Achieving "nature positive" requires net gain legislation.

Reforms underway in Australia highlight key challenges.

PHARMACOKINETIC PROFILES OF ORAL PHENYLBUTAZONE, MELOXICAM, AND FIROCOXIB IN SOUTHERN BLACK RHINOCEROS (DICEROS BICORNIS MINOR).

The pharmacokinetic profile of selected NSAIDs in southern black rhinoceros (Diceros bicornis minor) were studied. Phenylbutazone (PBZ), meloxicam (MEL), and firocoxib (FIR) were administered orally to five captive, black rhinoceros, and blood was collected at predetermined time points for NSAID quantification and noncompartmental pharmacokinetic (PK) analysis. Phenylbutazone 4.0 mg/kg PO q12h for three doses, MEL 0.3 mg/kg PO q24h administered twice, and a single oral dose of FIR 0.1 mg/kg, were tested with a minimum washout time of 2 wk. PBZ reached a median (range) peak concentration (Cmax) of 9.42 (2.74-11.5) g/ml at a mean (range) time (Tmax) of 6.00 (4.00 to >12.00) h, and the median (range) elimination half-life (T1/2) was 6.07 (3.95-6.49) h. Phenylbutazone pharmacokinetic parameters for black rhinoceros in this study were similar to domestic horses. Meloxicam reached a median (range) Cmax of 0.576 (0.357-0.655) µg/ml at a median (range) time (Tmax) of 6.00 (4.00-12.00) h; the median (range) T1/2 of MEL was 14.0 (12.4-17.9) h. These results demonstrate that once-daily administration of MEL at 0.3 mg/kg resulted in a serum concentration of greater than 0.200 µg/ml from 2 to 24 h in four animals, which is within the analgesic range (0.200-0.400 µg/ml) for this drug in other species postulated by other studies. A single dose of firocoxib (0.1 mg/kg) reached a median (range) peak concentration (Cmax) of 15.7 (9.65-17.3) ng/ml at a median (range) Tmax of 4.00 (4.00-6.00) h. The median (range) elimination T1/2 of FIR was 4.96 (4.47-6.51) h, which is faster than in the horse. The data suggest that extrapolation from equine FIR dosage recommendations is inappropriate for black rhinoceros.

DNA damage-associated protein co-expression network in cardiomyocytes informs on tolerance to genetic variation and disease.

Cardiovascular disease (CVD) is associated with both genetic variants and environmental factors. One unifying consequence of the molecular risk factors in CVD is DNA damage, which must be repaired by DNA damage response proteins. However, the impact of DNA damage on global cardiomyocyte protein abundance, and its relationship to CVD risk remains unclear. We therefore treated induced pluripotent stem cell-derived cardiomyocytes with the DNA-damaging agent Doxorubicin (DOX) and a vehicle control, and identified 4,178 proteins that contribute to a network comprising 12 co-expressed modules and 403 hub proteins with high intramodular connectivity. Five modules correlate with DOX and represent distinct biological processes including RNA processing, chromatin regulation and metabolism. DOX-correlated hub proteins are depleted for proteins that vary in expression across individuals due to genetic variation but are enriched for proteins encoded by loss-of-function intolerant genes. While proteins associated with genetic risk for CVD, such as arrhythmia are enriched in specific DOX-correlated modules, DOX-correlated hub proteins are not enriched for known CVD risk proteins. Instead, they are enriched among proteins that physically interact with CVD risk proteins. Our data demonstrate that DNA damage in cardiomyocytes induces diverse effects on biological processes through protein co-expression modules that are relevant for CVD, and that the level of protein connectivity in DNA damage-associated modules influences the tolerance to genetic variation.

Poor compliance and exemptions facilitate ongoing deforestation.

