An assessment tool is needed to measure the clinical severity of nursing home residents to improve the prediction of outcomes and provide guidance in treatment planning.This study aims to describe the development of the Nursing Home Severity Index, a clinical severity measure targeted for nursing home residents with the potential to be individually tailored to different outcomes, such as pressure injury.A retrospective nonexperimental design was used to develop and validate the Nursing Home Severity Index using secondary data from 9 nursing homes participating in the 12-month preintervention period of the Turn Everyone and Move for Ulcer Prevention (TEAM-UP) pragmatic clinical trial. Expert opinion and clinical literature were used to identify indicators, which were grouped into severity dimensions. Index performance and validation to predict risk of pressure injury were accomplished using secondary data from nursing home electronic health records, Minimum Data Sets, and Risk Management Systems. Logistic regression models including a resident’s Worst-Braden score with/without severity dimensions generated propensity scores. Goodness of fit for overall models was assessed using C statistic; the significance of improvement of fit after adding severity components to the model was determined using the likelihood ratio chi-square test. The significance of each component was assessed with odds ratios. Validation based on randomly selected 65% training and 35% validation data sets was used to confirm the reliability of the severity measure. Finally, the discriminating ability of models was evaluated using propensity stratification to evaluate which model best discriminated between residents with/without pressure injury.P<.001) when adding four severity dimensions to Worst-Braden scores. Significantly higher odds of developing pressure injuries were associated with increasing dimension scores. The use of the three highest propensity deciles predicting the greatest risk of pressure injury improved predictive accuracy by detecting 21 more residents who developed pressure injury  when both severity dimensions and Worst-Braden score were included in prediction modeling.Data from 1015 residents without pressure injuries on admission were used for the Nursing Home Severity Index–Pressure Injury and included laboratory, weights/vitals/pain, underweight, and locomotion severity dimensions. Logistic regression C statistic measuring predictive accuracy increased by 19.3% (from 0.627 to 0.748; The clinical Nursing Home Severity Index–Pressure Injury was successfully developed and tested using the outcome of pressure injury. Overall predictive capacity was enhanced when using severity dimensions in combination with Worst-Braden scores. This index has the potential to significantly impact the quality of care decisions aimed at improving individual pressure injury prevention plans.ClinicalTrials.gov NCT02996331; http://clinicaltrials.gov/ct2/show/NCT02996331 The aging of the population has resulted in over 1.3 million residents living in nursing home facilities in the United States . NursingClinical severity, the extent of physiologic decompensation, reflects the overall complexity of a resident’s health status. The severity of illness measures initially were developed in the 1980s using supervised techniques that predict a specific target value, applying statistical methods with historical data. These measures helped to explain why patient mortality, cost, or length of stay differed among hospitals. Their ability to accurately predict a variety of outcomes, however, was limited given that patient attributes were in part defined by specified treatments and created using regression analyses to predict one outcome -9.The Comprehensive Severity Index (CSI) ,11, whicThe development of a clinical severity measure targeted for nursing home residents requires the construction of a new measure with the potential to be individually tailored to different outcomes, such as a PrI. The CSI and other existing clinical severity measures are not appropriate for use with nursing home residents who have large variations in their length of stay, the time windows for data collection, and documentation frequency. This paper reports on the creation of a new clinical severity measure, Nursing Home Severity Index (NHSI), tailored for PrI risk prediction for nursing home residents, and validation using propensity modeling to predict PrI development and explore the measure’s predictive accuracy beyond the Braden score.Development of the NHSI and the selected attributes associated with PrI risk (NHSI-PrI) required initial variable selection, scoring, validation, and propensity modeling to account for independent and confounding variables that affect PrI development and exploration of the measure’s predictive accuracy and validity. A retrospective nonexperimental design was used to examine a broad range of resident attributes to develop the NHSI-PrI. Current study data were based on a 12-month longitudinal data set from each study nursing home to account for seasonal differences.Residents from 9 skilled nursing homes participating in a 12-month preintervention period (hereafter study period) of the Turn Everyone And Move for Ulcer Prevention (TEAM-UP) embedded pragmatic cluster randomized trial  ,19 were Duke University Institutional Review Board (Duke IRB-Pro00069413) approved the parent project with a waiver of informed consent for nursing home residents.The NHSI-PrI is a measure of clinical severity for nursing home residents focused on the outcome of PrI risk and development. The first step in creating the NHSI-PrI was selecting the resident attributes to include those that are relevant to a nursing home population. The NHSI-PrI differs from prior clinical severity measures for acute, ambulatory, or rehabilitation care as it needs to account for greater variability in the length of time residents live in nursing homes and lower frequency of assessments, laboratory, and radiological tests. Skilled care in nursing homes often involves extended stays and uses different frequencies of diagnostics and treatments  from those of other care environments. Acute illness is less common, so laboratory tests are drawn infrequently and often only when there is an acute event. Assessments are made periodically such as at initial admission, quarterly, annually, and on condition change. Residents may need short- or long-term skilled care while recovering from an illness or surgery. Skilled care is characterized by wound and postsurgical care; injected medications; intravenous therapy; physical, occupational, and speech therapy; and regular monitoring of vital signs or disease-specific parameters such as blood glucose levels. Thus, a refined approach to severity measurement was needed to develop a meaningful profile of nursing home residents’ clinical severity.International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes used for residents within the study period were extracted and similar diagnoses combined . For each diagnosis aggregate, a comprehensive set of relevant clinical severity indicators of resident attributes was derived from a combination of CSI criteria sets and other sources including Minimum Data Set (MDS) elements, nursing point of care documentation, and Risk Management System data elements: demographics  and clinical attributes . The inclusion of several of the NHSI severity indicators derived from the federally mandated assessment documentation for Medicare and Medicaid–certified long-term care facilities (MDS) used standardized clinical measures of functional capabilities and health needs specific to nursing home residents.The second step in the NHSI-PrI development examined the associations and correlations of the severity indicators. Multiple indicators considered as alternative ways to describe the same resident attribute were combined into a single equivalence set .The third step developed algorithms to score the NHSI-PrI. A matrix was created to establish up to 4 severity levels for each indicator, their metrics, and the range of metric values applicable for nursing home residents: level 1 , level 2 , level 3 (severe and worrisome derangements), and level 4 . Equivalence sets were scored only once using the most abnormal indicator level during a specified time window to eliminate double scoring. Also, the most severe score of one or more indicator observations during a specified time window was used only once . The choice of severity levels was based on unsupervised methods using expert clinical judgment, literature, and clinical textbooks . An expeThe final step in NHSI-PrI development involved validity testing. Secondary data from nursing home EHR, MDS, and Risk Management System data were used to validate the NHSI-PrI. The most commonly used measure in the United States to predict PrI risk, the Braden score , was exaA unique feature of the NHSI-PrI development used automatic severity scoring based on EHR, MDS, and Risk Management System data avoiding manual time-consuming abstraction. A computer algorithm was designed to generate the 4 severity levels according to extent of abnormality: the more abnormal the resident attributes, the higher the severity indicator levels and the NHSI-PrI’s severity dimension scores.Categories of EHR data used were vital signs, MDS elements, laboratory test values, and nursing point-of-care activities of daily living documentation. Data were extracted directly from EHRs with computer algorithms (code) created with SAS version 9.4 (SAS Institute Inc) . All eleNursing homes conduct laboratory tests and other assessments infrequently, and enough time is needed to have sufficient data when resident clinical severity is most likely related to the outcome of interest. Also, residents’ severity measure comparisons depend on the standardization of an exposure window for the amount of time a person is observed and at risk for the outcome of interest. An exposure time window should reflect the period during which its effects are relevant to the specified outcome. Important factors to consider when defining exposure are the length of time, changes in exposure status, and consistency and accuracy of exposure measurements. Frequency, format, and intensity of residents’ observations are other important considerations. Clinical judgment was used to establish a 92-day window prior to the first PrI, which was a similar period to the typical quarterly Braden score and other resident assessments. For residents who did not develop PrIs, severity scores were based on indicator values during the final 92 days before discharge  from the nursing home or the end of the study period since residents are often sickest when they are older.t tests or chi-square tests as appropriate. A resident’s most severe Braden score (Worst-Braden) occurring during the 92 days prior to PrI development, discharge/death, or end of the study period was used to define risk categories of low (19-23), mild (15-18), moderate (13-14), and high (10-12). Validation methods included correlations overall and by