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Introduction: Chediak-Higashi syndrome (CHS) is rare autosomal recessive disorder caused by bi-allelic variants in the Lysosomal Trafficking Regulator (LYST) gene. Diagnosis is established by the detection of pathogenic variants in LYST in combination with clinical evidence of disease. Conventional molecular genetic testing of LYST by genomic DNA (gDNA) Sanger sequencing detects the majority of pathogenic variants, but some remain undetected for several individuals clinically diagnosed with CHS. In this study, cDNA Sanger sequencing was pursued as a complementary method to identify variant alleles that are undetected by gDNA Sanger sequencing and to increase molecular diagnostic yield.Methods: Six unrelated individuals with CHS were clinically evaluated and included in this study. gDNA Sanger sequencing and cDNA Sanger sequencing were performed to identify pathogenic LYST variants.Results: Ten novel LYST alleles were identified, including eight nonsense or frameshift variants and two in-frame deletions. Six of these were identified by conventional gDNA Sanger sequencing; cDNA Sanger sequencing was required to identify the remaining variant alleles.Conclusion: By utilizing cDNA sequencing as a complementary technique to identify LYST variants, a complete molecular diagnosis was obtained for all six CHS patients. In this small CHS cohort, the molecular diagnostic yield was increased, and canonical splice site variants identified from gDNA Sanger sequencing were validated by cDNA sequencing. The identification of novel LYST alleles will aid in diagnosing patients and these molecular diagnoses will also lead to genetic counseling, access to services and treatments and clinical trials in the future.

Streamflow regimes that maintain vital functions and processes of aquatic ecosystems are critical to sustaining ecosystem health. In rivers with altered flow regimes, restoring components of the natural flow regime is predicted to conserve freshwater biodiversity by supporting ecological functions and geomorphological processes to which native communities are adapted. However, the effectiveness of environmental flow restoration is poorly understood because of inadequate monitoring and uncertainty in ecological responses to managed changes in specific, quantifiable aspects of the annual streamflow regime. Here, we used time series models to analyze 25 years of fish assemblage data collected before and after environmental flow implementation in a dammed river in California, USA. We examined the response of the fish community to changes in individual components of the flow regime known to support ecosystem functions. We found that as functional flow components shifted toward their predicted natural range, the quasi‐extinction risk (likelihood of population declines of >80%) decreased for the native fish assemblage. Following environmental flow implementation, observed changes toward natural ranges of dry season duration, fall pulse flow magnitude, and wet season timing each reduced quasi‐extinction risk by at least 40% for the native assemblage. However, functional flow components that shifted away from their predicted natural range, including lower spring recession flows and higher dry season baseflow, resulted in greater quasi‐extinction risk for native species. In contrast, non‐native species decreased in abundance when flow components shifted toward predicted natural ranges and increased when components shifted away from their natural range. Although most functional flow components remained outside of their natural range following environmental flow implementation, our results indicate that even moderate shifts toward a natural flow regime can benefit native and suppress non‐native fish species. Overall, this study provides the most compelling evidence to date of the effectiveness of functional environmental flows in supporting native fish recovery in a highly regulated river. [ABSTRACT FROM AUTHOR]

Environmental flows (e-flows) aim to mitigate the threat of altered hydrological regimes in river systems and connected waterbodies and are an important component of integrated strategies to address multiple threats to freshwater biodiversity. Expanding and accelerating implementation of e-flows can support river conservation and help to restore the biodiversity and resilience of hydrologically altered and water-stressed rivers and connected freshwater ecosystems. While there have been significant developments in e-flow science, assessment, and societal acceptance, implementation of e-flows within water resource management has been slower than required and geographically uneven. This review explores critical factors that enable successful e-flow implementation and biodiversity outcomes in particular, drawing on 13 case studies and the literature. It presents e-flow implementation as an adaptive management cycle enabled by 10 factors: legislation and governance, financial and human resourcing, stakeholder engagement and co-production of knowledge, collaborative monitoring of ecological and social-economic outcomes, capacity training and research, exploration of trade-offs among water users, removing or retrofitting water infrastructure to facilitate e-flows and connectivity, and adaptation to climate change. Recognising that there may be barriers and limitations to the full and effective enablement of each factor, the authors have identified corresponding options and generalizable recommendations for actions to overcome prominent constraints, drawing on the case studies and wider literature. The urgency of addressing flow-related freshwater biodiversity loss demands collaborative networks to train and empower a new generation of e-flow practitioners equipped with the latest tools and insights to lead adaptive environmental water management globally. Mainstreaming e-flows within conservation planning, integrated water resource management, river restoration strategies, and adaptations to climate change is imperative. The policy drivers and associated funding commitments of the Kunming–Montreal Global Biodiversity Framework offer crucial opportunities to achieve the human benefits contributed by e-flows as nature-based solutions, such as flood risk management, floodplain fisheries restoration, and increased river resilience to climate change. [ABSTRACT FROM AUTHOR]

