Search

Scalloped hammerhead sharks Sphyrna lewini are a circumglobal species found in tropical and subtropical waters. Globally, populations of S. lewini have undergone dramatic declines in recent decades, and 4 of 6 distinct population segments are at risk of extinction and listed under the United States Endangered Species Act. Despite this, limited data exist on movement behavior or habitat use requirements of S. lewini, especially in the Central Pacific region. In this long-term (2009-2020) telemetry study, 27 S. lewini (24 males [22 adults, 2 juveniles], and 3 juvenile females) ranging in size from 106 to 310 cm (total length) were tagged with a combination of acoustic and/or satellite tags in a known nursery area, Kāne‘ohe Bay, Hawai‘i. Acoustic data revealed repeated movements of adult male S. lewini to Kāne‘ohe Bay between May and September across multiple years. Horizontal movements away from the Bay indicate these individuals are highly associated with the Hawaiian Archipelago (i.e. Northwestern and main Hawaiian Islands), while vertical movements were dynamic, with repeated, nocturnal deep dives to depths beyond 800 m and temperatures as low as 5.0°C. We conclude that adult male and juvenile S. lewini tagged in Kāne‘ohe Bay exhibit fairly restricted movements throughout the Hawaiian Archipelago, and mature males specifically exhibit strong seasonal site fidelity to Kāne‘ohe Bay. These data add crucial baseline information on habitat preferences of S. lewini around the Hawaiian Islands, and can be used to help structure conservation strategies for a portion of the Central Pacific population.

Some health concerns are often not identified until late into clinical development of drugs, which can place participants and patients at significant risk. For example, the United States Food and Drug Administration (FDA) labeled the xanthine oxidase inhibitor febuxostat with a"boxed" warning regarding an increased risk of cardiovascular death, and this safety risk was only identified during Phase 3b clinical trials after its approval. Thus, better preclinical assessment of drug efficacy and safety are needed to accurately evaluate candidate drug risk earlier in discovery and development. This study explored whether an in vitro vascular model incorporating human vascular cells and hemodynamics could be used to differentiate the potential cardiovascular risk associated with molecules that have similar on-target mechanisms of action. We compared the transcriptomic responses induced by febuxostat and other xanthine oxidase inhibitors to a database of 111 different compounds profiled in the human vascular model. Of the 111 compounds in the database, 107 are clinical-stage and 33 are FDA-labelled for increased cardiovascular risk. Febuxostat induces pathway-level regulation that has high similarity to the set of drugs FDA-labelled for increased cardiovascular risk. These results were replicated with a febuxostat analog, but not another structurally distinct xanthine oxidase inhibitor that does not confer cardiovascular risk. Together, these data suggest that the FDA warning for febuxostat stems from the chemical structure of the medication itself, rather than the target, xanthine oxidase. Importantly, these data indicate that cardiovascular risk can be evaluated in this in vitro human vascular model, which may facilitate understanding the drug candidate safety profile earlier in discovery and development.

Objectives Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.Design In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.Setting UK stroke services.Participants 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.Results Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.Conclusion It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration number ISRCTN83290762; Post-results.

Educational leadership, including special education leadership, could benefit from learning sciences and advanced technologies used in other fields (e.g., psychology, medicine). Despite over 30 years of research, leadership preparation is not yet incorporating critical knowledge from the learning sciences to understand the expert versus novice knowledge gap. This article embraces emotion as a cornerstone of leadership decision-making, which can be an impactful way to improve regulation and resilience in leadership preparation.

Objective: To identify the prevalence of anxiety, depression, and suicidal ideation that would place university students at risk for mental health disorders. To explore the source of stressors and possible interventions that may benefit student mental health in a university setting. Participants: University students (n = 483) who had been learning remotely due to the COVID-19 pandemic. Methods: A mixed-methods cross-sectional survey was administered in 2020. Results: Students were at an increased rate of depression, anxiety and suicidal ideation as compared to the general population. Female gender, lack of social support, living alone, being a first-generation college student and COVID-19 were significantly associated with mental health disorders. Stressors were identified and categorized into themes and interventions were recognized that may improve student well-being. Conclusion: Students enrolled in university programs appear to experience significant amounts of anxiety, depression, and suicidal ideation. Additional mental health education, resources, and support is needed.