Many nations are struggling to reduce deforestation, despite having extensive environmental protection laws in place and commitments to international agreements that address the biodiversity and climate crises. We developed a novel framework to quantify the extent to which contemporary deforestation is being captured under national and subnational laws. We then applied this framework to northern Australia as a case study, a development and deforestation hotspot with ecosystems of global significance. First, deforestation may be compliant under all relevant legislation, either through assessment and approval or because of exemptions in the legislation. Second, deforestation may be compliant under at least one relevant law, but not all. Third, there may be no evidence of deforestation assessment or exemption from assessment, despite their apparent requirement, which could mean the deforestation is potentially noncompliant. Finally, deforestation may occur in an area or under circumstances that are beyond the intended scope of any relevant legislation. All deforestation that we analyzed was hypothetically covered by one or more laws. However, 65% of deforestation was potentially noncompliant with at least one law. Because multiple laws could be relevant to a given clearing event, the majority of clearing was still compliant with at least one law, but of these events, only a small proportion was explicitly approved (19%). The remaining were permitted under various exemptions. Of all the legislation we analyzed, most of the exempt clearing occurred under one subnational law and most potentially noncompliant clearing occurred under one national law. Our results showed that even a nation with a suite of mature environmental protection laws is falling well short of achieving international commitments regarding deforestation. Our framework can be used to pinpoint the pathways of policy change required for nations to align local laws with these international accords.

Cumplimiento deficiente y exenciones que facilitan la deforestación Resumen Muchos países luchan por reducir la deforestación, a pesar de contar con amplias leyes de protección del medio ambiente y de sus compromisos con los acuerdos internacionales que abordan la crisis de la biodiversidad y el clima. Por ello desarrollamos un novedoso marco para cuantificar hasta qué punto la deforestación actual se recopila en las leyes nacionales y subnacionales. Después aplicamos este marco al norte de Australia como estudio de caso, un punto caliente de desarrollo y deforestación con ecosistemas de importancia mundial. En primer lugar, la deforestación puede ser compatible con toda la legislación pertinente, ya sea mediante evaluación y aprobación o debido a exenciones en la legislación. En segundo lugar, la deforestación puede ser compatible con al menos una ley pertinente, pero no con todas. En tercer lugar, puede que no haya pruebas de evaluación de la deforestación o de exención de la evaluación, a pesar de su aparente requisito, lo que podría significar que la deforestación es potencialmente no conforme. Por último, la deforestación puede producirse en una zona o en circunstancias que quedan fuera del ámbito de aplicación de la legislación pertinente. Toda la deforestación analizada era hipotéticamente legal según una o más leyes. Sin embargo, el 65% de la deforestación no cumplía potencialmente al menos una ley. Dado que varias leyes podían ser pertinentes para un determinado caso de deforestación, la mayoría de las deforestaciones seguían cumpliendo al menos una ley, pero de estos casos, sólo una pequeña proporción estaba explícitamente aprobada (19%). El resto estaba permitido en virtud de diversas exenciones. De toda la legislación que analizamos, la mayor parte de la compensación exenta se produjo en virtud de una ley subnacional y la mayor parte de la compensación potencialmente no conforme se produjo en virtud de una ley nacional. Nuestros resultados muestran que incluso un país con un conjunto de leyes maduras de protección del medio ambiente está muy lejos de cumplir los compromisos internacionales en materia de deforestación. Nuestro marco puede utilizarse para determinar las vías de cambio político necesarias para que los países adapten su legislación local a los acuerdos internacionales.

Savoir détecter l'exposition des enfants à la violence entre partenaires intimes, qu'elle soit présumée ou divulguée, et savoir intervenir.

L'exposition des enfants à la violence entre partenaires intimes (EEVPI), qu'il s'agisse des parents ou d'autres proches, représente près de la moitié de tous les cas qui font l'objet d'une enquête et sont corroborés par les services de protection de l'enfance du Canada. Les atteintes affectives, physiques et comportementales associées à l'EEVPI sont semblables aux effets d'autres formes de maltraitance envers les enfants. Il peut être difficile d'établir quels enfants et adolescents sont exposés à la violence entre partenaires intimes (VPI) en raison des comportements non spécifiques parfois associés à une telle exposition, de même que de la stigmatisation et du secret entourant souvent ce type de violence. Par ailleurs, une intervention en toute sécurité auprès des enfants et des adolescents chez qui on présume une exposition à la VPI peut être compliquée par la nécessité d'également tenir compte de la sécurité et du bien-être d'un proche non contrevenant. Le présent document de principes propose une approche fondée sur des données probantes mise au point par le projet VEGA (Violence, Evidence, Guidance, Action ou violence, données probantes, conseils, action) pour détecter l'exposition des enfants et des adolescents à la VPI et intervenir en toute sécurité auprès d'eux.