Balancing ecological and human water needs often requires characterizing key aspects of the natural flow regime and then predicting ecological response to flow alterations. Flow metrics are generally relied upon to characterize long-term average statistical properties of the natural flow regime (hydrologic baseline conditions). However, some key aspects of hydrologic baseline conditions may be better understood through more complete consideration of continuous patterns of daily, seasonal, and inter-annual variability than through summary metrics. Here we propose the additional use of high-resolution dimensionless archetypes of regional stream classes to improve understanding of baseline hydrologic conditions and inform regional environmental flows assessments. In an application to California, we describe the development and analysis of hydrologic baseline archetypes to characterize patterns of flow variability within and between stream classes. We then assess the utility of archetypes to provide context for common flow metrics and improve understanding of linkages between aquatic patterns and processes and their hydrologic controls. Results indicate that these archetypes may offer a distinct and complementary tool for researching mechanistic flow-ecology relationships, assessing regional patterns for streamflow management, or understanding impacts of changing climate.

Abstract The consequences of poor breed management and inbreeding can range from gradual declines in individual productivity to more serious fertility and mortality concerns. However, many small and closed groups, as well as larger unmanaged populations, are plagued by genetic regression, often due to a dearth in breeding support tools which are accessible and easy to use in supporting decision‐making. To address this, we have developed a population management tool (BCAS, Breed Conservation and Management System) based on individual relatedness assessed using pedigree‐based kinship, which offers breeding recommendations for such populations. Moreover, we demonstrate the success of this tool in 16 years of employment in a closed equine population native to the UK, most notably, the rate of inbreeding reducing from more than 3% per generation, to less than 0.5%, or that attributed to genetic drift, as assessed over the last 16 years of implementation. Furthermore, with adherence to this program, the long‐term impact of poor management has been reversed and the genetic resource within the breed has grown from an effective population size of 20 in 1994 to more than 140 in 2020. The development and availability of our BCAS for breed management and selection establish a new paradigm for the successful maintenance of genetic resources in animal populations.

Abstract Background Recently immigrated and ethnic minority patients in Ontario, Canada are more likely to receive aggressive life-prolonging treatment at the end of life in comparison to other patients. To explore this finding further, this survey-based observational study aimed to evaluate satisfaction with the quality of end-of-life care for patients from diverse ethnocultural backgrounds. Methods The End-of-Life Satisfaction Survey was used to measure satisfaction with the quality of inpatient end-of-life care from the perspective of next-of-kin of recently deceased patients at Sunnybrook Health Sciences Centre in Toronto, Ontario (between March 2012 to May 2019). The primary outcome was the global rating of satisfaction. Associations with patient ethnicity, patient religion, level of religiosity/spirituality, language/communication barriers, and location of death were assessed using univariable and multivariable modified Poisson regression. Secondary outcomes included differences in satisfaction and rates of dying in intensive care units (ICU) among patient population subgroups, and identification of high priority areas for quality-of-care improvement. Results There were 1,543 respondents. Patient ethnicities included Caucasian (68.2%), Mediterranean (10.5%), East Asian (7.6%), South Asian (3.5%), Southeast Asian (2.1%) and Middle Eastern (2.0%); religious affiliations included Christianity (66.6%), Judaism (12.3%) and Islam (2.1%), among others. Location of death was most commonly in ICU (38.4%), hospital wards (37.0%) or long-term care (20.0%). The mean(SD) rating of satisfaction score was 8.30(2.09) of 10. After adjusting for other covariates, satisfaction with quality of end-of-life care was higher among patients dying in ICU versus other locations (relative risk [RR] 1.51, 95%CI 1.05-2.19, p=0.028), lower among those who experienced language/communication barriers (RR 0.49 95%CI 0.23-1.06, p=0.069), and lower for Muslim patients versus other religious affiliations (RR 0.46, 95%CI 0.21-1.02, p=0.056). Survey items identified as highest priority areas for quality-of-care improvement included communication and information giving; illness management; and healthcare provider characteristics such as emotional support, doctor availability and time spent with patient/family. Conclusion Satisfaction with quality-of-care at the end of life was higher among patients dying in ICU and lower among Muslim patients or when there were communication barriers between families and healthcare providers. These findings highlight the importance of measuring and improving end-of-life care across the ethnocultural spectrum.