Predatory journals are a blemish on scholarly publishing and academia and the studies published within them are more likely to contain data that is false. The inclusion of studies from predatory journals in evidence syntheses is potentially problematic due to this propensity for false data to be included. To date, there has been little exploration of the opinions and experiences of evidence synthesisers when dealing with predatory journals in the conduct of their evidence synthesis. In this paper, the thoughts, opinions, and attitudes of evidence synthesisers towards predatory journals and the inclusion of studies published within these journals in evidence syntheses were sought. Focus groups were held with participants who were experienced evidence synthesisers from JBI (previously the Joanna Briggs Institute) collaboration. Utilising qualitative content analysis, two generic categories were identified: predatory journals within evidence synthesis, and predatory journals within academia. Our findings suggest that evidence synthesisers believe predatory journals are hard to identify and that there is no current consensus on the management of these studies if they have been included in an evidence synthesis. There is a critical need for further research, education, guidance, and development of clear processes to assist evidence synthesisers in the management of studies from predatory journals.

The social movement toward cultural relativism has led to a growing distrust and even disbelief in the value of scientific inquiry regarding the effects of, or the need for, special education for students with disabilities. The authors examine the basic underpinnings of scientific methodology and its fundamental role in establishing best practice in the field. We also address contrary views and their risks and weaknesses. Scientific methodology is foundational to effective programs and services to marginalized students, including those with disabilities.

Abstract Background Cardiac fibromas are extremely rare in adults. The preferred treatment is surgical resection, but antiarrhythmic medications or heart transplantation have also been used previously. The cardiac imaging, particularly MRI, can be useful to help delineate between primary cardiac tumors, and surgical factors such as the extent/size of the fibroma, involvement of the coronary arteries or mitral apparatus and amount of residual myocardium influence whether surgical resection is feasible. Case presentation A 42-year-old male presented with a wide-complex tachycardia, unresponsive to amiodarone. An echocardiogram was performed which showed a possible posterior wall mass. A cardiac MRI showed a well circumscribed lateral wall intracardiac fibroma, measuring 5.2 × 5.1 × 3.8 cm with preserved function. Surgical resection was successful, and he was discharged without a defibrillator. Conclusions Cardiac fibromas are encapsulated tumors which do not infiltrate myocardium and should be surgically resected if possible.

Abstract Benign prostatic hyperplasia (BPH) may decrease patient quality of life and often leads to acute urinary retention and surgical intervention. While effective treatments are available, many BPH patients do not respond or develop resistance to treatment. To understand molecular determinants of clinical symptom persistence after initiating BPH treatment, we investigated gene expression profiles before and after treatments in the prostate transitional zone of 108 participants in the Medical Therapy of Prostatic Symptoms (MTOPS) Trial. Unsupervised clustering revealed molecular subgroups characterized by expression changes in a large set of genes associated with resistance to finasteride, a 5α-reductase inhibitor. Pathway analyses within this gene cluster found finasteride administration induced changes in fatty acid metabolism, amino acid metabolism, immune response, steroid hormone metabolism, and kinase activity within the transitional zone. We found that patients without this transcriptional response were highly likely to develop clinical progression, which is expected in 13.2% of finasteride-treated patients. Importantly, a patient’s transcriptional response to finasteride was associated with their pre-treatment kinase expression. Further, we identified novel expression signatures of finasteride resistance among the transcriptionally responded patients. These patients showed different gene expression profiles at baseline and increased prostate transitional zone volume compared to the patients who responded to the treatment. Our work suggests molecular mechanisms of clinical resistance to finasteride treatment that could be potentially helpful for personalized BPH treatment as well as new drug development to increase patient drug response.