Recognizing and responding to children with suspected exposure to intimate partner violence between caregivers.

Children's exposure to intimate partner violence (CEIPV) between parents and other caregivers accounts for nearly half of all cases investigated and substantiated by child welfare authorities in Canada. The emotional, physical, and behavioural impairments associated with CEIPV are similar to effects of other forms of child maltreatment. The identification of children and youth who have been exposed to intimate partner violence (IPV) can be challenging due to the non-specific behaviours sometimes associated with such exposure, and the stigma and secrecy that often characterize IPV. Also, responding safely to children and youth with suspected CEIPV can be complicated by the need to consider the safety and well-being of a non-offending caregiver. This position statement presents an evidence-informed approach developed by the Violence, Evidence, Guidance, Action (VEGA) Project for the safe recognition and response to children and youth who are suspected of being exposed to IPV.

Acceptability and feasibility of screening with a pediatric care provider-led social determinants of health identification tool.

BACKGROUND: Complex social determinants of health may not be easily recognized by health care providers and pose a unique challenge in the vulnerable pediatric population where patients may not be able to advocate for themselves. The goal of this study was to examine the acceptability and feasibility of health care providers using an integrated brief pediatric screening tool in primary care and hospital settings. METHODS: The framework of the Child and Adolescent Needs and Strengths (CANS) and Pediatric Intermed tools was used to inform the selection of items for the 9-item Child and Adolescent Needs and Strengths-Pediatric Complexity Indicator (CANS-PCI). The tool consisted of three domains: biological, psychological, and social. Semi-structured interviews were conducted with health care providers in pediatric medical facilities in Ottawa, Canada. A low inference and iterative thematic synthesis approach was used to analyze the qualitative interview data specific to acceptability and feasibility. RESULTS: Thirteen health care providers participated in interviews. Six overarching themes were identified: acceptability, logistics, feasibility, pros/cons, risk, and privacy. Overall, participants agreed that a routine, trained provider-led pediatric tool for the screening of social determinants of health is important (n = 10, 76.9%), acceptable (n = 11; 84.6%), and feasible (n = 7, 53.8%). INTERPRETATION: Though the importance of social determinants of health are widely recognized, there are limited systematic methods of assessing, describing, and communicating amongst health care providers about the biomedical and psychosocial complexities of pediatric patients. Based on this study's findings, implementation of a brief provider-led screening tool into pediatric care practices may contribute to this gap.

Niche-based approach to explore the impacts of environmental disturbances on biodiversity.

Globally, species are increasingly at risk from compounding threatening processes, an increasingly prominent driver of which is environmental disturbances. To facilitate effective conservation efforts following such events, methods that evaluate potential impacts across multiple species and provide landscape-scale information are needed to guide targeted responses. Often, the geographic overlap between a disturbance and species' distribution is calculated and then used as a proxy for potential impact. However, such methods do not account for the important influence of environmental heterogeneity throughout species' ranges. To address this shortcoming, we quantified the effects of environmental disturbances on species' environmental niche space. Using the Australian 2019 and 2020 Black Summer fires as a case study, we applied a niche-centric approach to examine the potential impacts of these fires on 387 vertebrate species. We examined the utility of established and novel niche metrics to assess the potential impacts of large-scale disturbance events on species by comparing the potential effects of the fires as determined by our various niche measures to those derived from geographic-based measures of impact. We examined the quality of environmental space affected by the disturbance by quantifying the position in niche space where the disturbance occurred (center or margin), the uniqueness of the environmental space that was burned, and the degree to which the remaining, unburned portion of the niche differed from a species' original prefire niche. There was limited congruence between the proportion of geographic and niche space affected, which showed that geographic-based approaches in isolation may have underestimated the impact of the fires for 56% of modeled species. For each species, when combined, these metrics provided a greater indication of postdisturbance recovery potential than geographic-based measures alone. Accordingly, the integration of niche-based analyses into conservation assessments following large-scale disturbance events will lead to a more nuanced understanding of potential impacts and guide more informed and effective conservation actions.