Abstract Military and law enforcement breachers are exposed to many low-level blasts during their training and occupational experiences in which they detonate explosives to force entry into secured structures. There is a concern that exposure to these repetitive blast events in career breachers could result in cumulative neurological effects. This study aimed to determine concentrations of neurofilament light (NF-L), tau, and amyloid-beta 42 (Aβ42) in serum and in neuronal-derived extracellular vesicles (EVs) in an experienced breacher population, and to examine biomarker associations with neurobehavioral symptoms. Thirty-four participants enrolled in the study: 20 experienced breachers and 14 matched military or civilian law enforcement controls. EV tau concentrations were significantly elevated in experienced breachers (0.3301 ± 0.5225) compared to controls (−0.4279 ± 0.7557; F = 10.43, p = 0.003). No statistically significant changes were observed in EV levels of NF-L or Aβ42 or in serum levels of NF-L, tau, or Aβ42 (p’s > 0.05). Elevated EV tau concentrations correlated with increased Neurobehavioral Symptom Inventory (NSI) score in experienced breachers (r = 0.596, p = 0.015) and predicted higher NSI score (F(1,14) = 7.702, p = 0.015, R 2 = 0.355). These findings show that neuronal-derived EV concentrations of tau are significantly elevated and associated with neurobehavioral symptoms in this sample of experienced breachers who have a history of many low-level blast exposures.

While water resource managers and river scientists recognize the inherent interconnections among hydrology, river structure, biophysical processes and ecological patterns, management of environmental flows still pays insufficient attention to the ecological and geomorphological functionality of particular aspects of the flow regime. Implementation of more natural flow regimes has improved habitat conditions for native species in many moderately impaired rivers but mimicking a natural flow regime in heavily modified riverine landscapes cannot be expected to yield successful ecological outcomes unless such flows trigger functional processes. For example, the restoration of peak flows may not regenerate habitats if the river is starved of sediment or if the river channel is highly confined. High biodiversity is supported when variable flow regimes interact with spatially variable (heterogeneous) river channel and floodplain forms. In contrast, as rivers become homogeneous, biodiversity decreases when these dynamic spatiotemporal interactions are limited by flow alterations, blocked by channel levees, or perturbed by sediment deficit or surplus. Thus, the design of a more natural environmental flow regime without consideration of the implications for sediment transport and implicit recognition of channel–floodplain geomorphology is likely to have limited success in river management and restoration. To enhance the functionality of environmental flows, considerations of physical, biogeochemical, and ecological processes and the inherent heterogeneity of the riverine landscape must be included. A Functional Flows approach enhances the benefits from limited environmental flow allocations by focusing on the ecological and geomorphological functionality of particular aspects of the flow regime, considering geomorphic context, and emphasizing spatiotemporal diversity at key locations in the riverscape, such as adjacent floodplains or tributary junctions. In this paper, we outline and illustrate the concept of Functional Flows using a flow-chain model and provide two case study examples from Australia and the United States, where improvements in channel habitat and reconnection with the floodplain help to achieve the desired functionality of environmental flows.