Abstract Objectives The main goal of presurgical evaluation in drug‐resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource‐intensive tests available, ictal single‐photon emission computed tomography (SPECT) aids SOZ localization by measuring focal increases in blood flow within the SOZ via intravenous peri‐ictal radionuclide administration. Recent studies indicate that geographic and center‐specific factors impact utilization of these diagnostic procedures. Our study analyzed successful ictal SPECT acquisition (defined as peri‐ictal injection during inpatient admission) using surgery‐related data from the Pediatric Epilepsy Research Consortium (PERC) surgery database. We hypothesized that a high seizure burden, longer duration of video EEG monitoring (VEEG), and more center‐specific hours of SPECT availability would increase the likelihood of successful ictal SPECT. Methods We identified study participants (≤18 years of age) who underwent SPECT as part of their phase 1 VEEG from January 2018 to June 2022. We assessed association between ictal SPECT outcomes (success vs. failure) and variables including patient demographics, epilepsy history, and center‐specific SPECT practices. Results Phase 1 VEEG monitoring with ictal SPECT injection was planned in 297 participants and successful in 255 participants (85.86%). On multivariable analysis, the likelihood of a successful SPECT injection was higher in patients of non‐Hispanic ethnicity (p = 0.040), shorter duration VEEG (p = 0.004), and higher hours of available SPECT services (p

Abstract Despite advances in genomic sequencing and bioinformatics, conservation genomics is still often hindered by a reliance on non-invasive samples. The presence of exogenous DNA and the low quantity and poor quality of DNA in non-invasive samples have been a roadblock to sequencing, thereby limiting the potential for genomic monitoring of endangered species. Recent molecular advances, such as host DNA enrichment, hold promise for facilitating sequencing from non-invasive samples. We used the FecalSeq method to enrich DNA extracted from wild-collected fecal pellets of the imperiled New England cottontail and identified SNPs from 3RAD Sequencing. We obtained SNPs from rabbit pellets, including pellets that were collected in poor environmental conditions and samples that performed poorly with microsatellites. Measures of sequencing success improved with greater amounts of starting DNA and 32% of samples generated SNP genotypes that passed quality control filtering. Genotyping error rates were high, however, and the approach was unable to consistently distinguish unique individuals or matching genotypes, while it was suitable for recovering the expected population structure. Pairing FecalSeq enrichment with RADseq is a promising low-cost method for monitoring wild populations using non-invasive samples in an environmental context, but it may be better suited for informing conservation through population genomics.

Introduction: Esketamine has been approved in Australia and New Zealand as a third-line antidepressant treatment for treatment resistant depression. This study describes changes in quality of life, depressive symptoms and productivity in participants treated with esketamine in real-world settings. Methods: Participants were recruited from an esketamine early access program and had not responded to two or more different antidepressants and not received neurostimulation for their current depressive episode. Participants received esketamine for 16 weeks or longer. Data collected included Assessment of Quality-of-Life scale (AQoL-8D), Hamilton Depression Rating Scale (HAM-D) and Work Productivity Activity Index (WPAI). Results: Participants (n = 105) had a mean age of 38.7 years (standard deviation (SD) = 14.6) and were predominantly female (59.0%). The mean duration of major depressive disorder was 7.2 years (SD = 4.2) and almost half of participants had been treated with 3–5 prior therapies. After 16-weeks on esketamine, participants showed improvement of greater than 10% across all dimensions of AQoL-8D, HAM-D scores decreased 8.0 points, and activity impairment decreased 20.4% as measured by WPAI. Limitations: This was a non-randomized and unblinded study and may have selection and reporting bias. The population was not necessarily representative of the broader Australian and New Zealand population. It is not possible to determine if the results will be sustained or changed if participants received treatment for longer. Conclusions: Esketamine early access program participants, who were a real-world cohort with extensive prior treatment, showed clinically significant improvements in quality of life, depression severity and productivity after 16-weeks on treatment.