Estrategia basada en los nichos para explorar el impacto de la perturbación ambiental sobre la biodiversidad Resumen En todo el mundo, las especies corren un riesgo cada vez mayor de verse amenazadas por procesos combinados, entre los que destacan las perturbaciones ambientales. Para facilitar una labor de conservación eficaz después de estos fenómenos, se necesitan métodos que evalúen el impacto potencial en varias especies y proporcionen información a escala de paisaje para orientar las respuestas específicas. A menudo, se calcula el traslape geográfico entre una perturbación y la distribución de las especies y se utiliza como indicador del impacto potencial. Sin embargo, estos métodos no tienen en cuenta la influencia importante de la heterogeneidad ambiental en toda el área de distribución de las especies. Para abordar esta deficiencia, cuantificamos los efectos de las perturbaciones ambientales en el espacio del nicho ambiental de las especies. Usamos los incendios australianos de Black Summer de 2019 y 2020 como caso de estudio y aplicamos un enfoque centrado en el nicho para examinar los impactos potenciales de estos incendios en 387 especies de vertebrados. Analizamos la utilidad de las métricas nuevas y establecidas de nicho para evaluar los impactos potenciales de los eventos de perturbación a gran escala para las especies con la comparación de los efectos potenciales de los incendios determinados por nuestras diversas medidas de nicho con los derivados de las medidas de impacto basadas en la geografía. Examinamos la calidad del espacio ambiental afectado por la perturbación al cuantificar la posición en el espacio del nicho donde se produjo la perturbación (centro o margen), la singularidad del espacio ambiental que se quemó y el grado en que la parte restante no quemada del nicho difería del nicho original de una especie antes del incendio. Hubo una congruencia limitada entre la proporción del espacio geográfico y del nicho afectado, lo que demostró que los enfoques geográficos aislados pueden subestimar el impacto de los incendios para el 56% de las especies modeladas. Para cada especie, estas métricas combinadas proporcionaron una mayor indicación del potencial de recuperación tras las perturbaciones que las medidas geográficas por sí solas. Por lo tanto, la integración de los análisis basados en nichos en las evaluaciones de conservación tras perturbaciones a gran escala permitirá comprender mejor los impactos potenciales y orientar las acciones de conservación de manera más informada y eficaz.

Youth, caregiver and healthcare professional perspectives on planning the implementation of a trauma-informed care programme: A qualitative study.

AIMS: To explore youth, caregiver and staff perspectives on their vision of trauma-informed care, and to identify and understand potential considerations for the implementation of a trauma-informed care programme in an inpatient mental health unit within a paediatric hospital. DESIGN AND METHODS: We applied the Interpretive Description approach, guided by complexity theory and the Implementation Roadmap, and used Applied Thematic Analysis methods. FINDINGS: Twenty-five individuals participated in individual or group interviews between March and June 2022, including 21 healthcare professionals, 3 youth and 1 caregiver. We identified two overarching themes. The first theme, 'Understanding and addressing the underlying reasons for distress', related to participants' understanding and vision of TIC in the current setting comprising: (a) 'Participants' understanding of TIC'; (b) 'Trauma screening and trauma processing within TIC'; (c) 'Taking "a more individualized approach"'; (d) 'Unit programming'; and (e) "Connecting to the community". The second theme, 'Factors that support or limit successful TIC implementation' comprises: (a) 'The need for a broad "cultural shift"'; (b) 'The physical environment on the unit'; and (c) 'Factors that may limit successful implementation'. CONCLUSION: We identified five key domains to consider within trauma-informed care implementation: (a) the centrality of engagement with youth, caregivers and staff in trauma-informed care delivery and implementation, (b) trauma-informed care core programme components, (c) factors that may support or limit success in implementing trauma-informed care within the mental health unit and (d) hospital-wide and (e) the importance of intersectoral collaboration (partnering with external organizations and sectors). IMPACT: When implementing TIC, there is an ongoing need to increase clarity regarding TIC interventions and implementation initiatives. Youth, caregiver and healthcare professional participants shared considerations important for planning the delivery and implementation of trauma-informed care in their setting. We identified five key domains to consider within trauma-informed care implementation: (a) the centrality of relational engagement, (b) trauma-informed care programme components, (c) factors that may support or limit successful implementation of trauma-informed care within the mental health unit and (d) hospital-wide and (e) the importance of intersectoral collaboration. Organizations wishing to implement trauma-informed care should consider ongoing engagement with all relevant knowledge user groups throughout the process. REPORTING METHOD: Standards for Reporting Qualitative Research (SRQR). PATIENT OR PUBLIC CONTRIBUTION: The local hospital research institute's Patient and Family Advisory Committee reviewed the draft study methods and provided feedback.