Abstract Effective conservation management requires an understanding of the spatiotemporal dynamics driving large carnivore density and resource partitioning. In African ecosystems, reduced prey populations and the loss of competing guild members, most notably lion (Panthera leo), are expected to increase the levels of competition between remaining carnivores. Consequently, intraguild relationships can be altered, potentially increasing the risk of further population decline. Kasungu National Park (KNP), Malawi, is an example of a conservation area that has experienced large‐scale reductions in both carnivore and prey populations, leaving a resident large carnivore guild consisting of only leopard (Panthera pardus) and spotted hyena (Crocuta crocuta). Here, we quantify the spatiotemporal dynamics of these two species and their degree of association, using a combination of co‐detection modeling, time‐to‐event analyses, and temporal activity patterns from camera trap data. The detection of leopard and spotted hyena was significantly associated with the detection of preferred prey and competing carnivores, increasing the likelihood of species interaction. Temporal analyses revealed sex‐specific differences in temporal activity, with female leopard activity patterns significantly different to those of spotted hyena and male conspecifics. Heightened risk of interaction with interspecific competitors and male conspecifics may have resulted in female leopards adopting temporal avoidance strategies to facilitate coexistence. Female leopard behavioral adaptations increased overall activity levels and diurnal activity rates, with potential consequences for overall fitness and exposure to sources of mortality. As both species are currently found at low densities in KNP, increased risk of competitive interactions, which infer a reduction in fitness, could have significant implications for large carnivore demographics. The protection of remaining prey populations is necessary to mitigate interspecific competition and avoid further alterations to the large carnivore guild.

Environmental flow management in watersheds with multi-objective reservoirs is often presented as an additional constraint to an already strained and over-allocated stream system. Nevertheless, environmental flow legislation and regulatory policies are increasingly being developed and implemented globally. In California, USA, recent legislative and regulatory policies place environmental flows at the forefront of the state’s water management objectives; however, the increased reliance on hydropower to support climate change mitigation goals may complicate efforts on both issues. This study modelled alternative environmental flow strategies in the major tributaries to the San Joaquin River in California. Strategies included detailed water management rules for hydropower production, flood control, and water deliveries, and three methodological approaches to environmental flow releases: minimum instream flows (“baseline”) year-round, 40% of full natural flow (FNF) during the spring runoff season and minimum releases the remainder of the year, and functional flows year-round. Results show that environmental flow strategies affect downstream flow releases in each of the San Joaquin’s four sub-basins differently depending on infrastructure capacity, water management objectives, and hydrologic year types. While hydropower production was comparable or declined in the Stanislaus, Tuolumne, and Merced basins, functional flow and 40% FNF strategies increased hydropower production in the Upper San Joaquin basin by 11%. Uncontrolled spill of high flow events decreased when high flow releases were based on hydrologic cues rather than exclusively on flood storage capacity. Water deliveries were reduced in all years regardless of environmental flow strategy. The 40% FNF and functional flow strategies both increased water released to the river relative to baseline, but in different ways. The functional flow strategy allocated water in a holistic approach that enhanced ecological functions in all years, but particularly in moderate and wet years. In contrast, the 40% FNF strategy provided increased flows relative to baseline and some ecological benefit in dry years, but less ecological benefit in other years. This study shows that alternative environmental flow strategies will have different and important trade-offs for integrated water management, and may mutually benefit seemingly conflicting objectives.

Environmental flows are critical to the recovery and conservation of freshwater ecosystems worldwide. However, estimating the flows needed to sustain ecosystem health across large, diverse landscapes is challenging. To advance protections of environmental flows for streams in California, United States, we developed a statewide modeling approach focused on functional components of the natural flow regime. Functional flow components in California streams—fall pulse flows, wet season peak flows and base flows, spring recession flows, and dry season baseflows—support essential physical and ecological processes in riverine ecosystems. These functional flow components can be represented by functional flow metrics (FFMs) and quantified by their magnitude, timing, frequency, duration, and rate-of-change from daily streamflow records. After calculating FFMs at reference-quality streamflow gages in California, we used machine-learning methods to estimate their natural range of values for all stream reaches in the state based on physical watershed characteristics, and climatic factors. We found that the models performed well in predicting FFMs in streams across a diversity of landscape and climate contexts, according to a suite of model performance criteria. Using the predicted FFM values, we established initial estimates of ecological flows that are expected to support critical ecosystem functions and be broadly protective of ecosystem health. Modeling functional flows at large regional scales offers a pathway for increasing the pace and scale of environmental flow protections in California and beyond.

