, we predicted a positive association between FD and vegetation diversity in dry forest where fire is frequent. Second, we anticipated a negative relationship between FD and vegetation diversity in wet forest subject to infrequent fire. In addition we examined relationships between vegetation diversity and time since fire to determine whether time since fire is a useful surrogate for vegetation diversity, and consequently FD. Collectively, results will help to elucidate the key environmental drivers of FD in southeast Australian forest systems, and guide ecological fire management in different forest types.The study area covered 59,000 ha of the Otway Ranges  in southeast Australia , where tTime-since-fire maps of the study area were derived from individual fire-history layers corresponding to every year since 1939. Large wildfires affected the study area in 1939 and 1983, and planned fire has been applied increasingly frequently since 2008. Planned burns are normally implemented such that 30–70% of vegetation remains unburnt . Severe Our sampling units were circular landscapes of 100-ha . During each survey year, sites were surveyed twice, once within four hours of sunrise, and once within three hours of sunset. Repeat surveys were undertaken on a different day, and observers were rotated among sites of different forest type, TSF and time of day to reduce the potential influence of observer bias. Surveys were conducted in good weather between September and December, which is the breeding season and is when most summer migrants arrive. Bird surveys were approved by the University of Melbourne School of Land and Environment Ethics Committee (Register Number 1011632.5), and field work was conducted under the National Parks Act (Research Permit Number 10005348) and Forests Act (Scientific Permit Number 10005514).Landscape-level presence-absence estimates were generated using data from within a 50-m radius of sites. Distance sampling has shown that although the mean probability of detection for species in the study area within 50 m is low , it does not vary significantly among recently-burnt and long-unburnt vegetation . To deriLandscape-level presence-absence data were used to derive estimates of landscape species richness and FD. To calculate FD, we focussed on six traits associated with resource acquisition and use, which are expected to influence relationships between species diversity and ecosystem function : body maWe derived indices of vertical and horizontal vegetation structural diversity from measures of four variables –53: loweWe combined measurements from the five sites in a landscape to quantify four indices of landscape-scale diversity, two based on vegetation structure, and two based on TSF. Both vertical and horizontal vegetation structural diversity were calculated using Shannon’s diversity index. Vertical diversity measured the extent to which vegetation was concentrated in one layer , or evenly distributed among layers . It was derived from the landscape means of the four vegetation structure variables, and was analogous to MacArthur and MacArthur’s  Foliage Additionally, we quantified the mean and diversity (Shannon’s diversity index) of TSF per landscape per year. TSF diversity distinguished landscapes that contained sites of five different TSF (low TSF diversity), to homogeneous landscapes of uniform TSF (high TSF diversity. The mean and diversity of TSF were positively correlated (r = 0.7) because homogeneous landscapes tended to be long-unburnt, so we did not use them as predictors in the same statistical models.Our analysis involved three stages; first we explored the responses of species richness and FD to vegetation diversity in wet and dry forest. Second, we examined relationships between the occurrence of individual traits and vegetation structure variables, and finally we considered the extent to which the mean and diversity of landscape TSF are related to vegetation diversity.2 as a measure of fit; marginal R2 was the variance explained by fixed effects, and conditional R2 was the variance explained by both fixed and random effects [In stage one, we used linear mixed models (LMM) to investigate responses of species richness and FD to vegetation diversity in wet and dry forest. The mixed-modelling framework accommodated variance associated with the nestedness of the design ; landsca effects .Stage two of our analysis involved identifying associations between the occurrence of individual traits and individual vegetation structure variables which are expected to underpin relationships between FD and vegetation diversity. Again, we quantified variables at the landscape scale (bird presence-absence and the mean cover of vegetation structure variables). We used a fourth-corner model that relates species traits to vegetation attributes by fitting a predictive model of species occurrence (L) as a function of matrices of vegetation structure variables (R) and species traits (Q) and their interaction ,60. The 2 to measure fit.During the final stage of analysis we considered the extent to which the mean and diversity of landscape TSF were related to vegetation diversity. We used the same statistical methods as in stage one; vertical and horizontal diversity were response variables and the mean and diversity of TSF were predictor variables in LMMs. Candidate model sets consisted of each predictor variable alone, and in additive and interactive combination with forest type, for a total of six candidate models. In all models, year was specified as an additive fixed effect, and landscape was specified as a random effect. We compared levels of support for models using information-theoretic model selection, and used marginal and conditional RResponses of species richness and FD to vegetation diversity differed in wet and dry forest, and in general, vertical diversity was a more important predictor than horizontal diversity . SpeciesThe fourth-corner analysis revealed associations between individual bird traits and vegetation structure variables . Some asBoth vertical and horizontal vegetation structural diversity were positively correlated with landscape TSF variables , but relDisturbance