Worst-Braden risk category followed by logistic regression models with/without severity dimensions to generate propensity scores or probabilistic estimates that a resident develops a PrI. Predictors (independent variables) included NHSI-PrI dimension scores and Worst-Braden score. The goal of these analyses was to assess the predictive capacity of three models: model 1 based on Worst-Braden scores alone, model 2 based on four NHSI-PrI dimensions, and model 3 based on Worst-Braden scores plus four severity dimensions.Descriptive statistics  were used to describe demographic and clinical resident attributes with/without PrIs and were compared using 2-tailed Goodness of fit for logistic regression models was assessed in several ways. First, the overall models (relationship between the independent variables and the dependent variable) were assessed using a C statistic with a minimum value of 0.50 corresponding to chance and a maximum value of 1.0 (perfect prediction). To test the significance of improvement in fit after adding severity dimensions to the model, differences in C statistics between models with/without severity were examined using a likelihood ratio chi-square test. Second, the significance of each severity dimension was assessed by examining odds ratios (ORs) to determine the relative amount by which the odds of the dependent variable increased (OR≥1.0) or decreased (OR<1.0) when the value of the corresponding dimension variable increased by 1 unit. Third, the predictive accuracy or discriminating ability of the models was evaluated using propensity stratification. Observations were divided into equally sized strata defined by deciles of their sorted propensity scores to examine which model best discriminated between residents with/without PrIs. As a final validation of the NHSI-PrI, the study sample was randomly divided into a 65% training data set and a 35% validation data set, and the same validation statistics specified above were computed for each data set.There were 1015 residents in 9 nursing homes during the study period who met the study inclusion criteria and had comprehensive EHR data in the relevant 92-day window for risk of PrI development. Across all 9 nursing homes, between 2.3% (n=3) to 18.3% (n=31) of residents developed PrIs for a total of 8.8% (n=89) having PrIs during the study period.Different severity dimensions were associated with PrI development in residents classified by each of the Worst-Braden risk categories . The higP<.001).The C statistics from three logistic regression models captured the magnitude of improvement associated with adding severity dimensions to predictive models starting with the Worst-Braden score alone . Age, geThe magnitude of this improvement is best gauged by examining the ORs of the individual severity dimensions. For model 3, an increase of 5 points in the locomotion dimension score increases the likelihood of PrI by 75%. A 5-point increase in the underweight dimension score increases the likelihood of PrI by 50%.Laboratory dimension3/uL), lowest female hemoglobin , lowest female hematocrit , lowest male HGB (g/dl), lowest male HCT (%)Lowest platelets (101c (n x norm)Highest glucose (mg/dl), highest hemoglobin AHighest/lowest potassium Highest blood urea nitrogen (mg/dl), highest creatinine (mg/dl), lowest albumin (mg/dl)Highest aspartate transaminase , highest alanine transaminase Highest sodium , lowest sodium (mEq/L)Highest 24 hr urine protein (mg/dl), highest urine protein via dipstick2 saturation on pulse oximetry (%), arterial blood gases, lowest pH (no units), lowest pO2 (mm/Hg), highest pH (no units), lowest total venous CO2 (mEq/L)OHighest white blood cell count , highest bands (%), lowest WBC (k/cu mm)Lowest lymphocytes (%)Highest total bilirubin (mg/dl)Highest total calcium (mg/dl)Highest alkaline phosphatase (u/l)Underweight dimension2BMI <18.5 kg/mWeights, vitals, pain dimensionInfiltrates/consolidation in lungs, rales/rhonchi/wheezes, dyspnea, breath sounds, kussmaul breathing, sputum/secretionsHighest temperature, rigors/chills, lowest temperatureHighest pulse rate, electrocardiogram rhythm, highest blood pressure systolic, highest blood pressure diastolic, lowest pulse rate, lowest systolic blood pressure, orthostatic blood pressureWeight loss, cachexia, weight gain, general painPulse characteristicsChest painLocomotion dimension Locomotion OFF unit with wheelchairLocomotion OFF unit with wheeled reclinerLocomotion OFF unit one person assistLocomotion OFF unit total dependenceLocomotion ON unit one person assistLocomotion ON unit total dependenceThe histogram in The outcome of PrI development was also used to validate the NHSI-PrI results for training and validation data sets. The randomly selected training data set contained 56 PrIs in 658 residents, and the validation data set contained 33 PrIs in 357 residents. For training data, the corresponding predicted C statistics were 0.618 (model 1), 0.717 (model 2), and 0.735 (model 3), resulting in an 18.9% improvement from model 1 to 3. For validation data, the C statistics were 0.648 (model 1), 0.810 (model 2), and 0.816 (model 3), resulting in a 25.9% improvement from model 1 to 3.Multiple different approaches were used to validate the NHSI-PrI to predict residents at risk for PrI development. Model statistics improved from using the Worst-Braden score alone (C=0.627) to using NHSI-PrI alone (C=0.725) to combining the Worst-Braden score and NHSI-PrI (C=0.748). Looking at propensity score deciles versus actual results also validated the improvement indicated by NHSI-PrI. Finally, randomly dividing the data into training and validation data sets showed that the training values had similar corresponding C statistics for Worst-Braden scores alone versus NHSI-PrI alone versus the combination of the two.Measuring resident clinical severity and predicting a specific outcome such as PrI involves an examination of numerous resident attributes  and potentially hundreds of data points. Using existing and relevant data, nursing home outcomes can only be evaluated accurately when pertinent resident attributes that impact the resulting outcomes are included. There is no way to demonstrate whether differences in outcomes are associated with either health interventions, differences in clinical severity, or both if critical aspects of a resident’s clinical severity are not included.Clinical severity in nursing home residents is challenging to define given the multitude of factors affecting the overall health status of older adults who are potentially further compromised by residing in a nursing home . SignifiMultiple different data sources with varied recording formats and coding patterns for the same indicator were encountered in developing and programming the new NHSI-PrI measure, making synchronization of data elements challenging. Yet, it was required to avoid subsequent issues interpreting analysis results.The new NHSI-PrI measure has two unique features: (1) capacity for automatic scoring and (2) daily calculation. First, the NHSI-PrI was designed by clinical experts to be scored automatically from downloaded structured EHR data including vital signs, MDS data elements, laboratory test values, weights, etc. Second, the NHSI-PrI measure can be calculated daily based on findings during the most recent prior 92-day time window, allowing for evolving clinical severity changes to be monitored over time.There is a substantial benefit to identifying and monitoring known PrI predictors and improving prediction using electronic data in addition to the existing Braden score. Little is known about differences in who does and does not develop a PrI, especially among nursing home residents. PrI prevention efforts are well established according to international guidelines, yet PrI incidence has remained high in nursing homes. Historically, clinically assessed PrI risk among residents has resulted in most preventive resources being allocated to residents evaluated at moderate or high risk. However, significant numbers of PrIs also occur in residents in low and mild Worst-Braden risk categories . This reThis study had several limitations that may affect the reproducibility and generalizability of results. First, nursing home populations have several unique characteristics that provide challenges for identifying comparable discrete times of exposure or defined time frames. For example, it was assumed that residents’ exposure time had a clearly defined start and end date when in fact this varied across residents. An up to 92-day window was determined to be most clinically relevant and applied to define exposure duration to measure and compare clinical severity for residents with and without PrIs. Results may differ if shorter or longer time windows are applied. The approach used in computing the NHSI-PrI directly from downloaded structured electronically available data may have limited the variety of indicators that could be included in the NHSI-PrI and may need updating as more relevant structured electronic data become available.Second, our models are not directly linked in real time to measures for risk mitigation. This is due to the fact that clinical severity data in nursing homes are captured less frequently than ongoing clinical appraisals in other settings. Some observations that may be useful predictors are recorded only every quarter. This limits the precision of risk indicators that can be used. More frequent measurement of relevant severity clinical indicators would likely improve the predictive ability of NHSI-PrI.Substantive strides are needed to standardize health care data to facilitate process improvements in data interpretation for future studies. Determination of severity levels required complex data interpretation from various sources for which there is currently no data field standardization. The substantial amount of coding across electronic data formats was a fundamental challenge. Data values needed to be converted to equivalents and interpreted for descriptive data fields to assign severity levels. Data standardization and interpretive processes were carefully performed, checked, and further evaluated taking clinical judgment into account. This process required significant effort to minimize inconsistencies.Finally, the effectiveness of the NHSI-PrI using a larger sample of nursing home facilities and residents is unclear. Our sample was divided into training and validation data sets, each of which well represented the whole data set to test generalizability. Larger confirmatory studies with a different cohort of nursing home residents and facilities should establish the reliability and validity of the new NHSI-PrI and its results.The newly created NHSI-PrI was successful in developing a meaningful profile of clinical severity among nursing home residents and accurately predicting the risk of PrI development. Findings support that clinical severity dimension scores can be used in combination with Worst-Braden scores to augment PrI prediction and potentially impact the quality of care decisions aimed at improving individual PrI prevention plans.