Conventional flood control has emphasized structural measures such as levees, reservoirs, and engineered channels—measures that typically simplify river channels and cut them off from their floodplain, both with adverse environmental consequences. Structural measures tend to be rigid and not easily adapted to increased flooding regimes resulting from environmental change. Such actions also limit the natural hydrologic benefits of floodplains such as storing floodwaters, improving water quality, providing habitat for invertebrates and fish during periods of inundation, and supporting a multitude of cultural services. As these benefits are more widely recognized, policies are being adopted to encourage projects that reduce flood risks and restore floodplain ecosystems, while acknowledging the social-ecological context. The number of such projects, however, remains small. We assessed four multi-benefit floodplain projects (two in California, United States, and two in Germany) and characterized their drivers, history, and measures implemented. In both United States cases, the dominant driver behind the project was flood risk reduction, and ecosystem restoration followed, in one case inadvertently, in the other as a requirement to receive a subsidy for a flood risk reduction project. One German case was motivated by ecosystem restoration, but it was more widely accepted because it also offered flood management benefits. The fourth case was conceived in terms of balanced goals of flood risk reduction, ecosystem restoration, and recreation. We conclude that projects that both reduce flood risk and restore ecosystems are clearly possible and often cost-effective, and that they could be more widely implemented. The principal barriers are often institutional and regulatory, rather than technical.

The article discusses the optimal scheduling of intensivists in critical care medicine and its impact on patient outcomes. It highlights previous studies that have examined the association between intensivist staffing and reduced hospital mortality. The article focuses on the number of consecutive days worked by intensivists and its effects on patient care and physician burnout. It presents a study that compares patient outcomes between 1-week and 2-week attending intensivist schedules and finds no significant differences in mortality, ICU length of stay, or duration of mechanical ventilation. The article acknowledges the limitations of the study and suggests future research to explore the impact of different schedules on patient experience and equity. Another article in the same journal discusses trends in ICU utilization and outcomes over a 12-year period using administrative databases. It reports a stable proportion of hospitalizations using ICU resources, a decline in hospital length of stay and mortality among ICU hospitalizations, and suggests a potential over-utilization of ICU care. The article acknowledges the complexity of the issue and the limitations of the data, but highlights the importance of addressing this issue in critical care medicine. [Extracted from the article]

Flow alteration is a pervasive issue across highly urbanized watersheds that can impact the physical and biological condition of streams. In highly altered systems, flows may support novel ecosystems that may not have been found under natural conditions and reference-based environmental flow targets may not be relevant. Moreover, stream impairments such as altered channel morphology may make reference-based environmental flow targets less effective in supporting ecosystem functions. Here, we develop an approach for determining ecological flow needs in highly modified systems to support existing ecological uses utilizing the California Environmental Flows Framework (CEFF). CEFF was established to provide guidance on developing environmental flow recommendations across California’s diverse physical landscape and broad array of management contexts. This paper illustrates the application of CEFF in informing ecologically-based flow restoration in a highly altered region of South Orange County, California. The steps of CEFF were implemented including a stakeholder process to establish goals and provide input throughout the project; identifying the natural ranges of functional flow metrics, or distinct components of the natural flow regime that support ecosystem functions; refining ecological flow needs to account for altered channel morphology and the life history needs of riparian and fish species; and assessing flow alteration to inform management strategies. Key considerations and lessons learned are discussed in the context of developing ecological flow needs in highly altered systems including when non-flow related management actions (i.e., channel rehabilitation) are necessary to achieve ecological goals.

