This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death ...determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists’ Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society.
Coral reefs are among the most diverse and iconic ecosystems on Earth, but a range of anthropogenic pressures are threatening their persistence. Owing to their remoteness, broad spatial coverage and ...cross‐jurisdictional locations, there are no high‐resolution remotely sensed maps available at the global scale. Here we present a framework that is capable of mapping coral reef habitats from individual reefs (~200 km2) to entire barrier reef systems (200 000 km2) and across vast ocean extents (>6 000 000 km2). This is the first time this has been demonstrated using a consistent and transparent remote sensing mapping framework. The ten maps that we present achieved good accuracy (78% mean overall accuracy) from multiple input image datasets and training data sources, and our framework was shown to be adaptable to either benthic or geomorphic reef features and across diverse coral reef environments. These new generation high‐resolution map data will be useful for supporting ecosystem risk assessments, detecting change in ecosystem dynamics and targeting efforts to monitor local‐scale changes in coral cover and reef health.
Here we present a mapping framework for coral reefs from the scale of individual reefs to the entire reef systems across millions of square kilometers of ocean. The framework can utilize a wide range of input covariate and training data sources, and outputs both geomorphic and benthic map types. The maps presented are the largest ever coral reefs maps produced from a consistent and transparent remote sensing approach.
•Sorafenib did not significantly improve the EFS when added to intensive chemotherapy for newly diagnosed FLT3-ITD AML.•FLT3-ITD MRD clearance as assessed by polymerase chain reaction–next-generation ...sequencing has powerful prognostic utility in determining survival outcome.
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Sorafenib maintenance improves outcomes after hematopoietic cell transplant (HCT) for patients with FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML). Although promising outcomes have been reported for sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) randomized 102 patients (aged 18-65 years) 2:1 to sorafenib vs placebo (days 4-10) combined with intensive induction: idarubicin 12 mg/m2 on days 1 to 3 plus cytarabine 1.5 g/m2 twice daily on days 1, 3, 5, and 7 (18-55 years) or 100 mg/m2 on days 1 to 7 (56-65 years) as consolidation therapy, followed by maintenance treatment for 12 months (post-HCT excluded) in newly diagnosed FLT3-ITD AML. Four patients were excluded from the modified intention-to-treat final analysis (3 not dosed and 1 later tested negative for FLT3-ITD). Rates of complete remission (CR)/CR with incomplete hematologic recovery were high in both arms (sorafenib, 78%/9%; placebo, 70%/24%, respectively). With a 49.1-month median follow-up, the primary end point of event-free survival (EFS) was not improved by sorafenib (2-year EFS, 47.9% vs 45.4%; hazard ratio HR, 0.87; 95% confidence interval CI, 0.51-1.51; P = .61). Two-year overall survival (OS) was 67% in the sorafenib arm and 58% in the placebo arm (HR, 0.76; 95% CI, 0.42-1.39). For patients who received transplantation in the first remission, the 2-year OS rates were 84% and 67% in the sorafenib and placebo arms, respectively (HR, 0.45; 95% CI, 0.18-1.12; P = .08). In exploratory analyses, FLT3-ITD measurable residual disease (MRD) negative status (<0.001%) after induction was associated with an improved 2-year OS (83% vs 60%; HR, 0.4; 95% CI, 0.17-0.93; P = .028). In conclusion, routine use of pretransplant sorafenib plus chemotherapy in unselected patients with FLT3-ITD AML is not supported by this study.
Phenotyping technologies featured in the diagnosis of inborn errors of metabolism, such as organic acid, amino acid, and acylcarnitine analyses, recently have been supplemented by broad-scale ...untargeted metabolomic phenotyping. We investigated the analyte changes associated with aromatic amino acid decarboxylase (AADC) deficiency and dopamine medication treatment.
Using an untargeted metabolomics platform, we analyzed ethylenediaminetetraacetic acid plasma specimens, and biomarkers were identified by comparing the biochemical profile of individual patient samples to a pediatric-centric population cohort.
Elevated 3-methoxytyrosine (average z score 5.88) accompanied by significant decreases of dopamine 3-O-sulfate (−2.77), vanillylmandelate (−2.87), and 3-methoxytyramine sulfate (−1.44) were associated with AADC deficiency in three samples from two patients. In five non-AADC patients treated with carbidopa-levodopa, levels of 3-methoxytyrosine were elevated (7.65); however, the samples from non-AADC patients treated with DOPA-elevating drugs had normal or elevated levels of metabolites downstream of aromatic l-amino acid decarboxylase, including dopamine 3-O-sulfate (2.92), vanillylmandelate (0.33), and 3-methoxytyramine sulfate (5.07). In one example, a plasma metabolomic phenotype pointed to a probable AADC deficiency and prompted the evaluation of whole exome sequencing data, identifying homozygosity for a known pathogenic variant, whereas whole exome analysis in a second patient revealed compound heterozygosity for two variants of unknown significance.