Contamination of ventriculoperitoneal shunts (VPS) by cutaneous flora, particularly coagulase-negative staphylococci, is a common cause of shunt infection and failure, leading to prolonged hospital stay, higher costs of care, and poor outcomes. Glove contamination may occur during VPS insertion, increasing risk of such infections.We performed a systematic search of the PubMed database for studies published January 1, 1970, through August 31, 2021 that documented VPS infection rates before and after implementing a practice of double gloving with change or removal of the outer glove immediately prior to shunt insertion.Among 272 reports screened, 4 were eligible for review based on our inclusion criteria. The incidence of VPS infection was reduced in all 4 quasi-experimental studies with an aggregate incidence of VPS infection of 11.8% before the change in intraoperative protocol and 4.9% after protocol change. One study documented reduced hospital stay with this change in protocol.The risk of VPS infection is reduced by removal or replacement of the outer surgical gloves immediately prior to intraoperative insertion of a VPS as part of an infection control bundle. Many VPS infections are due to skin flora, particularly Staphylococcus epidermidis and S. aureus. VPS infection risk has been associated with male sex, low socioeconomic status, young age (≤18 years old), diabetes, previous VPS revision or infection, type of hydrocephalus, myelomeningocele, use of intraoperative single-glove technique, intraoperative duration of VPS insertion, number of surgeons and experience of surgeons performing VPS insertion, and postoperative CSF leak.Ventriculoperitoneal shunt (VPS) insertion is a common neurosurgical procedure and firstline treatment for chronic hydrocephalus. Incidence of VPS infections varies from <1% to 20%, Strategies used to prevent VPS infection include preoperative use of chlorhexidine shampoo, cutaneous antisepsis , rigorous aseptic technique, limiting shunt contact with the patient’s skin during insertion, using instruments to handle the shunt intraoperatively, a no-shave policy, hematoma prevention, and laparoscopic VPS placement.Management of VPS infection entails shunt removal and antibiotic treatment, and such infections may lead to shunt failure, prolonged hospitalization, neurological disability, increased hospital cost, and higher mortality. Moreover, removing or changing the outer glove immediately prior to handling the VPS may further reduce infection risk, but the significance and magnitude of this effect has thus far been variable. In this literature review, we have summarized available evidence for surgical personnel to remove or change their outer gloves prior to handling shunt instrumentation.VPS infection risk can be significantly reduced by double gloving for shunt insertion and manipulation. PubMed was used to search for articles in any language published January 1, 1970, through August 31, 2021 using the following search terms: surgical infection glove change (261 articles), shunt glove change (9 articles), and shunt infection glove (17 articles). Bibliographies of articles investigating outer-glove removal or change during CSF shunt placement were also searched, producing an additional 6 articles not previously identified, leading to a total of 272 identified articles after 21 duplicates were removed. The methods sections of all full-text articles were assessed for eligibility. Studies were included if a control group was used to compare the CSF shunt infection rates following placement with or without intraoperative removal or change of the outer pair of double gloves immediately prior to handling the shunt before insertion. Studies were excluded if there was no comparison of outer-glove removal or change to no glove removal or change, or if only qualitative comparative results were provided. The primary outcome measure for all included articles was a VPS infection. Of the 245 full-text articles identified among the 272 identified records, 18 addressed glove protocol in VPS placement. Of these 18 records, 14 were ineligible for not specifically documenting intraoperative outer glove removal or change immediately before VPS manipulation as a process measure. Ultimately, 4 studies met the inclusion criteria  guidelines.We identified 4 quasi-experimental, single-center studies involving 934 patients of all ages. The second study retrospectively assessed VPS infection rates in 2 consecutive cohorts of a neonatal population (aged <1 month) undergoing shunt insertion surgery. The authors used an intraoperative infection prevention bundle in for the second cohort with the addition of an adhesive sheet to the skin after draping and double gloving with the removal of the outer-glove layer before handling the shunt. The procedure was completed with a single glove layer. The third study retrospectively assessed VPS infection rates in 2 consecutive cohorts of an adult population (aged >18 years) undergoing shunt insertion surgery before and after implementation of an outer-glove change protocol. These investigators used an intraoperative infection prevention bundle for both cohorts; however, in the second cohort, the investigators added a change of the second glove layer before handling the shunt materials. The final study retrospectively assessed VPS infection rates in 2 consecutive cohorts adult patients undergoing shunt insertion surgery before and after implementation of an intraoperative infection prevention bundle that included replacement of the outer glove layer prior to handling shunt materials.One study prospectively assessed VPS infection rates in a pediatric population (aged <18 years) undergoing shunt insertion surgery after implementation of an intraoperative infection control protocol that included removal of the outer gloves prior to VPS insertion, completing the procedure with a single glove layer. Outer-glove change was also associated with shorter hospital length of stay. A significant decrease in the likelihood of VPS infection was also observed with outer-glove change at 6-month follow-up in a subgroup of patients who underwent first-time VPS insertion after adjusting for the cause of hydrocephalus  and 4.9% after the protocol change (23 infections among 469 patients). Of the 4 studies, 2 reported a significant difference in the incidence of VPS infections with and without intraoperative outer-glove removal prior to VPS insertion . In 1 study, standardizing glove change 1 hour after initiating surgery resulted in a 10% absolute reduction in glove contamination. During VPS insertion, one group of investigators found that contamination of sterile gloves occurred within 15 minutes of donning and recommended that ‘a simple measure would be to change the outer pairs of gloves before handling of the shunt material during surgery.’ Unsurprisingly, outer-glove change prior to handling instrumentation during lumbar fusion led to an 86% reduction in postoperative infections. Nevertheless, more data are needed with glove change alone to prove its utility as a standard of care for all procedures involving implantation of permanent devices.Glove change before handling vascular grafts and cardiac implantable electronic devices has been demonstrated to reduce glove contamination. whereas the 3 others assessed intraoperative glove change as part of an infection prevention bundle. In the lone study that assessed glove change alone, the reduction in VPS infection rate only reached statistical significance at a 6-month follow-up. As such, the attributable effect of outer-glove removal alone is likely contributory to lower infection rates, but further research is needed to unequivocally confirm the impact of this preventative strategy.Our review has a number of limitations. Publication bias is possible due to the small number of studies that met our inclusion criteria. Heterogeneity of the studies was high, and the studies were underpowered. One study assessed only intraoperative glove removal or change,In conclusion, reducing risk of a VPS infection may be achieved through a low-cost protocol of standardizing outer-glove removal or change as part of an infection control bundle prior to handling of the shunt during intraoperative insertion. Replacing the outer glove may be preferable in the event that the inner glove was contaminated due to unsuspected outer-glove perforation during a surgical procedure or during outer-glove removal. This intervention does not require purchase of new equipment, is easy to implement, and can be utilized in resource limited and well-resourced settings.


Species translocation is a popular approach in contemporary ecological restoration and rewilding. Improving the efficacy of conservation translocation programmes requires a combination of robust data from comparable populations, population viability modelling and post-release monitoring. Biotelemetry is becoming an ever more accessible means to collect some of the high-resolution information on the ecology and behaviour of founding populations that such evaluations require. Here, we review 81 published case studies to consider how this capability could increase the success of avian translocations. We found that 67 translocations favoured traditional radio telemetry, with surveillance focussing mostly on immediate post-release dispersal, survival and breeding attempts. Just 28 projects tracked founder individuals for longer than 1 year and no studies referenced pre-release sampling or planning using biotelemetry. While our review shows that tracking devices have been deployed extensively in translocation projects, its application has been mostly limited to short-term spatial and demographic monitoring. We conclude that biotelemetry is a powerful tool for harnessing a multitude of lifetime eco-behavioural data which can be used to build valuable predictive models and surveillance programmes, but this capability has yet to be fully realised by researchers in avian translocations.The online version contains supplementary material available at 10.1186/s40462-022-00359-w. Human activities are leading to a global extinction crisis , with soAlthough motivations and aims for undertaking conservation translocations vary, they can be generally classified across a spectrum comprising population reintroduction, reinforcement and trophic wilding through to ecological replacement, assisted colonisation and community construction, as detailed in Table Historically many translocations have failed, often quite inexplicably at the time, prompting conservation scientists to call for wider implementation of appropriately planned and funded research and post release monitoring programmes to help improve outcomes and understanding of likely causes of failure , 25. BubBiotelemetry has become an ever more powerful and accessible means to gather much of the detailed information required for the effective evaluation of translocation projects . TrackinModern biotelemetry could play a significant role in pre-release and post-release monitoring studies, not least because it is capable of detecting more subtle parameters such as individual decision-making and personality, which command a superior understanding and management of the likely dynamics being played out in translocated populations . TherefoA comprehensive search for articles on avian translocations published between 2005 and 2021 was conducted using Thomson Reuters Web of Science and Google Scholar databases. A publication year threshold of 2005 was applied to reduce bias from historic deployment of heavier tags on larger species. We identified full articles (reviews were excluded) using the topic search terms and Boolean Operators translocat* OR reintro* OR re-intro* AND bird OR avian OR raptor from journal categories of ornithology, ecology, biodiversity conservation, environmental sciences, zoology and biology. Of the 325 relevant papers generated, we excluded translocations that did not report the use of biotelemetry, producing 81 papers for detailed case study review. For each retained paper, we