Large state or regional environmental flow programs, such as the one based on the California Environmental Flows Framework, rely on broadly applicable relationships between flow and ecology to inform management decisions. California, despite having high flow and bioassessment data density, has not established relationships between specific elements of the annual hydrograph and biological stream condition. To address this, we spatially and temporally linked USGS gage stations and biological assessment sites in California to identify suitable paired sites for comparisons of streamflow alteration with biological condition at a statewide scale. Flows were assessed using a set of functional flow metrics that provide a comprehensive way to compare alteration and seasonal variation in streamflow across different locations. Biological response was evaluated using the California Stream Condition Index (CSCI) and Algal Stream Condition Index (ASCI), which quantify biological conditions by translating benthic invertebrate or algal resources and watershed-scale environmental data into an overall measure of stream health. These indices provide a consistent statewide standard for interpreting bioassessment data, and thus, a means of quantitatively comparing stream conditions throughout the state. The results indicate that indices of biological stream condition were most closely associated with flow alteration in seasonality and timing metrics, such as fall pulse timing, dry-season timing, and wet season timing. Magnitude metrics such as dry-season baseflow, wet season baseflow, and the fall pulse magnitude were also important in influencing biological stream conditions. Development of ecological flow needs in large-scale environmental programs should consider that alteration to any of the seasonal flow components (e.g., dry-season baseflow, fall pulse flow, wet-season baseflow, spring recession flow) may be important in restructuring biological communities.

Objectives We aimed to evaluate the personal, professional, and psychological impact of the COVID-19 pandemic on hospital workers and their perceptions about mitigating strategies. Design Cross-sectional web-based survey consisting of (1) a survey of the personal and professional impact of the COVID-19 pandemic and potential mitigation strategies, and (2) two validated psychological instruments (Kessler Psychological Distress Scale [K10] and Impact of Events Scale Revised [IES-R]). Regression analyses were conducted to identify the predictors of workplace stress, psychological distress, and post-traumatic stress. Setting and participants Hospital workers employed at 4 teaching and 8 non-teaching hospitals in Ontario, Canada during the COVID-19 pandemic. Results Among 1875 respondents (84% female, 49% frontline workers), 72% feared falling ill, 64% felt their job placed them at great risk of COVID-19 exposure, and 48% felt little control over the risk of infection. Respondents perceived that others avoided them (61%), reported increased workplace stress (80%), workload (66%) and responsibilities (59%), and 44% considered leaving their job. The psychological questionnaires revealed that 25% had at least some psychological distress on the K10, 50% had IES-R scores suggesting clinical concern for post-traumatic stress, and 38% fulfilled criteria for at least one psychological diagnosis. Female gender and feeling at increased risk due to PPE predicted all adverse psychological outcomes. Respondents favoured clear hospital communication (59%), knowing their voice is heard (55%), expressions of appreciation from leadership (55%), having COVID-19 protocols (52%), and food and beverages provided by the hospital (50%). Conclusions Hospital work during the COVID-19 pandemic has had important personal, professional, and psychological impacts. Respondents identified opportunities to better address information, training, and support needs.

Environmental flows, or the practice of allocating water in river systems for ecological purposes, is a leading strategy for conserving aquatic species and improving river health. However, consideration of surface-groundwater connectivity is seldom addressed in environmental flow development due to a lack of methodologies that account for groundwater contributions to instream flow. Groundwater-influenced streams have been identified as key refugia for native biota under a rapidly changing climate. These ecosystems are anticipated to be more resistant to climate change because groundwater input buffers the adverse effects of low flows and high temperatures, particularly in the dry season. Less understood, however, is the relative contribution of groundwater inputs to streamflow and how these surface-groundwater water interactions should be accounted for in environmental flow assessments and management actions. In order to assess ecological flow needs in groundwater-influenced streams, we applied the California Environmental Flows Framework (CEFF) in two river systems in California, United States. The Little Shasta River and the lower Cosumnes River are representative of many groundwater-influenced streams throughout the semi-arid western United States. Historically, perennial streamflow once sustained diverse native aquatic species in these ecosystems, but water withdrawals for irrigated agriculture has resulted in periodic stream dewatering. We found CEFF was useful in quantifying ecological flow needs for seasonal components of the flow regime that support ecosystem functionality. In particular, CEFF offered flexibility to incorporate information on the seasonal and spatial dimensions of groundwater influences in the development of ecological flow targets. The focus on ecosystem functions in CEFF, and ability to account for groundwater influences on those functions, creates opportunities for integrated surface-groundwater management strategies that support the recovery and protection of streamflows in groundwater-influenced streams.