Identifying child maltreatment during virtual medical appointments through the COVID-19 pandemic: A physician-based survey.

Background: Throughout the COVID-19 pandemic there has been a documented decline in reports to child protective services, despite an increased incidence of child maltreatment. This is concerning for increasing missed cases. This study aims to examine if and how Canadian paediatricians are identifying maltreatment in virtual medical appointments. Methods: A survey was sent through the Canadian Paediatric Surveillance Program (CPSP) to 2770 practicing general and subspecialty paediatricians. Data was collected November 2021 to January 2022. Results: With a 34% (928/2770) response rate, 704 surveys were eligible for analysis. At least one case of child maltreatment was reported by 11% (78/700) of respondents following a virtual appointment. The number of cases reported was associated with years in medical practice (P = 0.026) but not with the volume (P = 0.735) or prior experience (P = 0.127) with virtual care, or perceived difficulty in identifying cases virtually (Cramer's V = 0.096). The most common factors triggering concern were the presence of social stressors, or a clear disclosure. The virtual physical exam was not contributory. Nearly one quarter (24%, 34/143) required a subsequent in-person appointment prior to reporting the case and 32% (207/648) reported concerns that a case had been identified late, or missed, following a virtual appointment. Some commented that clear harm resulted. Conclusions: Many barriers to detecting child maltreatment were identified by paediatricians who used virtual care. This survey reveals that virtual care may be an important factor in missed cases of child maltreatment and may present challenges to timely identification.

Anthracyclines induce cardiotoxicity through a shared gene expression response signature.

TOP2 inhibitors (TOP2i) are effective drugs for breast cancer treatment. However, they can cause cardiotoxicity in some women. The most widely used TOP2i include anthracyclines (AC) Doxorubicin (DOX), Daunorubicin (DNR), Epirubicin (EPI), and the anthraquinone Mitoxantrone (MTX). It is unclear whether women would experience the same adverse effects from all drugs in this class, or if specific drugs would be preferable for certain individuals based on their cardiotoxicity risk profile. To investigate this, we studied the effects of treatment of DOX, DNR, EPI, MTX, and an unrelated monoclonal antibody Trastuzumab (TRZ) on iPSC-derived cardiomyocytes (iPSC-CMs) from six healthy females. All TOP2i induce cell death at concentrations observed in cancer patient serum, while TRZ does not. A sub-lethal dose of all TOP2i induces limited cellular stress but affects calcium handling, a function critical for cardiomyocyte contraction. TOP2i induce thousands of gene expression changes over time, giving rise to four distinct gene expression response signatures, denoted as TOP2i early-acute, early-sustained, and late response genes, and non-response genes. There is no drug- or AC-specific signature. TOP2i early response genes are enriched in chromatin regulators, which mediate AC sensitivity across breast cancer patients. However, there is increased transcriptional variability between individuals following AC treatments. To investigate potential genetic effects on response variability, we first identified a reported set of expression quantitative trait loci (eQTLs) uncovered following DOX treatment in iPSC-CMs. Indeed, DOX response eQTLs are enriched in genes that respond to all TOP2i. Next, we identified 38 genes in loci associated with AC toxicity by GWAS or TWAS. Two thirds of the genes that respond to at least one TOP2i, respond to all ACs with the same direction of effect. Our data demonstrate that TOP2i induce thousands of shared gene expression changes in cardiomyocytes, including genes near SNPs associated with inter-individual variation in response to DOX treatment and AC-induced cardiotoxicity.

Successful aging after elective surgery II: Study cohort description.