regimes are changing at unprecedented rates globally , and theFindings were consistent with our prediction of contrasting responses of FD to vegetation diversity in different forest types. Responses of species richness followed classical expectations in dry forest ,64, wherIn theory, positive responses of FD to vegetation diversity are driven by multiple associations between individual traits and individual elements of vegetation structure, and the fourth-corner analysis revealed many such interactions in dry forest. Among the stronger interactions were positive responses of fruit-eating and mixed-diet birds to canopy cover, and a negative response of bark-foragers to midstory cover; presumably these relationships were driven by food availability. We lack explanations for several of the stronger interactions, such as the positive response of arboreal granivores to lower understory cover; clearly, many factors are likely to interact with vegetation structure in influencing the occurrence of species’ functional traits.A patchwork of positive and negative responses of traits to vegetation structure was evident in both forest types; for example, while arboreal granivores responded positively to lower understory cover in dry forest, insect-eating and mixed-diet birds responded negatively. In wet forest, ground and understory foragers responded negatively to midstory cover, while builders of saucer-shaped nests responded positively. It is difficult to determine the relative importance of individual traits without detailed field observations over long periods , and theSome trait-vegetation interactions were common to both forest types, but associations were generally weaker and less numerous in wet forest. Differences in the number and strength of trait-vegetation interactions in wet and dry forest are congruent with studies that show vegetation diversity is more important when productivity is lower and disturbance more frequent . FurtherThe response of FEve to horizontal diversity presents a major exception to general trends; responses were opposite to those of species richness, FRic and FDis. In wet forest, while FRic and FDis decrease with increasing vegetation diversity, the distribution of species in functional space becomes more even , and theVertical diversity was the best predictor of four out of our five bird response variables, in accordance with many studies that show Foliage Height Diversity  is a principal driver of bird species diversity ,71,72. RForests support a high proportion of global biodiversity , but the


Understanding and addressing treatment abandonment (TxA) is crucial for bridging the pediatric cancer survival gap between high-income (HIC) and low-and middle-income countries (LMC). In childhood cancer, TxA is defined as failure to start or complete curative cancer therapy and known to be a complex phenomenon. With rising interest on causes and consequences of TxA in LMC, this study aimed to establish the lay-of-the-land regarding determinants of TxA globally, perform and promote comparative research, and raise awareness on this subject.Physicians , nurses, social workers, and psychologists involved in care of children with cancer were approached through an online survey February-May 2012. Queries addressed social, economic, and treatment-related determinants of TxA. Free-text comments were collected. Descriptive and qualitative analyses were performed. Appraisal of overall frequency, burden, and predictors of TxA has been reported separately.581 responses from 101 countries were obtained . Most respondents were physicians (86%), practicing pediatric hematology/oncology (86%) for >10 years (54%). Providers from LMC considered social/economic factors , as most influential in increasing risk of TxA. Treatment-related considerations such as preference for complementary and alternative medicine and concerns about treatment adverse effects and toxicity, were perceived to play an important role in both LMC and HIC. Perceived prognosis seemed to mediate the role of other determinants such as diagnosis and treatment phase on TxA risk. For example, high-risk of TxA was most frequently reported when prognosis clearly worsened , or conversely when the patient appeared improved , as well as before aggressive/mutilating surgery. Provider responses allowed development of an expanded conceptual model of determinants of TxA; one which illustrates established and emerging individual, family, center, and context specific factors to be considered in order to tackle this problem. Emerging factors included vulnerability, family dynamics, perceptions, center capacity, public awareness, and governmental healthcare financing, among others.TxA is a complex and multifactorial phenomenon. With increased recognition of the role of TxA on global pediatric cancer outcomes, factors beyond social/economic status and beliefs have emerged. Our results provide insights regarding the role of established determinants of TxA in different geographical and economic contexts, allow probing of key determinants by deliberating their mechanisms, and allow building an expanded conceptual model of established and emerging determinants TxA. Treatment abandonment (TxA) is a leading cause of treatment failure for children with cancer in low- and middle-income countries (LMC).–5 TxA enThis study aimed to establish the lay-of-the-land regarding determinants of TxA globally, perform and promote comparative research, and raise awareness on this subject by capturing data directly from healthcare providers taking care of children with cancer in a variety of regional and economic settings. This study complements efforts in the global pediatric oncology community to assess the global burden of TxA, evaluatewww.cure4kids.org) offered the broadest representation of pediatric hematology and oncology clinicians globally. Cure4Kids is a free online education and collaboration resource with diverse international membership dedicated to supporting the care of children with cancer and other catastrophic diseases worldwide.