documented the main tracking technologies deployed and key demographic and ecological parameters likely to be important for translocation assessment and monitoring. For further background on these factors, we refer the reader to an overview of biotelemetry hardware and use in ecology study  range of 27 g–16 kg across 29 families, providing both taxonomic breadth and a cross-section of typical tracking technologies available to researchers during the study period.Of the 81 translocations reviewed (noting that some projects deployed multiple types of devices), the majority (67) favoured traditional radio transmitters, manually triangulating bird locations via hand-held receivers. Of the remainder, 18 projects deployed satellite Platform Terminal Transmitters (PTT’s) and four used tags that transferred data via the Global System for Mobile communications (GSM). Just 14 studies utilised Global Positioning System (GPS) enabled devices, while only one project fitted Global Location Sensor (GLS) loggers. Notably, no case studies referenced deployment of tags with additional on-board sensors such as accelerometers.For the majority of studies, capturing demographic responses to translocation was the primary driver of monitoring effort. For example, the majority of translocations documented survival (61), and over half identified causes of mortality (42) and first breeding attempts (42). Importantly, just one quarter measured key data such as productivity (24). While 28 projects monitored founders for longer than 1 year, only a handful of studies reported longer term breeding information such as natal and breeding dispersal distances . As for broader ecological monitoring, a large proportion of studies assessed immediate dispersal from the release location (60), although other spatial-based parameters such as home ranges (28) and habitat selection (20) were examined to a lesser degree. Just eight translocations were able to monitor at sufficient scales to record population ranges (eight) and only six gathered data on migration routes. Group interactions were poorly monitored with just nine translocations recording any kind of social behaviour. Three papers evaluated tag or harness effects and no studies referenced pre-release data collection using biotelemetry, despite a small number of translocations being experimental or exploratory in nature.Biotelemetry is helping to transform ecological and behavioural research, and with at least 81 published cases since 2005, our review shows clearly that tracking devices have been widely deployed in avian translocations . HoweverIt is important to note that there is an inherent risk to each study animal whenever a tracking device is attached . TherefoHolistic understanding of founder ecology and behaviour prior to embarking on a release programme is key to predicting the future dynamics of a translocated population , 8. ModeModern biotelemetry provides the opportunity to harvest such essential data, continuously and remotely on many individuals over multiple years , 42. YetAlthough conducting specific pre-translocation research may not always be feasible , with increasing efficacy of remote tracking and interest in conservation translocations for more widespread species, biotelemetry has a much greater role to play in data collection for planning purposes .High quality information and analyses that informs project design, monitoring and adaptive management can only improve overall likelihood of translocation success . PopulatBefore embarking on a main programme, scientifically robust trials or experimental releases can help remove potentially flawed prior assumptions of founder ecology, a factor which has frequently hampered the effectiveness of translocations historically . WhetherIt is common practice  to provide supplementary food for founders over extended periods at the release site or within the wider landscape, not only to promote optimal long-term health but also to serve as a population management tool, for example, to encourage fidelity to a specific area . MeasuriNew tracking technologies can provide remote and enhanced detection of early breeding attempts, especially for secretive individuals or species that nest in isolated locations , 43. ThiWhile around quarter of the case studies we reviewed captured initial home ranges of translocated birds, most were too brief to measure longer-term population responses such as reproductive performance, seasonal changes in habitat requirements and range development. Similarly, the lack of multi-year monitoring in turn prevented data collection on migratory routes, barriers, stopovers and strategies and any potential for studying individual ontogeny was completely foregone. While some case studies considered habitat use immediately after release, very few performed real analysis or characterisation of wider landscape use and or indeed interpolation with remote sensed environmental data. Arguably such knowledge may be considered peripheral over core metrics of dispersal and survival of founders. However, robust measures of whole-life demographic, spatial use, habitat preferences and behavioural ecology are essential for modelling and managing persistence of translocated populations .Post-release monitoring is catch-all term usually describing observations and data collection conducted during translocations, although here we extend the meaning to include a period of surveillance beyond the release phases . PRM proMost translocations take place within human modified landscapes, and their success is often reliant on societal acceptance and support, best achieved through properly planned public and stakeholder engagement programmes . The abiHas biotelemetry helped to improve the overall success of translocations? From the evidence we found, it is hard to draw any firm conclusions. While our case studies show that biotelemetry has been extensively used in translocation projects, its application has been mostly limited to short-term monitoring of dispersal and survival of founders. Reviewed projects mostly favoured radio-based telemetry, perhaps due to lower unit costs of tags and the limited availability of suitable satellite/GSM/GPS devices historically . HoweverWhile flagging potential risks of deployment, we know that contemporary tracking devices can provide a multitude of long-term eco-behavioural measures from which researchers can build predictive models and post-release monitoring programmes, yet this capability awaits more widespread adoption by conservation managers , 42. WitThere is perhaps a negative popular view of the value of conservation translocations arising from historic low success rates and perceived high costs of these interventions . Our revAdditional file 1. Biotelemetry hardware and use in ecological study.Additional file 2. Case studies full record


Ultrasound ablation techniques are minimally invasive alternatives to surgical resection and have rapidly increased in use. The response of tissue to HIFU ablation differs based on the relative contributions of thermal and mechanical effects, which can be varied to achieve optimal ablation parameters for a given tissue type and location. In tumor ablation, similar to surgical resection, it is desirable to include a safety margin of ablated tissue around the entirety of the tumor. A factor in optimizing ablative techniques is minimizing the recurrence rate, which can be due to incomplete ablation of the target tissue. Further, combining focal ablation with immunotherapy is likely to be key for effective treatment of metastatic cancer, and therefore characterizing the impact of ablation on the tumor microenvironment will be important. Thus, visualization and quantification of the extent of ablation is an integral component of ablative procedures. The aim of this review article is to describe the radiological findings after ultrasound ablation across multiple imaging modalities. This review presents readers with a general overview of the current and emerging imaging methods to assess the efficacy of ultrasound ablative treatments. The goal of this review is to characterize imaging methods for monitoring and assessing ultrasound-mediated ablation. The imaging methods are organized in descending order of current clinical application, and we include some promising emerging technologies. Before discussing imaging modalities, we will provide a brief overview of the types and mechanisms of ultrasound ablation.High intensity focused ultrasound (HIFU) is a versatile treatment modality. HIFU is noninvasive and can be steered in real time. The ultrasound parameters employed dictate how the ultrasound wave interacts with tissue , which in turn cause bioeffects such as heating or mechanical destruction, generating varied types of transition zones and mechanisms of tissue death. With a low mechanical index, mechanical effects are minimized, and the targeted tissue absorbs acoustic energy and primarily thermal effects are generated. Thermal ablation is usually induced with a low mechanical index and high duty cycle, resulting in high time-averaged power. Under conditions for thermal ablation, HIFU produces a region of coagulative necrosis approximating the focal spot volume, which is dependent on transducer geometry and central frequency. With a clinical system operating in the low megahertz or hundreds of kilohertz range, this often exceeds Thermal ablation occurs when sufficient thermal dose is delivered to the target tissue to rapidly induce coagulation and necrosis (50–100°C). The extent and rate of tissue damage varies due to such factors as the amount of energy and rate of energy application, the energy absorption and vascularity of the tissue, and the duration of application. Thus, thermal ablation benefits from both real-time monitoring and posttreatment quantification of the extent of tissue death.At higher pressures, HIFU exerts mechanical effects through the production of cavitation bubbles (histotripsy) or microscopic boiling bubbles (boiling histotripsy) , 3. In hIn addition to generating cavitation and boiling bubbles to induce tissue destruction, exogenous microbubbles or liquid perfluorocarbon droplets can be used with lower pressures to mechanically destroy tissue . MicrobuThe physiologic response to HIFU depends on the specific parameter set used  but can be divided roughly into two regimes: 1) thermal and (2) mechanical. For thermal ablation, coagulative necrosis primarily dictates the imaging features. Immediately following thermal ablation, reactive hyperemia is present in the tissue adjacent to the ablated region due to obstruction of blood flow in the ablated tissue. Mechanically ablative regimes rapidly destroy vasculature, leading to significantly decreased perfusion within the ablated region. Reactive hyperemia and inflammation are less common with mechanical ablation due to the very narrow transition zone between ablated and viable tissue. Here, we will examine imaging modalities from the most frequently clinically utilized to emerging techniques. Magnetic resonance imaging (MRI) is the most widely employed imaging modality clinically for the guidance and assessment of HIFU ablation due to its excellent soft tissue contrast and ability to map temperature in real time. X-ray computed tomography (CT) is the second most widely used modality for ablation assessment due to its ability to rapidly acquire volumetric datasets. A summary of the imaging modalities used for assessment of thermal and mechanical HIFU ablation and the radiological findings is provided in Table  thermal Morphological measurements have been used to assess ablation via registration of pre and postablation images. However, dimensional criteria, such as the Response Evaluation Criteria in Solid Tumors (RECIST) , 24, whiRECIST was initially adopted to evaluate the response of solid tumors to cytotoxic agents. However, subsequent advances in therapies including focal ablation, targeted therapies, immunotherapies, and locoregional therapies have led to the development of a modified RECIST (mRECIST) assessment of