BACKGROUND: The Successful Aging after Elective Surgery (SAGES) II Study was designed to examine the relationship between delirium and Alzheimer's disease and related dementias (AD/ADRD), by capturing novel fluid biomarkers, neuroimaging markers, and neurophysiological measurements. The goal of this paper is to provide the first complete description of the enrolled cohort, which details the baseline characteristics and data completion. We also describe the study modifications necessitated by the COVID-19 pandemic, and lay the foundation for future work using this cohort. METHODS: SAGES II is a prospective observational cohort study of community-dwelling adults age 65 and older undergoing major non-cardiac surgery. Participants were assessed preoperatively, throughout hospitalization, and at 1, 2, 6, 12, and 18 months following discharge to assess cognitive and physical functioning. Since participants were enrolled throughout the COVID-19 pandemic, procedural modifications were designed to reduce missing data and allow for high data quality. RESULTS: About 420 participants were enrolled with a mean (standard deviation) age of 73.4 (5.6) years, including 14% minority participants. Eighty-eight percent of participants had either total knee or hip replacements; the most common surgery was total knee replacement with 210 participants (50%). Despite the challenges posed by the COVID-19 pandemic, which required the use of novel procedures such as video assessments, there were minimal missing interviews during hospitalization and up to 1-month follow-up; nearly 90% of enrolled participants completed interviews through 6-month follow-up. CONCLUSION: While there are many longitudinal studies of older adults, this study is unique in measuring health outcomes following surgery, along with risk factors for delirium through the application of novel biomarkers-including fluid (plasma and cerebrospinal fluid), imaging, and electrophysiological markers. This paper is the first to describe the characteristics of this unique cohort and the data collected, enabling future work using this novel and important resource.

CRISPR-Cas9-generated PTCHD1 2489T>G stem cells recapitulate patient phenotype when undergoing neural induction.

An estimated 3.5%-5.9% of the global population live with rare diseases, and approximately 80% of these diseases have a genetic cause. Rare genetic diseases are difficult to diagnose, with some affected individuals experiencing diagnostic delays of 5-30 years. Next-generation sequencing has improved clinical diagnostic rates to 33%-48%. In a majority of cases, novel variants potentially causing the disease are discovered. These variants require functional validation in specialist laboratories, resulting in a diagnostic delay. In the interim, the finding is classified as a genetic variant of uncertain significance (VUS) and the affected individual remains undiagnosed. A VUS (PTCHD1 c. 2489T>G) was identified in a child with autistic behavior, global developmental delay, and hypotonia. Loss of function mutations in PTCHD1 are associated with autism spectrum disorder and intellectual disability; however, the molecular function of PTCHD1 and its role in neurodevelopmental disease is unknown. Here, we apply CRISPR gene editing and induced pluripotent stem cell (iPSC) neural disease modeling to assess the variant. During differentiation from iPSCs to neural progenitors, we detect subtle but significant gene signatures in synaptic transmission and muscle contraction pathways. Our work supports the causal link between the genetic variant and the child's phenotype, providing evidence for the variant to be considered a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. In addition, our study provides molecular data on the role of PTCHD1 in the context of other neurodevelopmental disorders.

Gene editing and cardiac disease modelling for the interpretation of genetic variants of uncertain significance in congenital heart disease.

BACKGROUND: Genomic sequencing in congenital heart disease (CHD) patients often discovers novel genetic variants, which are classified as variants of uncertain significance (VUS). Functional analysis of each VUS is required in specialised laboratories, to determine whether the VUS is disease causative or not, leading to lengthy diagnostic delays. We investigated stem cell cardiac disease modelling and transcriptomics for the purpose of genetic variant classification using a GATA4 (p.Arg283Cys) VUS in a patient with CHD. METHODS: We performed high efficiency CRISPR gene editing with homology directed repair in induced pluripotent stem cells (iPSCs), followed by rapid clonal selection with amplicon sequencing. Genetic variant and healthy matched control cells were compared using cardiomyocyte disease modelling and transcriptomics. RESULTS: Genetic variant and healthy cardiomyocytes similarly expressed Troponin T (cTNNT), and GATA4. Transcriptomics analysis of cardiomyocyte differentiation identified changes consistent with the patient's clinical human phenotype ontology terms. Further, transcriptomics revealed changes in calcium signalling, and cardiomyocyte adrenergic signalling in the variant cells. Functional testing demonstrated, altered action potentials in GATA4 genetic variant cardiomyocytes were consistent with patient cardiac abnormalities. CONCLUSIONS: This work provides in vivo functional studies supportive of a damaging effect on the gene or gene product. Furthermore, we demonstrate the utility of iPSCs, CRISPR gene editing and cardiac disease modelling for genetic variant interpretation. The method can readily be applied to other genetic variants in GATA4 or other genes in cardiac disease, providing a centralised assessment pathway for patient genetic variant interpretation.