These data demonstrate the power of combining broad-scale genotyping and phenotyping technologies to diagnose inherited neurometabolic disorders and suggest that metabolic phenotyping of plasma can be used to identify AADC deficiency and to distinguish it from non-AADC patients with elevated 3-methoxytyrosine caused by DOPA-raising medications.
Urocanic aciduria is caused by a deficiency in the enzyme urocanase (E.C. 4.2.1.49) encoded by the gene UROC1. In the past, deficiency of urocanase has been associated with intellectual disability in ...a few case studies with some suggestion that the enzyme deficiency was the causative etiology. Here, we describe two phenotypically normal siblings with compound heterozygous pathogenic variants in UROC1 and characteristic biochemical evidence of urocanase deficiency collected utilizing untargeted metabolomic analysis. These findings suggest that urocanic aciduria may represent an otherwise benign biochemical phenotype and that those individuals with concurrent developmental delay should continue to be evaluated for other underlying causes for their symptoms.
Previous research has demonstrated restorative effects of music, showing that exposure to music yields mental health benefits that include improvement in stress management. However, it remains ...unclear whether the benefits of “on the spot” music interventions extend to cognitive performance. The present study explored whether music can be applied as a low-cost, non-invasive “on the spot” intervention to improve cognitive performance and physiological effects. Specifically, studies has yet to examine whether the effects of different genres of focus music extend beyond stress management to include cognitive performance and physiological effects. To address this gap in the literature, the current study recruited 120 healthy adults in a fully randomized procedure involving three experimental groups of participants and a control group. Each experimental group was exposed to one specific genre of focus music compared to a no-music control group. In a between-group design, the study exposed three separate groups to
jazz music
,
piano music
, and
lo-fi music
respectively. The fourth group was a no-music control group. The study employed a 3-day experimental procedure and a follow-up procedure in which participants completed two attention monitoring tasks. Participants completed focus music interventions with a duration of 15 and 45 min. The follow-up procedure aimed to experimentally induce music familiarity and probe its effect on cognitive performance. To assess cardiovascular effects, heart rate variability (HRV) data was collected during the music intervention period and during a baseline period. Results showed performance differences across the three active music groups on the sustained attention to response task (SART) compared to the no-music control group. Furthermore, the study showed a physiological effect in the direction of increased parasympathetic activity indexed as an increased HRV response in the three active music groups compared to the no-music control group, adding to convergent lines of evidence suggesting that music can enhance parasympathetic activity and cognitive performance. In addition, the study found that music familiarity (relative to music unfamiliarity) influenced cognitive performance in the direction of faster reaction times (RTs)
during
the music intervention period in which participants were exposed to the attentional network task (ANT) and an increase in the physiological response in the familiar relative to the unfamiliar music condition. In summary, the study found evidence of a pronounced effect of three types of focus music on both cognitive performance and the underlying physiological response. Thus, focus music holds promise as an evidence-based intervention offering mental health benefits through physiological improvements and enhancement of cognitive processing.
Objectives:
Anorexia nervosa is a severe psychiatric disorder with high mortality rates. While its aetiology is poorly understood, there is evidence of a significant genetic component. The Anorexia ...Nervosa Genetics Initiative is an international collaboration which aims to understand the genetic basis of the disorder. This paper describes the recruitment and characteristics of the Australasian Anorexia Nervosa Genetics Initiative sample, the largest sample of individuals with anorexia nervosa ever assembled across Australia and New Zealand.
Methods:
Participants completed an online questionnaire based on the Structured Clinical Interview Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) eating disorders section. Participants who met specified case criteria for lifetime anorexia nervosa were requested to provide a DNA sample for genetic analysis.
Results:
Overall, the study recruited 3414 Australians and 543 New Zealanders meeting the lifetime anorexia nervosa case criteria by using a variety of conventional and social media recruitment methods. At the time of questionnaire completion, 28% had a body mass index ⩽ 18.5 kg/m2. Fasting and exercise were the most commonly employed methods of weight control, and were associated with the youngest reported ages of onset. At the time of the study, 32% of participants meeting lifetime anorexia nervosa case criteria were under the care of a medical practitioner; those with current body mass index < 18.5 kg/m2 were more likely to be currently receiving medical care (56%) than those with current body mass index ⩾ 18.5 kg/m2 (23%). Professional treatment for eating disorders was most likely to have been received from general practitioners (45% of study participants), dietitians (42%) and outpatient programmes (42%).
Conclusions:
This study was effective in assembling the largest community sample of people with lifetime anorexia nervosa in Australia and New Zealand to date. The proportion of people with anorexia nervosa currently receiving medical care, and the most common sources of treatment accessed, indicates the importance of training for general practitioners and dietitians in treating anorexia nervosa.
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