response. RECIST criteria measure dimensions, mRECIST criteria measure only the enhanced (viable) portion of lesions. Compared to RECIST, mRECIST is a more accurate predictor of response following thermal ablation . Indeed,Contrast-enhanced scans, used to visualize perfused tissue, can detect coagulative necrosis which is often observed as a rim of greater enhancement around the nonenhancing (due to destruction of vasculature) ablated zone regardless of the modality used. Perfusion can be assessed with all commonly used imaging modalities when a contrast agent is used, but the sensitivity varies by modality. The nonperfused volume is often assessed immediately after HIFU to gauge ablation margins; however, the immediate inflammatory reaction, especially when accompanied by reactive hyperemia, may obscure characteristics of viable tumor.The ability to combine assessments of temperature, perfusion, tissue elasticity, and diffusion within an imaging and treatment session leads to the preference of many clinicians to guide therapy with MRI. MRI is the most commonly used modality for monitoring thermal ablation because of its sensitivity to temperature changes even beyond the temperature at which coagulation occurs (unlike ultrasound) and, while CT has similar to superior temporal resolution, MRI does not use ionizing radiation, and thus, real-time scans can be performed continuously without regard to radiation dose limits. The excellent soft tissue contrast of MRI combined with its prevalence of use for procedure monitoring makes it the most commonly used modality for postprocedure assessment.1, T2, diffusion, and susceptibility have all demonstrated the ability to quantify temperature without exogenous contrast [Magnetic resonance thermometry (MRT) based on the proton resonance frequency shift (PRFS) method , 31 is tReal-time MRI has also been explored for the near real-time monitoring of histotripsy by sensitizing bipolar gradients to the lifespan of the induced bubble cloud , which pMR-ARFI uses micron-scale ultrasonic displacement of a small focal region within the MR image to assess the tissue displacement –35. MotiMRI provides excellent soft tissue contrast through a variety of mechanisms. Endogenous contrast mechanisms available in MRI include differences in the longitudinal relaxation time (T1), transverse relaxation time (T2), proton density (PD), and local changes in the diffusion of water. Additionally, exogenous contrast agents may be used, most often gadolinium chelates or iron nanoparticles. The most common MR method to assess ablation is perfusion-based, contrast-enhanced fat-suppressed T1w imaging. MRI provides excellent monitoring of both the immediate treatment response –42 and lBy far, the most common MR method to assess ultrasound ablation is gadolinium contrast-enhanced T1-weighted (T1w) imaging. In addition to comparing to pretreatment contrast-enhanced T1w images  of ~0.5 HU per °C . Given tHowever, CT is relatively widely employed for postprocedure assessment of thermal HIFU ablation due to its speed and availability. Similar to MRI, a contrast-enhanced scan that assesses perfusion is the most common CT technique employed to assess both thermal and mechanical HIFU ablation since both ablative techniques rapidly disrupt vasculature. Preprocedure CT images visualizing the tumor to be ablated  CT is finding new uses in assessing thermal ablation. Although not used widely for postprocedure monitoring of HIFU, it has been increasingly explored for use postradiofrequency ablation and thus shows promise in being applied to HIFU. DECT uses photons of different energies  and can discriminate between material compositions within each voxel when material decomposition is applied. DECT generates more specific information than Hounsfield units; by assuming that each voxel within the image can be decomposed into a water signal and an iodine signal, DECT generates virtual noncontrast (VNC) images and contrast-only (iodine only) images . The iodine-only images quantify the distribution of the contrast agent and can delineate margins of thermal ablation. DECT is advantageous since a single acquisition can generate both a VNC image and a blended image, reducing radiation exposure compared to traditional CT which requires pre and postcontrast acquisitions. However, DECT is not a replacement for a dynamic scan. Volumetric iodine concentration, derived from DECT, predicts therapeutic response in preclinical models . In the Photon-counting CT scanners are now on the horizon and have the potential to improve the assessment of ablation in several ways. First, the spatial resolution is expected to improve due to the smaller size of the photon-counting detector chips as compared with current detectors. Second, the detectors will estimate the energy of each photon, potentially improving spectral CT from 2 to 4 energy levels. Third, the accuracy of the Hounsfield unit estimates is expected to improve. Finally, the radiation dose can potentially be reduced up to 50% .CT is not used for real-time monitoring of HIFU procedures clinically, but contrast-enhanced CT is relatively commonly used for postprocedure assessment, with thermally or mechanically ablated tissue presenting as nonperfused regions.Thermal HIFU is not often guided by ultrasound imaging primarily due to the shortcomings of ultrasound thermometry. Due to the nonlinear dependence of the speed of sound and other tissue parameters, ultrasound thermometry cannot be accurately applied at temperatures above ~50°C; thus, accurate measures of thermal dose cannot be obtained during ablative therapies. However, ultrasound guidance of mechanical HIFU, such as histotripsy, has demonstrated good success. In a preclinical model, ultrasound-guided histotripsy of the liver in a porcine model demonstrates that compared to pretreatment imaging  imaging or shear wave elastography (SWE). US-ARFI imaging has predictive value preablation in uterine fibroids . UltrasoIn addition to tissue stiffness, contrast-enhanced ultrasound using microbubbles can guide ablation , 94 and Ultrasound is an inexpensive, real-time, point of care imaging modality, but it has not been as widely employed for post-HIFU monitoring. Ultrasound imaging has been limited by the lack of volumetric imaging on current systems, which makes quantification of morphological markers of response such as RECIST challenging. Although several quantitative ultrasound techniques have been proposed, a move to 3D imaging through large aperture, high channel count arrays would dramatically improve biomarker quantitation.The wide availability and real-time nature of ultrasound make it well-suited for guiding and assessing interventional treatments. Greyscale b-mode has been explored for peritreatment monitoring and for posttreatment quantification of the ablated volume. On b-mode, the ablated region often appears diffusely hyperechoic  and can Color Doppler ultrasound discriminates between vascularized and nonvascularized tissue and has shown utility in evaluating the nonperfused volume following ablation , 107. InUltrasound is commonly used for real-time monitoring of histotripsy due to its high frame rate and sensitivity to cavitation bubbles. It is not widely employed for thermal HIFU monitoring due to the nonlinearity of US-derived temperature measurements prior to and following tissue coagulation. US is not widely used clinically for postprocedural assessment. However, both color Doppler and contrast-enhanced US are promising methods that may see increasing use clinically as 3D US imaging methods are improved.18F-fluorodeoxyglucose (18F-FDG) can provide both metabolic and morphological data. As a metabolic marker, 18F-FDG PET imaging immediately postablation does not always present with an inflammation-based hyperintense rim around the ablated zone [18F-FDG PET may be indicative of remaining viable tumor as opposed to reflexive hyperemia. Furthermore, a hyperintense rim on 18F-FDG PET may develop days to weeks later, but this is due to increased glucose metabolism as tissue regenerates.While positron emission tomography (PET) is widely used clinically for imaging solid tumors and in providing quantitative measures of response to therapies, it has not been widely used in HIFU ablation assessment. PET imaging involves the injection of a positron-emitting radioisotope, a variety of which are available that can be incorporated into many molecules of biological interest. Due to the comparative lack of background signal, PET has extremely high sensitivity and signal to noise. However, spatial resolution is reduced compared to other modalities. Tracers such as ted zone  as in ot18F-FDG PET immediately following ablation can accurately predict treatment efficacy [18F-FDG PET imaging has minimal correlation with local tumor progression and disease-free survival [18F-FDG PET to have higher sensitivity (84.6%) than CT (53.4%) for disease progression while both (92.4% for PET and 95.7% for CT) had similar specificities [18F-FDG PET pre-HIFU  followed by a second (~2/3 diagnostic dose) postablation tracer injection. The lower pretreatment dose will have decayed somewhat  prior to administration of the second dose. A pretreatment image is acquired with the initial dose of tracer and the second dose is used to acquire a second, postablation image. The two acquisitions are registered and used to assess the extent of ablation [18F-FDG by liver parenchyma makes this method well-suited to assessing the extent of ablative therapies in the liver. However, due to contraction of the tumor during ablation, in some tissues, a split-dose protocol may have trouble discriminating ablation margins [18F-fluorodihydroxyphenylalanine (18F-FDOPA) has been employed for ablation guidance and postablation efficacy with good results in a preliminary clinical study [An emerging area of PET for monitoring and assessing thermal ablation is split-dose ablation , 115–117 margins . In neural study .18F-FDG [13N-ammonia [15O-water has been evaluated to directly track the behavior of water during repeated thermal dose administrations [13N (~10 min) and 15O (~2 min) allow their repeated use to monitor and delineate ablation margins prior to ending an intervention. While this method has potential application in HIFU ablation given it can quantitatively delineate nonperfused regions, it is most applicable postprocedurally.Another emerging PET technique is combined metabolic and perfusion. This method has not been used in HIFU ablation as yet, but the combination of 18F-FDG  and 13N--ammonia  during itrations . The sho18F-FDG PET image is acquired prior to treatment  makes re-administration impractical during an interventional procedure; nevertheless, a single perfusion image can be obtained with 18F tracers, which may be sufficient for an end of procedure efficacy assessment. Moreover, 18F tracers do not require an on-site cyclotron, increasing their availability.In perfusional PET imaging, an initial While much less commonly used than MRI and CT, PET is seeing increasing use clinically for postprocedural thermal ablation assessment. Currently, we are not aware of any studies evaluating PET’s ability to assess mechanical HIFU, but tracers that assess perfusion are expected to delineate nonperfused mechanically disrupted regions.We have described the common imaging characteristics to guide and assess thermal HIFU and mechanical HIFU on a variety of different modalities. We have also explored emerging technologies in their preclinical stages or in use clinically but applied to other ablative techniques which could be used to assess HIFU ablation. Across all modalities examined, generally, we have found that lesions are nonenhancing very shortly after ablation when perfusion or blood-pool contrast agents are used with the caveat that a hyperemic rim may appear surrounding the ablation zone. This makes it challenging to immediately assess the extent and margins of ablation.MRI is the most commonly used modality to monitor and assess thermal ablation. Ultrasound is most commonly used for monitoring histotripsy. Assessment of histotripsy ablated volumes has been performed with MRI and CT as well as ultrasound. If multiple intraprocedural assessments are indicated during a thermal ablation procedure, PET tracers that assess perfusion may be preferable to other modalities given the tracer may be administered multiple times safely. However, due to the short half-lives of these tracers, many sites may not have ready access, in which case diffusion-weighted MR imaging would be preferable.Future extensions of the use of imaging to assess ultrasound-based ablation are likely to incorporate methods to assess the impact of the treatment on the potential to activate an antitumor immune response. Some of the assessment methods currently involve repeated biopsy or blood-based markers such as circulating tumor cells or circulating tumor DNA. The thermal and mechanical effects generated by HIFU can enhance tumor antigen release into the blood and lymph –125, and