Quality-of-Life Assessments in Zoo Animals: Not Just for the Aged and Charismatic.

Zoos should aim to provide all of their animals with a good quality of life (QoL) throughout all life stages. In parallel with the evolution of QoL assessment questionnaires and tools in human and domestic animal settings, in recent times, some individual zoos and zoo industry associations have incorporated such instruments into their animal management practices. This has been conducted predominantly to inform, monitor, and document end-of-life decision-making for large, charismatic mammals. There is scope to expand the use of these tools to improve their utility, validity, reliability, and value to an animal welfare program. Assessment of QoL is a complex task given that the notion being measured is abstract and self-determined, and the design and purpose of the tools to do this require careful consideration. This review explores the QoL concept as it applies to animals, the assessment indications and methodologies relevant to a zoo setting, and the importance of considering QoL at any life stage across species. An overview of current thinking and the applications and limitations of QoL evaluation of captive wild animals is offered to promote and aid facility practice reviews and to help direct future innovations that leverage concurrent and converging advances in zoo animal welfare science.

Trauma-Informed Care Interventions Used in Pediatric Inpatient or Residential Treatment Mental Health Settings and Strategies to Implement Them: A Scoping Review.

Trauma-informed care (TIC) is an approach to care emerging in research and in practice that involves addressing the needs of individuals with histories of trauma. The aim of this scoping review was to examine the current literature relating to TIC interventions used in pediatric mental health inpatient and residential settings. We sought to answer the following two research questions: (a) What are the TIC interventions used in pediatric inpatient and residential treatment mental healthcare settings and what are their components? and (b) What are the implementation goals and strategies used with these TIC interventions? We conducted this scoping review according to JBI (formerly Joanna Briggs Institute) methodology for scoping reviews. We included any primary study describing a TIC intervention that was implemented at a specific site which identified and described implementation strategies used. Of 1,571 identified citations and 54 full-text articles located by handsearching, 49 met the eligibility criteria and were included, representing 21 distinct TIC interventions. We present the reported aim, ingredients, mechanism, and delivery (AIMD) of TIC interventions as well as the implementation goals and strategies used, which varied in detail, ranging from very little information to more detailed descriptions. In the context of these findings, we emphasize the complexity of TIC and of TIC interventions, and the importance of identifying and clearly reporting TIC intervention goals, intervention details, and implementation strategies. We suggest applying intervention frameworks or reporting guidelines to support clear and comprehensive reporting, which would better facilitate replication and synthesis of published TIC interventions.

Integrated multi-omics for rapid rare disease diagnosis on a national scale.

Critically ill infants and children with rare diseases need equitable access to rapid and accurate diagnosis to direct clinical management. Over 2 years, the Acute Care Genomics program provided whole-genome sequencing to 290 families whose critically ill infants and children were admitted to hospitals throughout Australia with suspected genetic conditions. The average time to result was 2.9 d and diagnostic yield was 47%. We performed additional bioinformatic analyses and transcriptome sequencing in all patients who remained undiagnosed. Long-read sequencing and functional assays, ranging from clinically accredited enzyme analysis to bespoke quantitative proteomics, were deployed in selected cases. This resulted in an additional 19 diagnoses and an overall diagnostic yield of 54%. Diagnostic variants ranged from structural chromosomal abnormalities through to an intronic retrotransposon, disrupting splicing. Critical care management changed in 120 diagnosed patients (77%). This included major impacts, such as informing precision treatments, surgical and transplant decisions and palliation, in 94 patients (60%). Our results provide preliminary evidence of the clinical utility of integrating multi-omic approaches into mainstream diagnostic practice to fully realize the potential of rare disease genomic testing in a timely manner.