BackgroundAdolescence is a key developmental period that affects lifelong health and is impacted by adolescents regularly engaging with digital health information. Adolescents need digital health literacy (DHL) to effectively evaluate the quality and credibility of such information, and to navigate an increasingly complex digital health environment. Few educational resources exist to improve DHL, and few have involved adolescents during design. The co-design approach may hold utility through developing interventions with participants as design partners. ObjectiveThis project aimed to explore the co-design approach in developing an educational resource to improve adolescents’ DHL. MethodsAdolescents (12-17 years old) attended 4 interactive co-design workshops (June 2021-April 2022). Participant perspectives were gathered on DHL and the design of educational resources to improve it. Data generated were analyzed through content analysis to inform educational resource development. ResultsIn total, 27 participants from diverse backgrounds attended the workshops. Insight was gained into participants’ relationship with digital health information, including acceptance of its benefits and relevance, coupled with awareness of misinformation issues, revealing areas of DHL need. Participants provided suggestions for educational resource development that incorporated the most useful aspects of digital formats to develop skills across these domains. The following 4 themes were derived from participant perspectives: ease of access to digital health information, personal and social factors that impacted use, impacts of the plethora of digital information, and anonymity offered by digital sources. Initial participant evaluation of the developed educational resource was largely positive, including useful suggestions for improvement. ConclusionsCo-design elicited and translated authentic adolescent perspectives and design ideas into a functional educational resource. Insight into adolescents’ DHL needs generated targeted educational resource content, with engaging formats, designs, and storylines. Co-design holds promise as an important and empowering tool for developing interventions to improve adolescents’ DHL.

Social isolation causes profound changes in social behaviour in a variety of species. However, the genetic and molecular mechanisms modulating behavioural responses to social isolation and social recovery remain to be elucidated. Here, we quantified the behavioural response of vinegar flies to social isolation using two distinct protocols (social space preference and sociability, the spontaneous tendencies to form groups). We found that social isolation increased social space and reduced sociability. These effects of social isolation were reversible and could be reduced after 3 days of group housing. Flies with a loss of function of neuroligin3 (orthologue of autism-related neuroligin genes) with known increased social space in a socially enriched environment were still able to recover from social isolation. We also show that dopamine (DA) is needed for a response to social isolation and recovery in males but not in females. Furthermore, only in males, DA levels are reduced after isolation and are not recovered after group housing. Finally, in socially enriched flies mutant for neuroligin3, DA levels are reduced in males, but not in females. We propose a model to explain how DA and neuroligin3 are involved in the behavioural response to social isolation and its recovery in a dynamic and sex-specific manner.

A systematic review was conducted to examine the association between fish oil supplementation and the development of asthma exacerbations. Comprehensive literature reviews of recent fish oil studies were performed to evaluate alterations in asthma surrogate markers. Additionally, the relative compositions of the fish oils used in each study were analyzed. The results of the review were inconclusive, but provide a basis for future research methods.

The Eukaryotic RecA-like proteins Rad51 and Dmc1 cooperate during meiosis to promote recombination between homologous chromosomes by repairing programmed DNA double strand breaks (DSBs). Previous studies showed that Rad51 and Dmc1 form partially overlapping co-foci. Here we show these Rad51-Dmc1 co-foci are often arranged in pairs separated by distances of up to 400 nm. Paired co-foci remain prevalent when DSBs are dramatically reduced or when strand exchange or synapsis is blocked. Super-resolution dSTORM microscopy reveals that individual foci observed by conventional light microscopy are often composed of two or more substructures. The data support a model in which the two tracts of ssDNA formed by a single DSB separate from one another by distances of up to 400 nm, with both tracts often bound by one or more short (about 100 nt) Rad51 filaments and also by one or more short Dmc1 filaments.

ObjectiveThe authors of this study evaluated the safety and efficacy of stereotactic laser ablation (SLA) for the treatment of drug-resistant epilepsy (DRE) in children.MethodsSeventeen North American centers were enrolled in the study. Data for pediatric patients with DRE who had been treated with SLA between 2008 and 2018 were retrospectively reviewed.ResultsA total of 225 patients, mean age 12.8 ± 5.8 years, were identified. Target-of-interest (TOI) locations included extratemporal (44.4%), temporal neocortical (8.4%), mesiotemporal (23.1%), hypothalamic (14.2%), and callosal (9.8%). Visualase and NeuroBlate SLA systems were used in 199 and 26 cases, respectively. Procedure goals included ablation (149 cases), disconnection (63), or both (13). The mean follow-up was 27 ± 20.4 months. Improvement in targeted seizure type (TST) was seen in 179 (84.0%) patients. Engel classification was reported for 167 (74.2%) patients; excluding the palliative cases, 74 (49.7%), 35 (23.5%), 10 (6.7%), and 30 (20.1%) patients had Engel class I, II, III, and IV outcomes, respectively. For patients with a follow-up ≥ 12 months, 25 (51.0%), 18 (36.7%), 3 (6.1%), and 3 (6.1%) had Engel class I, II, III, and IV outcomes, respectively. Patients with a history of pre-SLA surgery related to the TOI, a pathology of malformation of cortical development, and 2+ trajectories per TOI were more likely to experience no improvement in seizure frequency and/or to have an unfavorable outcome. A greater number of smaller thermal lesions was associated with greater improvement in TST. Thirty (13.3%) patients experienced 51 short-term complications including malpositioned catheter (3 cases), intracranial hemorrhage (2), transient neurological deficit (19), permanent neurological deficit (3), symptomatic perilesional edema (6), hydrocephalus (1), CSF leakage (1), wound infection (2), unplanned ICU stay (5), and unplanned 30-day readmission (9). The relative incidence of complications was higher in the hypothalamic target location. Target volume, number of laser trajectories, number or size of thermal lesions, or use of perioperative steroids did not have a significant effect on short-term complications.ConclusionsSLA appears to be an effective and well-tolerated treatment option for children with DRE. Large-volume prospective studies are needed to better understand the indications for treatment and demonstrate the long-term efficacy of SLA in this population.

Phosphates and polyphosphates play ubiquitous roles in biology as integral structural components of cell membranes and bone, or as vehicles of energy storage via adenosine triphosphate and phosphocreatine. The solution phase space of phosphate species appears more complex than previously known. We present nuclear magnetic resonance (NMR) and cryogenic transmission electron microscopy (cryo-TEM) experiments that suggest phosphate species including orthophosphates, pyrophosphates, and adenosine phosphates associate into dynamic assemblies in dilute solutions that are spectroscopically "dark." Cryo-TEM provides visual evidence of the formation of spherical assemblies tens of nanometers in size, while NMR indicates that a majority population of phosphates remain as unassociated ions in exchange with spectroscopically invisible assemblies. The formation of these assemblies is reversibly and entropically driven by the partial dehydration of phosphate groups, as verified by diffusion-ordered spectroscopy (DOSY), indicating a thermodynamic state of assembly held together by multivalent interactions between the phosphates. Molecular dynamics simulations further corroborate that orthophosphates readily cluster in aqueous solutions. This study presents the surprising discovery that phosphate-containing molecules, ubiquitously present in the biological milieu, can readily form dynamic assemblies under a wide range of commonly used solution conditions, highlighting a hitherto unreported property of phosphate's native state in biological solutions.

Years ago, it became established that the severity and length of the Great Depression were due largely to misguided Federal Reserve monetary policy and the resulting catastrophic bank failures. This result is confirmed by surveys of scholars in the area and books specifically written on economic history. Yet the leading textbooks used in high school US history fail to reflect these findings. The texts (1) tend to ignore the recognized causes of the Great Depression's severity and (2) overstate the role of other causes rejected by the majority of economic historians. After laying out this curious disjuncture, this article presents curricular resources to help high school teachers more accurately present the Great Depression's causes.