Extracorporeal cardiopulmonary resuscitation (ECPR) represents last-line salvage therapy for poisoning-induced cardiac arrest but no review has focused on this specific area.This scoping review sought to evaluate the survival outcomes and characteristics of published cases of ECPR for toxicological arrest, with the aim of highlighting the potential and limitations of ECPR in toxicology.Eligibility Criteria.We searched PubMed and Cochrane for eligible papers from database inception to October 1, 2022 using the keywords “toxicology”, “ECLS” and “CPR”. References of included publications were searched to identify additional relevant articles. Qualitative synthesis was used to summarize the evidence.85 articles were chosen: 15 case series, 58 individual cases and 12 other publications that were analyzed separately due to ambiguity. ECPR may improve survival outcomes in selected poisoned patients, although the extent of benefit is unclear. As ECPR for poisoning-induced arrest may have better prognosis compared to from other aetiologies, it is likely reasonable to apply ELSO ECPR consensus guideline recommendations to toxicological arrest.Out-of-hospital cardiac arrest alone may not be sufficient grounds to deny ECPR if effective resuscitation had been promptly instituted. Poisonings involving membrane-stabilizing agents and cardio-depressive drugs, and cardiac arrests with shockable rhythms appear to have better outcomes. ECPR may permit excellent neurologically-intact recovery despite prolonged low-flow time of up to four hours. Early ECLS activation and pre-emptive catheter placement can significantly shorten time-to-ECPR and possibly improve survival.As effects of poisoning may be reversible, ECPR can potentially support poisoned patients through the critical peri-arrest state. Extracorporeal life support (ECLS) arguably represents the last-line rescue therapy for severe near-fatal cardiogenic shock arising from drug intoxication when medical therapy failset al (2022) pointed out in a most recent review article, the indications, timing and outcomes for ECLS in cardiotoxic poisoning – least to say the role of ECPR in poisoning-induced cardiac arrest – remain speculative due to the limited data, heterogeneity and multi-drug nature of most poisonings, and the fact that conducting randomized human trials is virtually impossibleWhile cardiac arrest represents the most extreme case of cardiogenic shock, much less is known about the utility of ECLS for cardiac arrest from drug intoxication during active ongoing cardiopulmonary resuscitation (CPR) – otherwise known as extracorporeal CPR (ECPR). The Extracorporeal Life Support Organization (ELSO) defines ECPR as the application of rapidly-deployed veno-arterial extracorporeal membrane oxygenation (ECMO) in patients in whom conventional CPR is unsuccessful in achieving sustained return of spontaneous circulation (ROSC)Thus far, no systematic review has focused on the role of ECPR specific to drug intoxication and evidence has been purely observational to dateThe objective of this scoping review was to evaluate the survival outcomes and characteristics of published cases of ECPR for poisoning-induced cardiac arrest. Primary outcome of interest was survival. Secondary outcomes were functional outcomes and duration of ECLS support required. Complications from treatment were also documented where reported.All sources including observational studies, reviews, letters, comments, case reports, meeting abstracts and conference proceedings in any language were included without date restriction up to October 1, 2022 when the most recent search was executed. The search was not limited by publication status or by type as relevant literature was already scarce. The search was also not limited to English language to avoid language bias, particularly because several institutions hailing from non-English native-speaking countries like France have amassed considerable experience with ECPR and published prominent landmark articles.Studies were eligible if they involved human cases of poisoning leading to refractory normothermic cardiac arrest. Articles that reported paediatric cases were included if relevant. Studies based on experimental animal models were excluded.Cases of cardiogenic shock without cardiac arrest were excluded. Cases of cardiac arrest confounded by severe hypothermia were also excluded, as the role of ECPR for rewarming in hypothermic cardiac arrests has been firmly established and prognoses and management considerations for accidental hypothermic cardiac arrest differ uniquely.Given the sometimes fleeting and transitory nature of cardiac arrest, cases where there was ambiguity over the temporal sequence of events  were retrieved but analysed separately. This included cases that reported transient ROSC with multiple refractory cardiac arrests, and cases where ECLS cannulation was performed in peri-arrest patients with conventional closed-chest CPR ongoing for agonal low-flow cardiac output.Studies that discuss the role of extracorporeal cardiopulmonary resuscitation were eligible. Based on the ELSO definition of ECPR, cases that focused on the use of veno-venous ECMO (indication being respiratory failure rather than circulatory collapse) and cases of cardiac arrest that were successfully resuscitated with conventional CPR and had sustained ROSC prior to ECLS were excluded.Studies needed to document at least one of the primary or secondary outcomes to be eligible. Primary outcome of interest was survival. Secondary outcomes were functional outcomes and duration of ECLS support required. Complications from treatment were also documented where reported.The authors followed the Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) guideline. This scoping review was not eligible for inclusion in PROSPERO as it constituted a scoping review.The authors accessed PubMed and Cochrane Library to identify eligible papers from database inception to October 1, 2022. A search strategy was developed in conjunction with content experts and librarians, using the following keywords: (toxicol* OR poisoning OR overdose OR intoxica*) AND  AND (cardiopulmonary resuscitation OR CPR OR cardiac arrest OR ECPR) . Other sTwo authors  independently carried out screening for eligibility, blinded to authors and journal names. Differences were resolved by discussion and consensus, or when necessary, a senior third reviewer (RP). All retrieved citations were exported and duplications were removed. Studies were filtered according to inclusion criteria and the authors reviewed the titles and abstracts of all studies before retrieving and reviewing the full texts. A data abstraction form was used to standardize data retrieval after a pilot version was trialled among the data abstractors on three cases. Study characteristics , subject characteristics , treatment characteristics  and outcome characteristics  were independently abstracted by the two data abstractors  for each included study. No significant abstraction differences were found between authors. An independent author (MN) then merged the data into a single database to ensure uniformity. Efforts were made to reach out to the corresponding authors of selected articles where there was ambiguity to make important clarifications. Qualitative synthesis was used to summarize the evidence.In this scoping review, no risk of bias assessment or other assessment of methodological quality was performed on the identified studies.The primary search strategy yielded 201 eligible articles. A further 51 articles were identified to be of relevance based on the references and bibliography of these chosen articles . Three f17 of the articles excluded in Phase Two were review articles – some of which discussed ECLS for poisoning-induced cardiotoxicity in general while others focused on specific poisons. These articles mostly recommended early initiation of aggressive measures like ECLS for poisoned patients with severe cardiotoxicity once standard resuscitative measures have failed, Supplement 1]Of the 85 studies eventually included in the qualitative synthesis, 15 articles were case series [9], [10]Table 218,9-12,9-11,.20,15 case series involving 158 patients were identified. Among the case series, two were from the United Stateset al drew comparisons between consecutive poisoned patients admitted to two university hospitals – one highly-practiced in ECPR, while the other had no access. Masson concluded that ECPR for severe poisoning-induced cardiovascular shock or collapse was associated with lower mortality compared to conventional treatment11,All selected case studies were retrospective observational studies. None of the studies matched cases with controls, although one retrospective observational cohort study by Masson et alet al (n = 71) which found a survival rate of 11 %All 15 case series identified evaluated survival as their primary outcome. ECPR survival rates cited ranged from 100 %et al found similar survival-to-discharge rates for IHCA  and OHCA Three case series51,Virtually all of the individual cases  cases were witnessed IHCAs, although two cases first had OHCA and achieved ROSC with conventional CPR before suffering another IHCA requiring ECPR29,Among the individual cases, 41/58 (70.7 %) involved poisoning by cardiotoxic drugs or membrane-stabilizing agents. They were mostly single-agent intoxications . Low-flow duration (time from cardiac arrest to ECPR) ranged from three minuteset al described a novel approach to the management of life-threatening venlafaxine overdose which involved escalating veno-arterial ECMO to veno-arterial-pulmonary arterial ECMO by introducing a third cannula into the pulmonary artery – this first-in-man, fully-percutaneous complete heart–lung bypass set-upThere have been many advances in ECLS over the past 30 years, increasing the opportunity to use this approach to salvage patients with poisoning-induced cardiac arrests. Up to 1980 s, cardiopulmonary bypass support necessitated median sternotomy to permit right atrial venous cannulationHowever, despite increasing adoption as a last-ditch salvage modality for cardiac arrest in recent years, the evidence for ECPR in the context of poisoning-induced arrests remains limited to predominantly case reports and a few small observational cohort studies. Although reported ECPR survival rates vary widely, a significant number of studies have described instances of functional and neurologically-intact recovery with ECPR. This suggests that optimal patient selection is key and ECPR still shows much promise in the correct carefully selected patient subgroupFor instance, ECPR for cardiac arrest from cardiotoxin or membrane-stabilizing agent poisoning in particular appears to have better prognosis6) in the context of toxicological arrests as well. One could possibly even be more optimistic and aggressive in such poisoning cases, given that one can expect better prognoses than non-toxicological arrest.Three case series separately found that ECPR for poisoning-induced cardiac arrest has better prognoses compared to ECPR for non-toxicological cardiac