[An internet-based survey was conducted on a convenience sample in order to obtain up-to-date information from providers and centers globally. At the time this study was conducted, Cure4Kids , nurses, social workers, and psychologists involved in the care of children with cancer were approached. Email addresses were obtained from the Cure4Kids member directory after ethics approval. Authors never had direct access to the master distribution list. Eligibility was confirmed through two screening questions. Students, data managers, parents and patients were excluded.Subjects received an individualized email-specific link, four reminders, and details regarding research activity and purpose. The survey remained open from February 10 to May 10 of 2012. Patient-level data was not collected or analyzed.Survey data was analyzed using Excel and SAS 9.3. Countries were classified according to the World Bank Atlas Method by reporThis study was approved by the Institutional Review Board (IRB) at St. Jude Children’s Research Hospital and Dana-Farber Cancer Institute.The survey was sent to 3,242 email addresses. It obtained an overall contact rate of 26% and a cooperation rate of 70% for the sections of interest for this study (based on definitions established by the American Association for Public Opinion Research). In parDespite drawing from a convenience sample, the survey obtained responses from 101 countries, including all continents and country-income groups (Subjects were predominantly physicians (86%); pediatric hematologists-oncologists in particular (Most respondents (65%) worked in medium to large centers and only 3% of subjects reported working in private clinics . The categories “always/almost always” and “often” were aggregated to reflect high-likelihood of TxA. A “not applicable” option was available and it was removed from the denominator, resulting in a variable effective response rate by diagnosis; while retaining comparability across diagnoses. As seen in high-likelihood was reported most frequently for bone sarcomas (20% of providers) and least frequently for Hodgkin disease and Wilms tumor (4%), although several diagnoses shared a similar range (10–13%); acute myeloid leukemia, retinoblastoma, acute lymphoblastic leukemia, brain tumors, and soft tissue sarcomas. Each diagnosis frequency’s ranking and range varied depending on the country’s income category .Factors perceived to play an important role in both LMC and HIC: preference for complementary and alternative medicine (CAM) and concern for adverse effects and toxicity.Factors perceived to play a moderate role in HIC, but comparatively lower in LMC: strongly held faith or religious beliefs and older age/adolescent.Factors perceived to play a moderate role in both LMC and HIC: belief in incurability of cancer, insufficient communication, and painful diagnostic or therapeutic procedures.Factors perceived to play minor role, but comparatively higher in LMC than HIC: malnourishment, HIV status, younger age, and female gender.The same 15 factors were analyzed by geographical group  looking likelihood of TxA in their setting. The summary from 194 interpretable responses provided by 104 subjects is presented in contextual factors such as the issue of healthcare financing, b) center and care delivery-related factors such as the negative impact of poor infrastructure and limited human resources at the center, c) family factors such as competing family crises and problematic family dynamics, and d) patient factors related to vulnerability or treatment, such as immigration status and need for/fear of aggressive surgery, respectively. Themes not previously reported included the protective impact of personal character and the negative impact of belonging to vulnerable populations, such as discriminated, native/indigenous, or immigrant populations. Immigration status was identified as a factor specifically important in UMIC and HIC, where other factors are presumably lessened.In an effort to identify additional and/or emerging factors, subjects were asked to provide comments and to suggest factors that influenced the contextual factors such as lack of healthcare coverage for immigrant populations and the negative impact of mis-information in the media; care delivery factors such as informed consent for therapy when language barriers exist, and the issue of respecting adolescent autonomy in medical decision-making ; and family and patient-related factors, such as parental worries regarding unexpected side effects, the impact of strong religious beliefs or preference for CAM, and the issue of non-adherence with oral medications.Although comments from providers from HIC were less frequent, they expressed particular concerns regarding Treatment abandonment (TxA) is complex and multifactorial, but understanding and addressing it is vital to bridge the survival gap between HIC and LMC. This is the first study to collect data directly from healthcare providers taking care of children with cancer in a wide variety of regional and economic settings globally. Our results provide valuable insights regarding the role of recognized determinants of TxA such as diagnosis, treatment phase, prognosis, social/economic factors, and beliefs in different geographical and economic contexts. Results also allow probing key established determinants by deliberating their mechanisms and building an expanded conceptual model that takes into account established and emerging patient, family, center, and context factors that influence the risk of TxA .Our results show variability in the likelihood of TxA by diagnosis (high for bone sarcomas and low for Hodgkin lymphoma and Wilms tumor), with the range of this TxA likelihood and the ranking of specific diagnoses varying by socioeconomic context; a finding consistent with other studies documenting higher rate of TxA for specific diagnoses ., 14–16 HWe believe documenting this differential in the likelihood of TxA by diagnosis offers two take-home messages. First, centers should track TxA by disease (and not assume that the frequency of TxA observed for one disease applies to other diseases) in order to identify patient populations at higher risk of TxA or for whom the current strategies to prevent TxA are not working. Second, as interventions and priorities are established, centers should keep in mind the potential untapped opportunities to increase survival outcomes through TxA prevention in children with curable cancer.As previously mentioned, we hypothesized that social/economic context, aggressiveness of the treatment strategy, and prognosis could serve as mediators between diagnosis and TxA. Providers’ comments supported our hypothesis. For example, the frequency rankings varied by country income group, the need for aggressive and/or mutilating surgery was repeatedly suggested to play a direct role, and the highlighting of specific diagnoses often reflected a comment on prognosis (for example “infant with CNS tumor” or “metastatic sarcoma”). The analysis also revealed the center’s capacity  and perceived  prognosis as additional mediators. A recent assessment of pediatric oncology centers in Myanmar showed higher TxA for retinoblastoma compared to other oncologic diseases and supported the idea that lack of specialists, radiation services, and supportive care contribute to TxA for this diagnosis in their setting. PerceiveThe role of treatment phase as a determinant of TxA was considered of interest because most studies show TxA to occur early–in the first 3 months of therapy., 27–31 TBased on published literature, several other determinants of TxA were assessed . Providers from LMC placed social/economic factors at the top. This finding is consistent with single-institution retrospective studies showing economic constraints , low parental education (or literacy), and long travel time to be associated with increased risk of TxA, 36–42 aProviders from HIC and LMC concurred on preference for CAM and concerns regarding treatment toxicity as important; in aggregate, these ranked highest in HIC and second highest in LMC. A possible increase in refusal arising from the appeal of CAM in HIC has been postulated, supporteOther factors ranked as contributing to TxA included belief in the incurability of cancer, insufficient communication, strongly held faith or religious beliefs, and painful procedures; determinants supported by several single institution studies., 40, 42 With increased recognition of the role of TxA on global pediatric cancer outcomes, factors Vulnerability–Immigration status was brought up by providers from HIC, who described poor access to care when these children do not qualify for national health care coverage. Long-hospital stay and treatment course were also endorsed .Family dynamics–The role of family dynamics and the connection between families and their communities were of particular interest. Studies show parents are motivated to cure their child with cancer, even in very low resource settings., 50 HowePerceptions–Public perception of cancer is likely very different on HIC and LMC. In HIC, investment by private citizens in fundraising and awareness campaigns for cancer (and childhood cancer in particular) has been strong for decades, allowing cancer to inspire individual resilience and social thriving. In LMC, where the burden of cancer mortality is high and public awareness campaigns are relatively young, a diagnosis of childhood cancer may be poorly accepted or understood. The role of beliefs as a determinant of TxA presented by providers went beyond religiosity or disbelief in curability of cancer. Providers highlighted disbelief in the center’s capacity and past family experiences with cancer as additional factors influencing the risk of TxA.Center’s capacity: This was highlighted as a determinant of TxA in terms of human resources, infrastructure, supportive care, and internal health delivery systems. Most studies looking at determinants of TxA focus on the family. However, the role providers and centers play in swaying this phenomenon are emerging, 40, 52 Context: The issue of healthcare financing for catastrophic illnesses and the need to protect families from financial suicide is one that burdens policy makers in HIC and LMC. RegardinIn conclusion, TxA is a complex and multifactorial phenomenon. Our results provide valuable insights regarding the role of recognized determinants of TxA in different geographical and economic contexts. Results also allow probing of key determinants by deliberating their mechanisms and building an expanded conceptual model that takes into account patient, family, center, and context factors that influence the risk of TxA.Regarding the limitations of our study, by using an online English-language platform and drawing from a convenience sample, we likely lowered the chances of receiving information from LIC and possibly selected for more motivated individuals. However, when this study was conducted, the Cure4Kids online membership offered the largest and most diverse cohort of pediatric hematology and oncology providers available to conduct this study. Although not fully representative, the sample achieved was sufficient to meet the exploratory aims of the study. Furthermore, contact and cooperation rates achieved were comparable to other global surveys.–66 We alS1 Table(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S1 FigDark blue, HIC = high-income countries; light blue, UMIC = upper-middle-income countries; light green, LMIC = lower-middle-income countries; dark green, LIC = low-income countries; HL = Hodgkin Lymphoma, NHL = Non-Hodgkin Lymphoma; WT = Wilms tumor; RB = Retinoblastoma; STS = Soft tissue sarcoma; ALL = Acute lymphoblastic leukemia; GLIOMA = Brain glioma; AML = Acute myeloid leukemia; BS = Bone sarcoma; and MB = Medulloblastoma.(PDF)Click here for additional data file.S2 FigThe category “increases likelihood of TxA” entailed report of “increases” or “strongly increases” likelihood of TxA. HIC, high-income countries; LMC, low- and middle-income countries; TxA, treatment abandonment; CAM, complementary and alternative medicine.(PDF)Click here for additional data file.S1 TextThe data presented in this manuscript pertains primarily to questions 1–12, 14–20, and 32 of the survey tool used for data collection. Results for other sections have already been (see text) or will be summarized in additional manuscripts.(PDF)Click here for additional data file.


Reversing conditions characterized by intellectual disability or dementia is one major challenge in basic and applied Neuroscience. This varied group of pathologies is highly heterogeneous and comprises, among others, neurodevelopmental disorders such as autism, Rett syndrome, and Down syndrome, and age-dependent neurodegenerative diseases such as Alzheimer’s disease (AD). Despite the heterogeneous etiology, recent research has underscored common cellular and molecular mechanisms underlying key neuropathological signs associated with these disorders, with emerging hub roles for GABAergic overinhibition, altered mGluR signaling, alterations in key neurotrophic factors, and dysfunctions in the metabolism of β-amyloid protein. The increased knowledge of molecular details has greatly expanded the attempts aimed at a pharmacological correction, with a growing number of studies reporting a marked phenotypic rescue in various transgenic mouse models of these disorders.One paradigmatic case is that of Down syndrome (DS), a condition due to the presence of an extra copy of the human chromosome 21 and representing the most common genetic cause of intellectual disability. People with DS exhibit a complex phenotype characterized by a wide range of functional dysfunctions, encompassing attention and sensory deficits and moderate to severe mental retardation [While awaiting for the good cocktail of pharma, mother Nature can go to Nurture’s school to get some help, or hints, or a combination of the two. In the last decades environmental enrichment (EE), a combination of sensory, motor and cognitive stimulation, has emerged as a valuable tool capable to stimulate cerebral plasticity both during the development and in the adulthood, with a totally non-invasive approach that renders this paradigm particularly interesting in terms of application to humans. EE exerts powerful effects on neural connectivity, enhancing hippocampal synaptic plasticity and learning and memory abilities, and positively interacting with various factors involved in neural plasticity, including NMDA receptors, inhibitory circuitry, intracellular kinases, neuromodulators, hippocampal neurogenesis, transcriptional and epigenetic factors, and neurotrophins . FocusinStrikingly, the beneficial effects of EE are not restricted to early life stages. Long-term exposure to EE prevents, in the hippocampus of aged Ts65Dn mice, the age-dependent increase of low molecular weight Aβ oligomer isoforms, the most dangerous molecular species triggering synapse failure and memory impairment in AD-like dementia .Normalization of development, reversion of adult dysfunctions, prevention of AD-like neuropathology in elderly subjects: these remarkable effects should not be held as a miracle, as they rely on the EE ability to impact at several molecular substrate levels in the brain, including stimulation of maturational processes by enhancing the activation of growth factors, reopening of plasticity windows through reduced intracortical inhibition and promoting plastic structural and functional changes through neurotrophin increments, which could in turn increase the expression of genes specifically involved in brain plasticity.These studies have profound consequences for humans. The development of intervention protocols aimed at ensuring proper levels of environmental stimulation and at maintaining a healthy and active lifestyle has been effectively encouraged by basic research on EE. A recent study in humans showed that an early multisensory intervention, based on infant body massage and directly inspired by research on maternal stimulation in rodents, promotes a significantly higher visual acuity in DS children at 6 months of age, leading to an accelerated development which persists up to at least 12 months . Strong Future treatments in this field should combine the administration of new pharmacological therapeutics with an endogenous pharmacotherapy based on the intrinsic capability of environmental stimulation to enhance the spontaneous reparative potential held by the brain.


Healthcare systems around the world have been responding to the demand for better integrated models of service delivery. However, there is a need for further clarity regarding the effects of these new models of integration, and exploration regarding whether models introduced in other care systems may achieve similar outcomes in a UK national health service context.The study aimed to carry out a systematic review of the effects of integration or co-ordination between healthcare services, or between health and social care on service delivery outcomes including effectiveness, efficiency and quality of care. Electronic databases including MEDLINE; Embase; PsycINFO; CINAHL; Science and Social Science Citation Indices; and the Cochrane Library were searched for relevant literature published between 2006 to March 2017. Online sources were searched for UK grey literature, and citation searching, and manual reference list screening were also carried out. Quantitative primary studies and systematic reviews, reporting actual or perceived effects on service delivery following the introduction of models of integration or co-ordination, in healthcare or health and social care settings in developed countries were eligible for inclusion. Strength of evidence for each outcome reported was analysed and synthesised using a four point comparative rating system of stronger, weaker, inconsistent or limited evidence.One hundred sixty seven studies were eligible for inclusion. Analysis indicated evidence of perceived improved quality of care, evidence of increased patient satisfaction, and evidence of improved access to care. Evidence was rated as either inconsistent or limited regarding all other outcomes reported, including system-wide impacts on primary care, secondary care, and health care costs. There were limited differences between outcomes reported by UK and international studies, and overall the literature had a limited consideration of effects on service users.Models of integrated care may enhance patient satisfaction, increase perceived quality of care, and enable access to services, although the evidence for other outcomes including service costs remains unclear. Indications of improved access may have important implications for services struggling to cope with increasing demand.42016037725.Prospero registration number: The online version of this article (10.1186/s12913-018-3161-3) contains supplementary material, which is available to authorized users. It has been argued that growing financial and service pressures in the UK National Health Service (NHS) cannot be tackled without transforming how health and social care are delivered. The NHS Five Year Forward View Plan published in 2014 . The driIn the desire to accelerate the pace of integration, initiatives from around the world have been recommended as useful models from which the NHS can learn. However, some authors have emphasised that it is imperative to consider contextual differences before implementing the same models in different services and location . While iIn a landscape of changing service delivery and uncertainty regarding effectiveness of new models, we undertook a systematic review to examine the literature on outcomes of integrated care. Given the potential for learning from integrated models across the world, we aimed in particular to compare evidence from the UK and international literature, to explore where similarities and difference in effects have been reported. This paper focuses on data relating to the effects of models of integrated care on actual and perceived service delivery, including the efficiency, effectiveness and quality of care. Other findings from this study including factors influencing implementation and outcomes are reported elsewhere .Highly complex system-wide interventions such as models of integrated care provide considerable challenges for systematic review methods . SystemaThe study protocol was registered with the PROSPERO database (number 42016037725) and was made available on the National Institute for Health Research website  and NHS England (https://www.england.nhs.uk). In May 2017 we conducted a citation search to identify any literature published subsequent to the formal bibliographic searches.The information specialist on the team carried out systematic searches of health, medical and social care databases in September 2016. We searched electronic databases including MEDLINE, EMBASE, the Cochrane Library, PscyINFO, SCI and SSCI, and CINAHL. Further details of the search strategy are available in the Additional file We sought studies of systematic review, randomised and non-randomised controlled trial, prospective or retrospective cohort (with or without comparators), before and after/longitudinal design, and cross-sectional studies.We included studies reporting any outcome relating to the delivery of services  and/or the effect on patients and staff delivering services.Studies were required to have been carried out in a developed country (a member of the Organisation for Economic Collaboration and Development) and to have been published since 2006 in English, or have an English abstract. We searched from this year as a previous review is available which included studies published up to 2006 .We defined “models of integrated care” as changes to health or both health and health-related service delivery which aim to increase integration and/or coordination.Studies were excluded if they reported only clinical, rather than service delivery outcomes, or if integrated services did not include healthcare. We included grey literature from the UK in the form of reports, but conference abstracts and theses were excluded.Retrieved citations were uploaded to an EndNote database, and title and abstracts (where available) of papers were screened by three reviewers against the inclusion/exclusion criteria. Any queries regarding inclusion were discussed by the full team at regular (fortnightly) team meetings. After independent screening and discussion of the first 5% of the database to establish agreement, further screening was carried out by a single reviewer, with checking of a 10% sample by other team members.Articles which met the inclusion criteria were read in full and data extracted by the team of three reviewers. Data extractions were second-checked by a different member of the team. Papers excluded and the reason for exclusion was recorded  . Where sOur protocol allowed for meta-analysis if heterogeneity permitted. However, the wide variety of models of integrated care, and multiple and complex elements contained therein, together with the heterogeneity of outcomes measured, contra-indicated the use of summary statistics. Instead, we report where there is greater or lesser strength (or certainty) in the evidence for each outcome reported .It is important that any assessment of strength of evidence considers not only quality and volume of studies, but also considers consistency . Our evaEach outcome reported in a study was recorded as either “increase”, “reduction” or “no significant difference .” We used these terms, as for some outcomes the judgement of being positive or negative depends on ones point of view. For example an increase in service usage may be positive for patients or the service, but may also be negative in terms of costs or detrimental effect on other services. Following rating of the outcomes in each individual study, we then applied an overall rating to the evidence across all studies which reported the same outcome. The rating scale was as follows: “stronger evidence” represented generally consistent findings in multiple studies with a comparator group design, or three or more systematic reviews; “weaker evidence” represented generally consistent findings in one study with a comparator group design and several non-comparator studies, or two systematic reviews, or multiple non-comparator studies; “very limited evidence” represented an outcome reported by a single study; and finally, “inconsistent evidence” represented an outcome where fewer than 75% of studies agreed on the direction of effect.We separately rated evidence from the UK studies, evidence from systematic reviews, evidence from the international comparator studies, and evidence from international non-comparator studies, and then provided an overall rating of effect across the study types.Following screening of 13,323 unique citations, 167 documents representing 153 unique studies were eligible for inclusion. See Fig. The list of studies excluded at the full paper selection stage and reasons for their exclusion is available as an Additional file Of the 167 included documents, 54 reported studies carried out in the UK –73, and We observed little overlap between primary studies and reviews, with time lags in publication of the systematic reviews meaning that the majority of their primary studies preceded our inclusion date of 2006. Figure While there were large numbers of studies from both primary/community services, and acute care, the larger group was initiatives implemented outside hospital settings. Thirty five studies were carried out in primary care/community contexts, 24 studies were carried out solely in hospital settings, and two were carried out in nursing homes. Nineteen studies specifically described both health and social care services being included in the integration, although reporting of specific details of partner organisations/services was often limited. Authors did not make links between the context and outcomes of initiatives, apart from reported issues regarding staff training and retention in social care . and theOf the included 54 UK articles, 16 reported findings from studies using higher quality comparator designs , 71, 72.The international comparative design studies rated slightly better in terms of randomisation with 19 (reported in 26 papers) having random allocation , 164, alp values) to evaluate change over time.The UK before and after/longitudinal studies demonstrated similar issues regarding blinding, with only one study clearly reporting that outcome assessors were blinded . GeneralThe majority of the included models of integrated care were complex and multi-element interventions. The elements contained within them could be divided into four main categories: first, those with a focus on improving patient care directly; secondly, those that focused on making changes to organisations and systems; thirdly, those that focused on changing staff employment or working practices; and finally, those that addressed financial or governance aspects of integration. Many models incorporated multiple elements, and it was often challenging to elucidate the form and components due to limited reporting. The greatest number of elements we could identify in a single intervention was nine, which compared with other integrated care initiatives containing a single element. Typically models contained four to six elements. Case manager/case co-ordinator initiatives were more common in the international literature, whereas integrated care pathways/plans were more often a feature of models in the UK. Figure We identified an extensive range of outcomes from the literature. We grouped these into three main areas: those relating to usage of health care resources; those relating to the quality of care received by patients; and outcomes for staff working experience. We adopted the four-item rating scale described in the Methods section to evaluate the quantity and consistency of available evidence for each outcome. We provide the rating for studies from the UK, international systematic reviews, international primary studies and finally an overall rating of available evidence. Where reports of outcomes were duplicated in multiple papers from the same study we identify only one instance, to avoid over-representation of these data. Additional file The evidence was rated as stronger for three outcomes: that integrated care leads to an increase in patient satisfaction; that integrated care leads to increased perceived quality of care ; and that integrated care can lead to increased/improved patient access. UK studies indicated evidence of a reduction in waiting times and out-patient appointments, although the international literature as a whole was more inconclusive.Nine of 11 UK studies evaluating differing types of interventions across a range of conditions and services reported increased levels of patient satisfaction , 61, 69.Four UK intervention studies reported staff perceptions of increased quality of care following service redesign, case management or integrated pathway interventions in hospital or primary care for older adults, general caseloads or patients with C-difficile infection , 58, 69.Five included (non-comparator) UK intervention studies reported that access to services in the community and/or specialists/intermediate care had increased , 72, 73.In regard to similarities and differences between studies carried out in the UK and in other countries, we found three areas of variance in rating between UK evidence and the evidence overall. Five UK studies offered evidence of a reduction in waiting times , 61, 71.Evidence regarding the following outcomes was rated as inconsistent: number of clinician contacts ; number of GP appointments (two UK studies reported a reduction and another UK study no difference); length of stay ; unscheduled admissions ; number of admissions  although considered alone the systematic reviews provided stronger evidence of a reduction; re-admissions ; attendance at accident and emergency ; quality of care standards (two studies reported an increase and one no difference); and staff work experience .The rating of very limited evidence (insufficient studies) was assigned to the following outcomes: prescribing rates; access to resources; time spent in accident and emergency department; the number of incidents/complaints; and identification of unmet need.We also examined evidence relating to wider impacts across the whole of a healthcare system. The evidence was inconsistent regarding the impact on cost of provision ; community care activity ; secondary care activity ; and overall healthcare utilisation (two systematic reviews found the evidence was unclear).We explored the potential for sub-group differences between different types of patients. Figure We examined the data regarding outcomes and impacts for studies in the two largest sub-groups of patients - older adults, and populations described as having complex needs. We then compared this to the strength of evidence ratings assigned to the included studies as a whole. The effect of integrated care initiatives in older adult populations echoed the strength rating for all studies, with reports of increased access and patient satisfaction, and inconsistency in regard to admissions, emergency admissions, length of stay, patient contacts/service usage, and costs.In contrast to the wider evidence base however, the evidence on patients described as having “complex needs”, suggested a stronger indication of positive outcomes in terms of reduced admissions and emergency department use, and weaker strength of evidence regarding reduced length of stay. The studies all utilised non-comparator designs however, so this indication needs to be treated with caution. We also looked for any patterns in regard to the type of initiatives that appeared to lead to more positive outcomes, with little clarity in signal beyond suggesting that integrated pathways as “stand alone” interventions may have a limited effect.Models of integrated care encompass diverse initiatives that aim to improve integration of care across healthcare and between health and social care services. We identified diverse and frequently contradictory outcomes for models of integrated care reported in the included literature. Three outcomes appeared to offer stronger evidence of effect: firstly, that integrated care leads to increased patient satisfaction; secondly, that integration increases perceived quality of care; and thirdly, that integrated care increases patient access to services. UK-only evidence indicated that patient waiting time and outpatient appointments may be reduced, and patient wishes at end of life are met more often . The system-wide impact on community and hospital-based services was unclear, with reports of both increased and decreased use of community services, although we identified no evidence to suggest that models of integrated care increase use of secondary care. Neither was there clear evidence regarding whether models of integrated care are cost neutral, increase or reduce costs. The review identified numerous changes to delivery of services which are subsumed within the label of models of integrated care. As highly complex interventions, these models challenge linkage of particular elements of initiatives to effects, with a lack of clarity on which key elements are causally associated with positive outcomes.We highlight the challenges inherent when defining models of integrated care, given the lack of agreed definition and clear boundaries to the term. This limitation may have resulted relevant work being excluded from this review. We found it particularly challenging to distinguish between new models of care that are integrated/co-ordinated from those that are not during the screening and selection process. “Integration” could be used in a variety of ways, including to describe interventions which related to enhanced care or quality assurance but did not include staff working in new ways. Although our search terms enabled relevant citations to be retrieved, we recognise that indexing may be imperfect, and we may have not identified all studies of relevance. We also acknowledge a potential issue of publication bias, with studies reporting less positive outcomes potentially under-represented in the review. We highlight the paucity of literature reporting objective quality of care outcomes, with our findings regarding the effect on quality based on staff or patient perceptions.One particular limitation relates to the lack of statistical summary of effectiveness  although we would argue that not only did the heterogeneity of interventions and outcomes preclude this type of analysis, but also, in exploring the complexity of the area a strength of evidence approach was beneficial. Included studies highlighted the challenges in identifying causal relationships between models of integrated care, and service delivery impacts , 120–122Evaluating outcomes and impacts from models of integrated care presents challenges in determining what a “good” outcome may be. In terms of financial outcomes, the effects of integrated care may be perceived differently by different stakeholders, offering contradictory incentives for achieving change. At an organisational level for example reduced activity in one sector may mean financial losses. There are also known to be considerable challenges in transferring money or resources between organisations in response to changed levels of activity. Another tension exists between cost-saving and provision of improved quality of care. Some studies reported that increasing quality of care for patients may come at increased cost for services already facing financial pressure.The potentially positive outcome of increasing ease of access for patients, also offers contradictory effects. Improved access may be perceived positively by patients, and enable serious conditions to be identified and treated earlier; but also may incur a detrimental effect on costs and capacity. Recognition is growing that rather than new models of integration within services, reform at scale is required, with reconfiguration at a whole systems level including in the UK new forms of commissioning and contracting (the way that NHS organisations assess the needs of an area and then draw up contracts with suitable providers) . The litThe implementation of highly complex whole-system change interventions such as new forms of integration is known to be challenging , and difThis review adds to the growing evidence that integrated care initiatives rarely lead to unequivocally positive effects, although the calls for integrated care have never been stronger. The potential for integrated services to increase patient contacts, is a particular concern in already over-stretched services. New models of care may be best targeted to particular patient groups (such as those with complex needs) rather than being seen as a panacea for all.We identified surprisingly little evidence regarding the impact of integrated care models on patient experiences of services, beyond measures of reported patient satisfaction. There seems a need for further attention to how reconfiguration impacts on patients and carers, including whether service users perceive any change, or have greater knowledge of or involvement in services.Additional file 1:Appendix S1. Study protocol. Appendix S2. Completed PRISMA checklist. Appendix S3. Search strategy. Appendix S4. Studies excluded at full paper screening. Appendix S5. Completed quality appraisals. (DOCX 197 kb)Additional file 2:Table S1. Summary of studies and effect for each outcome (DOCX 335 kb)