Evaluating the impact of biodiversity offsetting on native vegetation.

Biodiversity offsetting is a globally influential policy mechanism for reconciling trade-offs between development and biodiversity loss. However, there is little robust evidence of its effectiveness. We evaluated the outcomes of a jurisdictional offsetting policy (Victoria, Australia). Offsets under Victoria's Native Vegetation Framework (2002-2013) aimed to prevent loss and degradation of remnant vegetation, and generate gains in vegetation extent and quality. We categorised offsets into those with near-complete baseline woody vegetation cover ("avoided loss", 2702 ha) and with incomplete cover ("regeneration", 501 ha), and evaluated impacts on woody vegetation extent from 2008 to 2018. We used two approaches to estimate the counterfactual. First, we used statistical matching on biophysical covariates: a common approach in conservation impact evaluation, but which risks ignoring potentially important psychosocial confounders. Second, we compared changes in offsets with changes in sites that were not offsets for the study duration but were later enrolled as offsets, to partially account for self-selection bias (where landholders enrolling land may have shared characteristics affecting how they manage land). Matching on biophysical covariates, we estimated that regeneration offsets increased woody vegetation extent by 1.9%-3.6%/year more than non-offset sites (138-180 ha from 2008 to 2018) but this effect weakened with the second approach (0.3%-1.9%/year more than non-offset sites; 19-97 ha from 2008 to 2018) and disappeared when a single outlier land parcel was removed. Neither approach detected any impact of avoided loss offsets. We cannot conclusively demonstrate whether the policy goal of 'net gain' (NG) was achieved because of data limitations. However, given our evidence that the majority of increases in woody vegetation extent were not additional (would have happened without the scheme), a NG outcome seems unlikely. The results highlight the importance of considering self-selection bias in the design and evaluation of regulatory biodiversity offsetting policy, and the challenges of conducting robust impact evaluations of jurisdictional biodiversity offsetting policies.

Feasibility and performance of home sleep apnea testing in youth with Down syndrome.

STUDY OBJECTIVES: In-laboratory polysomnography is recommended for the evaluation of obstructive sleep apnea (OSA) in youth with Down syndrome. However, insufficient sleep laboratories are available, particularly for youth with neurocognitive disabilities such as Down syndrome. We hypothesized that level II home sleep apnea testing (HSAT) would be feasible, acceptable, and accurate in detecting polysomnography-defined moderate-severe OSA in youth with Down syndrome. METHODS: Youth 6 to 25 years old with Down syndrome were recruited to undergo in-home level II HSAT with electroencephalogram and in-lab polysomnography. Parents completed questionnaires assessing feasibility, acceptability, and test preference. HSAT, scored blinded to polysomnography result, were compared to reference polysomnography. RESULTS: Forty-three youth (23 female) aged [median (range)] 15.5 (6.1, 25.1) years participated in the study. Forty-one participants were able to complete HSAT and 41 completed polysomnography, with 40 who underwent both tests. HSAT was preferred to polysomnography by 73.7% of parents. Total sleep time for HSAT was 437 ± 123 minutes vs 366 ± 90 minutes for polysomnography (P = .003). Obstructive apnea-hypopnea index by polysomnography was 12.7 events/h (0.2, 113.8), and 32 youth (80%) who completed all testing had OSA. Compared to polysomnography, sensitivity of HSAT was: 0.81, specificity was 0.75, accuracy was 0.8 including 2 youth whose HSAT demonstrated OSA when polysomnography did not. CONCLUSIONS: In youth with Down syndrome, level II HSAT was well-tolerated, preferred compared to in-lab polysomnography, and had good accuracy for detecting moderate-severe OSA. Level II HSAT could provide a means for expanding the evaluation of OSA in youth with Down syndrome. CITATION: Cielo CM, Kelly A, Xanthopoulos M, et al. Feasibility and performance of home sleep apnea testing in youth with Down syndrome J Clin Sleep Med. 2023;19(9):1605-1613.