arrest. The potentially reversible nature of most poisonings means that ECPR support can be used to maintain perfusion and provide circulatory support until the offending drugs are metabolized or eliminated and their effects reversedet al found no differences in survival outcomes between OHCA and IHCA71,Fewer, shorter delays to specialized care are expected in a resource-rich inpatient setting for IHCAs. This anticipation that survival outcomes from IHCA should outdo OHCA has likely led to institutional practices which bias IHCA over OHCA when assessing candidacy for ECPR. It is therefore surprising that Baud et al highlighted that low-flow time (time from cardiac arrest to ECPR) was shorter in survivors compared to non-survivors and recommended that shortening the timing to ECPR initiation ought to be made a key priorityet al and Baum et al in particular reported survival with intact neurological status despite low-flow durations of 240 minutesDuburcq et al described a case of life-threatening caffeine overdose in which low-flow time was only three minuteset al likewise reported nine minutes – in this case, the ECLS team had likewise been consulted early due to refractory hypotension and was already at the bedside when the patient developed sudden ventricular fibrillation arrestet al reported markedly poorer survival for ECLS for poisoning-induced cardiac arrest (42.9 %) compared to poisoning-induced cardiogenic shock (88.0 %)On the other end of the spectrum, Yasuda et al further noted that outcomes for cardiac arrest from sedative-hypnotic overdose were especially dismalCardiopulmonary bypass support for poisoning-induced cardiac impairment was first used predominantly for overdoses from cardio-depressive drugs  and membrane-stabilizing agents (Class I antiarrhythmic agents such as flecainide and bupivacaine)et al described an “on-site” ECPR concept where the patient is promptly cannulated, commenced on ECLS in the emergency room of a peripheral hospital with support from the ECLS team and transferred to the ECLS-capable centre once stabilizedPatients who first presented to a peripheral hospital, arrested and required secondary transfer to an ECLS-capable centre with chest compressions ongoing had outcomes  nearly identical to cases that did not require secondary transfer  . Centreset alet alet al had published a small case series (n = 6) of ECLS for poisoning-induced arrests at Caen between 1997 and 2000et al similarly highlighted his experience at Caen between 1997 and 2003 with cases that required ECLS for prolonged cardiac arrestet al re-explored the use of ECLS in Caen University Hospital again from 2003 to 2013It is noteworthy that criticism has been levelled on Masson This disproportionate over-representation of survival cases from a select few institutions like Caen would amplify bias for ECPR. Although the study findings only reflect the results of ECPR in experienced hands at a single high-volume institution and may thus not accurately parallel the outcomes achievable by other less-practiced institutionsAlthough this review paper focussed on survival and functional outcomes as the primary and secondary outcomes of interest, other outcomes are worth exploring. While complete myocardial recovery is often hoped for, the patient may sometimes still have severe residual cardiac function impairment necessitating further mechanical support from ventricular assist device or even orthotopic heart transplantet al also discussed an unfortunate patient who had flecainide and betaxolol poisoning and succumbed to brain death despite early ECLS. However, ECLS helped maintain vital organ perfusion and permitted successful recovery of the patient’s heart, liver and kidneys for allograft transplantVivien et al used various modelling tools to evaluate its cost effectiveness. Assuming 27 % survival in poisoned cardiac arrest patients treated with ECPR , St-Onge estimated that cost per life year  was less than the $50,000-$100,000 per quality-adjusted life-year gained that was often cited in medical literatureWhile ECPR is resource-intensive and prohibitively expensive, St-Onge et al carefully reviewed the cases from the ELSO registry and noted that prolonged ECMO runs were unlikely to be required specifically for poisoning-induced cardiac arrestWeiner This study represents the first and most current summary of the varied published evidence relating to ECPR for poisoning-induced cardiac arrest specifically. The strengths of this review are the systematic search technique, comprehensive data extraction and in-depth qualitative synthesis. However, this study has several limitations as expected of a retrospective literature review. Case reports and the occasional case series from various authors hailing from different centres of diverse clinical settings have together made up an extremely heterogenous cohort, while the lack of a standardized manner for reporting of events has also limited the ability to analyse findings.8,5,For instance, lack of standardized definitions meant that some authors describe ECMO as a “veno-venous method of providing oxygenation” that was distinct from ECLSMost of the germane articles in existing literature thus far are descriptive case reports and case series without comparisons drawn between ECLS and conventional treatment. This limits the utility of this scoping review to an observational nature. Moreover, the overwhelming majority of published cases reported successful positive outcomes. This is almost certainly due to the combined effects of deliberate and careful patient selection, publication bias and over-representation of successful cases, rather than proof that ECPR is truly a “Hail Mary” panacea capable of miraculously salvaging all patients. To this end, international multi-centre collaborative registries that track both ECPR successes and failures alike are less susceptible to the effects of publication bias and would represent potential areas for future collaboration and research.As poisonings represent a potentially reversible cause of arrest, ECPR may therefore be used to support the patient through the critical peri-arrest period. By maintaining vital organ perfusion, ECPR permits more time for drug clearance to enhance the patient’s chances of survival. Cardiac arrest from poisoning with cardiotoxic agents like beta-antagonists and membrane-stabilizing agents have more published evidence for successful ECPR outcomes. While ECPR is best instituted early as shorter low-flow times yield better outcomes, neurologically-intact and functionally-intact survival have been achieved even after prolonged normothermic ECPR runs of up to four hoursNo funding or sponsorships were received for this study. All of the authors declare that they do not have any competing interests.


Colourful spots, stripes and rings decorate the corolla of most flowering plants and fulfil important biotic and abiotic functions. Spatial differences in the pigmentation of epidermal cells can create these patterns. The last few years have yielded new data that have started to illuminate the mechanisms controlling the function, formation and evolution of petal patterns. These advances have broad impacts beyond the immediate field as pigmentation patterns are wonderful systems to explore multiscale biological problems: from understanding how cells make decisions at the microscale to examining the roots of biodiversity at the macroscale. These new results also reveal there is more to petal patterning than meets the eye, opening up a brand new area of investigation. In this mini-review, we summarise our current knowledge on the Eco-Evo-Devo of petal pigmentation patterns and discuss some of the most exciting yet unanswered questions that represent avenues for future research. Petals show striking morphological diversity across the ∼350,000 species of flowering plants, sometimes even within the same flower. When asked to describe flowers, it is often easiest to detail the differences in their petals. Patterns emerge on the petal surface when different regions of the epidermis develop distinct characteristics. Most petals are not uniformly coloured; some patterns are hidden from us and only detected by animals. Pollinating insects can perceive differences in colour, shape, scent and texture, or a combination of these as well as heat, humidity or even electrical charge gradients on the petal surface . PatternLapeirousia oreogena is highly modified, with pointed tips resembling an arrow [Hibiscus trionum bicolour bullseye is visible to the human eye, with dark anthocyanin pigmentation at the petal base contrasting with cream-coloured flavonols at the tip [Spots are formed by restricting pigmentation to small dots or circles of cells on the epidermis. Petal spots can vary in number, position, size or shape ,16–18. Tan arrow . The pigan arrow , but stran arrow . As seenan arrow  and mothan arrow , venatio the tip . Sunflow the tip . In extr the tip . By combPlant pigments belong to three main categories: flavonoids (red to blue anthocyanins and cream-yellow flavonols), carotenoids and betalains. All three groups participate in petal patterning and are highly diverse with regard to their chemical structures and the colours they produce. The properties of these pigments, along with their synthesis and their physiological and ecological roles, have been extensively studied and recently reviewed . PatternWHITE PETAL1 and Reduced Carotenoid Pigmentation 1 can regulate carotenoid-derived petal colour in Medicago and Mimulus lewisii, respectively [BvMYB1, a highly expressed subgroup 6 R2R3-MYB identified in beetroot, is unclear but it fails to interact with known bHLH partners derived from anthocyanic model organisms [Transcriptional regulators of the flavonoid pathway are well-known: biosynthetic gene expression is mainly controlled by MBW complexes consisting of R2R3-MYB, basic-helix-loop-helix (bHLH) and WD-repeat (WDR) proteins, reviewed in . MYB proectively ,36. MYB ectively : the modrganisms .Petal patterns have long been a source of fascination for scientists from various disciplines. This may be why the functional relevance of those motifs, the molecular and cellular events orchestrating their formation and the evolutionary processes that modify them have often been studied independently from each other. However, the field has gained incredible momentum in the last 15 years. This is in part due to the rapid and widespread adoption of novel technologies but also thanks to powerful model systems well-suited for functional investigations at the bench as well as behavioural studies in the field. Petal patterns are more complex than they may appear to the naked human eye. By taking a multiscale and interdisciplinary approach, it is now possible to start understanding the wealth of fascinating biology, until very recently largely unexplorable, that underlies those multifunctional features. In this review, we attempt to synthesise our current understanding of the roles, development and evolution of the motifs that decorate petal surfaces. We also identify current bottlenecks and gaps in our knowledge, and we propose future strands of research to move the field forward. Finally, we discuss how recent findings position petal patterns as excellent systems to ask essential questions that reach far beyond the biology of petal patterning, allowing scientists to directly explore the inner workings of cells and the basis of biodiversity.Petal patterns are important in pollinator interactions ,38–41. CHemerocallis flowers but for different reasons. Swallowtails prefer H. fulva because of colour contrast within the flower. Hawkmoths prefer H. citrina flowers because of their UV-reflecting bullseye pattern [Pattern-mediated pollinator attraction is well commented on in the literature, but until recently, experimental validation remained scarce. In the 1990s, Dafni and colleagues demonstrated that flowers with a dark centre or with bilaterally symmetric patterns are more attractive to beetles than flowers without a dark centre, or with radially symmetric patterns ,44. We n pattern . Yellow  pattern . In cont pattern . As diffGorteria diffusa, which attracts dipteran flies [Linum pubsecens, which attracts bee flies [Romulea monadelpha, Hesperantha vaginata and Sparaxis elegans, three species pollinated by monkey beetles [Gorteria dark spots was investigated experimentally with artificial flowers: circular discs with central black spots were shown to reduce the inter-floral search time of bumblebees compared with unpatterned orange discs [Pigmentation patterns allow flowers to resemble food-rewarding species  or mimican flies ; Linum pee flies  and Romu beetles . The ecoge discs .Guideless mutants in Mimulus lack yellow floral guides. Not only are fewer pollinator visits recorded for guideless, but the incorrect entry position of visitors likely reduces pollen transfer to the insect’s body [Hypoxis camerooniana pattern alter post-landing pollinator behaviour [The prevalence of venation patterns could reflect their role as pollinator guides , but obst’s body . Experimehaviour , demonstTo date, only a handful of studies have specifically examined how differential visitation associated with colour patterns, rather than with overall flower colour or other well-studied floral traits such as flower size and shape, translates into individual fitness. The findings of those studies indicate that the effect of petal patterning on plants reproductive success varies broadly between species and is likely to depend heavily on the environmental context. For example, Tremblay and Ackerman  found thRecent research suggests that coloured petal patterns could also fulfil functions unrelated to pollination, including response to environmental factors or interactions with pests and herbivores. These alternative functions are perhaps better thought of as additional functions because they may act alongside pollinator interactions.Colourful displays usually produced by flowers are occasionally found on other plant organs: various carnivorous plants display patterns within the UV light range on their trap , a modifSt. John’s wort flowers exhibit a UV pattern on the back of their petals A. This pPetal pigmentation patterns can also fulfil abiotic functions: the size of the UV-absorbing bullseye of silverweed co-varies with UV incidence as populations experiencing higher UV irradiation display a larger UV-absorbing centre  capable Variegation, colour flecks and stripes can occur due to viral infections triggering ‘colour breaks’ and genetic instability caused by transposon activity ,70,71. HDuring petal development, the activities of the transcription factors that regulate pigmentation pathways, cell fate specification and tissue growth are likely to be set by pre-patterns . These pVENOSA and its bHLH partner DELILA. VENOSA is expressed around the vasculature while DELILA transcription is restricted to the petal epidermis, defining a narrow overlapping domain in the epidermal cells overlying the vasculature where partners coexist and activate anthocyanin production [VENOSA expression. This signal could be auxin as VENOSA has two auxin-response element-like sequences in its promoter [Expression of each component of the MBW complex is critical as the complex is only active when all components are present. This provides grounds for emergence of precise pigmentation patterns from broadly defined expression domains. In snapdragon, venation patterning requires the R2R3 MYB oduction   activity along the proximo-distal axis of developing leaves [gif1/an3 mutation also affects petals, yielding shorter, narrower petals [Morphogens can also provide positional information B. This nt manner . Howeverg leaves . The gifr petals ,84. HoweSpontaneous acquisition of positional characteristics without apparent pre-patterns is common in animals and plants ,75,85,86Mimulus guttatus is the product of a two-component reaction-diffusion system involving an R2R3-MYB activator, NECTAR GUIDE ANTHOCYANIN (NEGAN), and the R3-MYB diffusible inhibitor, RED TONGUE (RTO)  and self-organising mechanisms (that act downstream and specify the type of pattern) to add spots to the petal base.The development of red spots in UE (RTO) C. NEGAN ormation . Anthocy tongue’ C. This pModelling approaches are powerful ways to explore pattern emergence, especially as the processes involved are often not intuitive. By combining mathematical models of relatively simple mechanisms, Ringham and colleagues recapitulated a broad range of petal patterns observed across flowers . A theorPigment appearance can change according to their subcellular location and the shape of the cell. Cell shape and cuticle texture constitute tridimensional structures that impact the path of light entering or exiting the cell, modifying the visual aspect of the petal or even producing colours through light diffraction and constructive interference ,91–97. TPetal pigmentation patterns can be gained, lost or experience changes in colouration hue or intensity during evolution. The relative position of pattern elements or their proportions can be altered, and pigmentation patterns can convert from one type into another A. By invR2R3-MYB regulatory genes. Mimulus lewisii flowers display a white ring around their corolla throat, but the resulting picotee pattern is absent in M. cardinalis. Such difference between closely related monkeyflowers is due to cis-regulatory variation that triggers the expression of LIGHT AREAS1, an R2R3-MYB that promotes flavonol production, around the throat margin of M. lewisii [Shifts in colour patterning appear predominantly linked to modified expression patterns of  lewisii .Clarkia gracilis species complex can be distinguished by the position of their petal spot [cis-regulatory rewiring: the position of the spot is governed by distinct alleles of the CgMYB1 gene, whose expression patterns match either the basal (bCgMYB1) or central (cCgMYB1) regions accumulating anthocyanins [bCgMYB1-like allele led to MYB1 losing its ability to be activated by TF-X while becoming controlled by TF-Y , which normally regulates anthocyanin production [M. guttatus populations from Oregon and California show variation in patterning of their yellow flowers, ranging from having a fully red corolla throat (red-tongue bullseye) to a red spotted corolla throat. The transition from spot to bullseye across those wild populations is due to different alleles of RTO, with the red-tongue bullseye morph only carrying non-functional rto alleles [Mutations affecting gene coding regions can also trigger changes in petal patterning. The transition from pink to white in the petal base of oduction . M. gutt alleles  . Similarly, pigmentation motifs acting as post-landing guides could positively affect female fitness  by manipulating the position of the insect body in a way that maximise pollen deposition on stigmata, enhancing the chance of ovule fertilization and seed formation. However, the roads to male and female fitness are complexes: many external factors such as abiotic environmental conditions or the presence of different neighbour competing for animal attention as well as circumstances intrinsic to each species  all play a role and must be accounted for. One of the most exciting challenges for future studies will be to disentangle the contribution, if any, of petal patterns to reproductive fitness and identify precisely, in a diversity of systems, the mechanisms by which colourful motifs can influence pollination success to see if trends can be identified.Petal patterns provide experimental and theoretical scientists with numerous opportunities for collaborative and interdisciplinary work. They also constitute excellent systems to understand how decisions made by minute cells are coordinated at the tissue and organ scale, how the execution of different developmental programs impact each other, and how evolutionary processes and diverse biotic and abiotic factors can drive and shape biodiversity. Thus, studying petal patterns help address fundamental questions of modern biology that reach far beyond understanding how flowering plants paint their surface.Underlying petal pigmentation patterns is a wealth of fascinating biology that until very recently has been largely unexplorable.Petal patterns are multifunctional: they participate in plant–pollinator communication but also mediate interactions with herbivores, protect pollen grains from UV radiation, or enhance resistance to desiccation.Pigmentation motifs coexist with other patterns inconspicuous to the human eye because they are microscopic  or because they are by nature invisible .The petal epidermis is an excellent system to study the dynamics of cellular decision-making processes because the outcomes of decisions made by cells at the microscopic level are readily observable and can directly impact reproductive success at the macroscale.Petal pigmentation patterns can vary between populations and species: they can be lost or gained but also change in shape and dimension during evolution. Those changes can be adaptive with both abiotic and biotic factors able to exert selective pressures. Pattern variations can be used as markers of climate change but also lead to reproductive isolation and speciation.Future research will aim at understanding the mechanisms used by epidermal cells to make decisions, how these decisions are coordinated at the tissue and organ scale, what the origins of regulatory networks that govern petal patterning are and how rewiring of these networks contribute to plant fitness and the creation of biodiversity.


In “Neural Activity During Audiovisual Speech Processing: Protocol for a Functional Neuroimaging Study” :e38407), the authors noted one error.The originally published article appeared with an incorrect Abstract. In the corrected version, the Abstract is updated as follows:Background: Functional near-infrared spectroscopy (fNIRS) studies have demonstrated associations between hearing outcomes after cochlear implantation and plastic brain changes. However, inconsistent results make it difficult to draw conclusions. A major problem is that many variables need to be controlled. To gain further understanding, a careful preparation and planning of such a functional neuroimaging task is key.Objective: Using fNIRS, our main objective is to develop a well-controlled audiovisual speech comprehension task to study brain activation in individuals with normal hearing and hearing impairment (including cochlear implant users). The task should be deductible from clinically established tests, induce maximal cortical activation, use optimal coverage of relevant brain regions, and be reproducible by other research groups.Methods: The protocol will consist of a 5-minute resting state and 2 stimulation periods that are 12 minutes each. During the stimulation periods, 13-second video recordings of the clinically established Oldenburg Sentence Test (OLSA) will be presented. Stimuli will be presented in 4 different modalities: (1) speech in quiet, (2) speech in noise, (3) visual only , and (4) audiovisual speech. Each stimulus type will be repeated 10 times in a counterbalanced block design. Interactive question windows will monitor speech comprehension during the task. After the measurement, we will perform a 3D scan to digitize optode positions and verify the covered anatomical locations.Results: This paper reports the study protocol. Enrollment for the study started in August 2021. We expect to publish our first results by the end of 2022.Conclusions: The proposed audiovisual speech comprehension task will help elucidate neural correlates to speech understanding. The comprehensive study will have the potential to provide additional information beyond the conventional clinical standards about the underlying plastic brain changes of a hearing-impaired person. It will facilitate more precise indication criteria for cochlear implantation and better planning of rehabilitation.The correction will appear in the online version of the paper on the JMIR Publications website on June 28, 2022, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories.