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Background and objective Although mental health is always a major concern, particularly for airline pilots, knowledge of and attitudes toward mental health have not always been emphasized for safe operations in the aviation industry. Fear of self-reporting, stigmas, and lack of knowledge about mental health conditions are prevalent in this industry. The purpose of our research was to examine pilots' perceptions of mental health issues, the resources available to them, and the reasons they may or may not report these issues. Methods We conducted a qualitative, phenomenological study in which 21 commercial pilots were interviewed to better understand their perceptions of mental health issues, available self-help resources, and rationale for failing to report mental health issues. Results The results of our analysis using NVivo software showed that pilots neither reported the issues nor trusted the processes meant to address mental health issues. Three themes emerged from the research: (1) pilots avoid discussing mental health issues for fear of repercussions, (2) although resources exist, pilots generally distrust the confidentiality of reporting systems, and (3) pilots honestly believe that reporting any mental health issue will be devastating to their careers. Conclusions Airline companies and the Federal Aviation Administration (FAA) need to change processes and instill a sense of trust in reporting systems among pilots so that they feel safe reporting mental health concerns and receive improved treatment. This can lead to more accurate reporting of conditions and ensure safe flight operations.
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Species distribution models are vital to management decisions that require understanding habitat use patterns, particularly for species of conservation concern. However, the production of distribution maps for individual species is often hampered by data scarcity, and existing species maps are rarely spatially validated due to limited occurrence data. Furthermore, community-level maps based on stacked species distribution models lack important community assemblage information (e.g., competitive exclusion) relevant to conservation. Thus, multispecies, guild, or community models are often used in conservation practice instead. To address these limitations, we aimed to generate fine-scale, spatially continuous, nationwide maps for species represented in the North American Breeding Bird Survey (BBS) between 1992 and 2019. We developed ensemble models for each species at three spatial resolutions-0.5, 2.5, and 5 km-across the conterminous United States. We also compared species richness patterns from stacked single-species models with those of 19 functional guilds developed using the same data to assess the similarity between predictions. We successfully modeled 192 bird species at 5-km resolution, 160 species at 2.5-km resolution, and 80 species at 0.5-km resolution. However, the species we could model represent only 28%-56% of species found in the conterminous US BBSs across resolutions owing to data limitations. We found that stacked maps and guild maps generally had high correlations across resolutions (median = 84%), but spatial agreement varied regionally by resolution and was most pronounced between the East and West at the 5-km resolution. The spatial differences between our stacked maps and guild maps illustrate the importance of spatial validation in conservation planning. Overall, our species maps are useful for single-species conservation and can support fine-scale decision-making across the United States and support community-level conservation when used in tandem with guild maps. However, there remain data scarcity issues for many species of conservation concern when using the BBS for single-species models.
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Aves , Ecossistema , Animais , Estados UnidosRESUMO
To fabricate optical components with surface layers compatible with high-power laser applications that may operate as antireflective coatings, polarization rotators, or harness physical anisotropy for other uses, metasurfaces are becoming an appealing candidate. In this study, large-beam (1.05 cm diameter) 351-nm laser-induced damage testing was performed on an all-glass metasurface structure composed of cone-like features with a subwavelength spacing of adjacent features. These structures were fabricated on untreated fused silica glass and damage tested, as were structures that were fabricated on fused silica glass that experienced a preliminary etching process to remove the surface Beilby layer that is characteristic of polished fused silica. The laser-induced damage onset for structures on untreated fused silica glass was 19.3Jâ c m -2, while the sample that saw an initial pretreatment etch exhibited an improved damage onset of 20.4Jâ c m -2, only 6% short of the reference pretreated glass damage onset of 21.7Jâ c m -2. For perspective, the National Ignition Facility operational average fluence at this wavelength and pulse length is about 10J/c m 2. At a fluence of 25.5Jâ c m -2, the reference (pretreated) fused silica initiated 5.2 damage sites per m m 2, while the antireflective metasurface sample with a preliminary etching process treatment initiated 9.8 damage sites per m m 2. These findings demonstrate that substrate-engraved metasurfaces are compatible with high energy and power laser applications, further broadening their application space.
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Since their introduction into the United States in the early 1900's, imported fire ants, namely Solenopsis invicta Buren (Red Imported Fire Ant), S. richteri Forel (Black Imported Fire Ant), and their hybrid form Solenopsis invicta X richteri have spread throughout portions of the USA, especially in the southeastern region. Imported fire ants are a serious invasive and economically significant species in the USA and elsewhere, and their spread into new parts of the country is of great concern. Although early models predicted that the fire ants would not be able to survive very far north into the USA, these ants have nonetheless successfully continued their spread into higher latitudes. Based on Cooperative Agricultural Pest Survey (CAPS) samples, the Mississippi Entomological Museum Invasive Insect Screening Center, at Mississippi State University, has verified the presence of imported fire ants collected in Kentucky at multiple locations from 2014 to 2022.
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The tawny crazy ant, Nylanderia fulva (Mayr) (Hymenoptera: Formicidae) has a native range that extends from northern Argentina to southern Brazil. In the U.S.A. this species has often been misidentified as Nylanderia (Paratrechina) pubens or N. cf. pubens and has likely been present in Florida and Texas for several decades [1]. In the early 2000's explosive population growth in Texas and neighboring states drew renewed taxonomic focus. Genetic analyses [2,3] aided in identifying the pest species as N. fulva. This species poses an invasive threat to native flora and fauna and human structures. In its invasive range it has been reported to displace another invasive species, the red imported fire ant. The specimens used for genome sequencing were obtained from the coastal region of Mississippi. DNA was extracted from pupae. The genome data set was deposited to the National Center for Biotechnology Information as submission ID: SUB10775679, Project ID: PRJNA796544, Accession IDs: SAMN24895442 and JAKFQQ000000000. The organism taxid is 613905, locus tag prefixes are L1K79. The assembly, USDA_Nfulva_1.0, was generated in collaboration with Dovetail Genomics (now Cantata Bio) to yield a chromosome-level assembly of 375 Mb with a 15.67 Mb N50 and 78X coverage and revealing 16 putative chromosomes. This high-quality chromosome-level genome assembly was released prior to publication as a public service to the research community.
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BACKGROUND: Despite rapid technological advances and growth, quality in imaging has not received the focus seen elsewhere in cardiovascular medicine, resulting in significant gaps between guidelines and practice. Contemporary echocardiography practice requires comprehensive real-time data collection to allow dynamic auditing and benchmarking of key performance indices. The American College of Cardiology (ACC) proposed additional data standardisation, structured reporting identifying key data elements and imaging registries. In the absence of an Australian echocardiography registry, we developed a national clinical quality registry (GenesisCare Cardiovascular Outcomes Echo Registry). We hypothesised that measurement and local reporting of data would improve compliance of echo studies with quality guidelines and hence their clinical value. METHODS AND RESULTS: We prospectively collected data on 4 099 281 echocardiographic studies entered directly into a central electronic database from 63 laboratories across four Australian states between 2010 and 2021. Real-time auditing of key data elements and introduction of quality improvement pathways were performed to maximise completeness and uniformity of data acquisition and reporting. We compared completeness of key data element acquisition (AV peak velocity, left ventricular ejection fraction, E/e', LA area, rhythm, RVSP) by time and state using de-identified data. Key performance outcomes benchmarked against the aggregated study cohort and international standards were reported to individual sites to drive quality improvement. Between 2010 and 2014 there were significant improvements in data completeness (72.0%+/-26.8% vs 86.8%+/-13.5%, p=0.02), which were maintained to 2020. In addition, interstate variability fell for both EF and E/e' (p<0.002). CONCLUSIONS: This large-scale collaboration provides a platform for the development of major quality improvement initiatives in echocardiography. Introduction of local quality assurance programmes via a unified national data set significantly improved the completeness of reporting of key echo quality measures. This in turn significantly improved the quality of, and reduced the interstate variability of, echo data. Developing a centralised database allowed rapid adoption nationally of local quality improvements.
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Ecocardiografia , Função Ventricular Esquerda , Austrália , Humanos , Sistema de Registros , Volume Sistólico , Estados UnidosRESUMO
Human activities alter ecosystems everywhere, causing rapid biodiversity loss and biotic homogenization. These losses necessitate coordinated conservation actions guided by biodiversity and species distribution spatial data that cover large areas yet have fine-enough resolution to be management-relevant (i.e., ≤5 km). However, most biodiversity products are too coarse for management or are only available for small areas. Furthermore, many maps generated for biodiversity assessment and conservation do not explicitly quantify the inherent tradeoff between resolution and accuracy when predicting biodiversity patterns. Our goals were to generate predictive models of overall breeding bird species richness and species richness of different guilds based on nine functional or life-history-based traits across the conterminous United States at three resolutions (0.5, 2.5, and 5 km) and quantify the tradeoff between resolution and accuracy and, hence, relevance for management of the resulting biodiversity maps. We summarized 18 years of North American Breeding Bird Survey data (1992-2019) and modeled species richness using random forests, including 66 predictor variables (describing climate, vegetation, geomorphology, and anthropogenic conditions), 20 of which we newly derived. Among the three spatial resolutions, the percentage variance explained ranged from 27% to 60% (median = 54%; mean = 57%) for overall species richness and 12% to 87% (median = 61%; mean = 58%) for our different guilds. Overall species richness and guild-specific species richness were best explained at 5-km resolution using ~24 predictor variables based on percentage variance explained, symmetric mean absolute percentage error, and root mean square error values. However, our 2.5-km-resolution maps were almost as accurate and provided more spatially detailed information, which is why we recommend them for most management applications. Our results represent the first consistent, occurrence-based, and nationwide maps of breeding bird richness with a thorough accuracy assessment that are also spatially detailed enough to inform local management decisions. More broadly, our findings highlight the importance of explicitly considering tradeoffs between resolution and accuracy to create management-relevant biodiversity products for large areas.
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Aves , Ecossistema , Animais , Biodiversidade , Atividades Humanas , Humanos , Estados UnidosRESUMO
INTRODUCTION: This study examined the safety and pharmacodynamic effects of selective muscarinic M1 receptor orthosteric agonist HTL0018318 in 60 patients with mild-to-moderate Alzheimer's disease (AD) on background donepezil 10 mg/day. METHODS: A randomized, double-blind, placebo-controlled 4-week safety study of HTL0018318 with up-titration and maintenance phases, observing exploratory effects on electrophysiological biomarkers and cognition. RESULTS: Treatment-emergent adverse events (TEAEs) were mild and less frequently reported during maintenance versus titration. Headache was most commonly reported (7-21%); 0 to 13% reported cholinergic TEAEs (abdominal pain, diarrhea, fatigue, nausea) and two patients discontinued due to TEAEs. At 1 to 2 hours post-dose, HTL0018318-related mean maximum elevations in systolic and diastolic blood pressure of 5 to 10 mmHg above placebo were observed during up-titration but not maintenance. Postive effects of HTL0018318 were found on specific attention and memory endpoints. DISCUSSION: HTL0018318 was well tolerated in mild-to-moderate AD patients and showed positive effects on attention and episodic memory on top of therapeutic doses of donepezil.
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Previous studies have described reverse-transcription loop-mediated isothermal amplification (RT-LAMP) for the rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal/oropharyngeal swab and saliva samples. This multisite clinical evaluation describes the validation of an improved sample preparation method for extraction-free RT-LAMP and reports clinical performance of four RT-LAMP assay formats for SARS-CoV-2 detection. Direct RT-LAMP was performed on 559 swabs and 86,760 saliva samples and RNA RT-LAMP on extracted RNA from 12,619 swabs and 12,521 saliva samples from asymptomatic and symptomatic individuals across health care and community settings. For direct RT-LAMP, overall diagnostic sensitivity (DSe) was 70.35% (95% CI, 63.48%-76.60%) on swabs and 84.62% (95% CI, 79.50%-88.88%) on saliva, with diagnostic specificity of 100% (95% CI, 98.98%-100.00%) on swabs and 100% (95% CI, 99.72%-100.00%) on saliva, compared with quantitative RT-PCR (RT-qPCR); analyzing samples with RT-qPCR ORF1ab CT values of ≤25 and ≤33, DSe values were 100% (95% CI, 96.34%-100%) and 77.78% (95% CI, 70.99%-83.62%) for swabs, and 99.01% (95% CI, 94.61%-99.97%) and 87.61% (95% CI, 82.69%-91.54%) for saliva, respectively. For RNA RT-LAMP, overall DSe and diagnostic specificity were 96.06% (95% CI, 92.88%-98.12%) and 99.99% (95% CI, 99.95%-100%) for swabs, and 80.65% (95% CI, 73.54%-86.54%) and 99.99% (95% CI, 99.95%-100%) for saliva, respectively. These findings demonstrate that RT-LAMP is applicable to a variety of use cases, including frequent, interval-based direct RT-LAMP of saliva from asymptomatic individuals who may otherwise be missed using symptomatic testing alone.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Teste para COVID-19 , Humanos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , RNA Viral/análise , RNA Viral/genética , SARS-CoV-2/genética , Saliva , Sensibilidade e EspecificidadeRESUMO
Current therapies for Alzheimer's disease seek to correct for defective cholinergic transmission by preventing the breakdown of acetylcholine through inhibition of acetylcholinesterase, these however have limited clinical efficacy. An alternative approach is to directly activate cholinergic receptors responsible for learning and memory. The M1-muscarinic acetylcholine (M1) receptor is the target of choice but has been hampered by adverse effects. Here we aimed to design the drug properties needed for a well-tolerated M1-agonist with the potential to alleviate cognitive loss by taking a stepwise translational approach from atomic structure, cell/tissue-based assays, evaluation in preclinical species, clinical safety testing, and finally establishing activity in memory centers in humans. Through this approach, we rationally designed the optimal properties, including selectivity and partial agonism, into HTL9936-a potential candidate for the treatment of memory loss in Alzheimer's disease. More broadly, this demonstrates a strategy for targeting difficult GPCR targets from structure to clinic.
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Doença de Alzheimer/tratamento farmacológico , Desenho de Fármacos , Receptor Muscarínico M1/agonistas , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Sequência de Aminoácidos , Animais , Pressão Sanguínea/efeitos dos fármacos , Células CHO , Inibidores da Colinesterase/farmacologia , Cricetulus , Cristalização , Modelos Animais de Doenças , Cães , Donepezila/farmacologia , Eletroencefalografia , Feminino , Células HEK293 , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Modelos Moleculares , Simulação de Dinâmica Molecular , Degeneração Neural/complicações , Degeneração Neural/patologia , Primatas , Ratos , Receptor Muscarínico M1/química , Transdução de Sinais , Homologia Estrutural de ProteínaRESUMO
BACKGROUND: Juvenile justice (JJ) youth are at high risk of opioid and other substance use (SU), dysfunctional family/social relationships, and complex trauma. The purpose of the Leveraging Safe Adults (LeSA) Project is to examine the effectiveness of Trust-Based Relational Intervention® (TBRI®; leveraging family systems by providing emotional and instrumental guidance, support, and role modeling) in preventing opioid and other SU among youth after release from secure residential facilities. METHODS: An effectiveness-implementation Hybrid Type 1 design is used to test the effectiveness of TBRI for preventing non-medical use of opioids among JJ-youth (delayed-start at the site level; a randomized controlled trial at participant level) and to gain insight into facility-level barriers to TBRI implementation as part of JJ re-entry protocols. Recruitment includes two samples (effectiveness: 360 youth/caregiver dyads; implementation: 203 JJ staff) from nine sites in two states over 3 years. Participant eligibility includes 15 to 18-year-olds disposed to community supervision and receiving care in a secure JJ facility, without active suicide risk, and with one caregiver willing to participate. Effectiveness data come from (1) youth and caregiver self-report on background, SU, psychosocial functioning, and youth-caregiver relationships (Months 0, 3, 6, 12, and 18), youth monthly post-release check-ins, and caregiver report on youth psychological/behavioral symptoms, and (2) JJ facility records (e.g., recidivism, treatment utilization). Fidelity assessment includes post-session checklists and measures of TBRI strategy use. Collected four times over four years, implementation data include (1) JJ staff self-report on facility and staff characteristics, use of trauma-informed care and TBRI strategies, and (2) focus groups (line staff, leadership separately) on use of trauma-informed strategies, uptake of new interventions, and penetration, sustainment, and expansion of TBRI practices. DISCUSSION: The LeSA study is testing TBRI as a means to empower caregivers to help prevent opioid use and other SU among JJ-youth. TBRI's multiple components offer an opportunity for caregivers to supplement and extend gains during residential care. If effective and implemented successfully, the LeSA protocol will help expand the application of TBRI with a wider audience and provide guidance for implementing multi-component interventions in complex systems spanning multiple contexts. TRIAL REGISTRATION: ClinicalTrials.gov NCT04678960 ; registered November 11, 2020; https://clinicaltrials.gov/ct2/show/NCT04678960 .
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Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Adolescente , Adulto , Cuidadores , Grupos Focais , Humanos , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , ViolênciaRESUMO
INTRODUCTION: HTL0018318 is a selective muscarinic M1 receptor partial agonist under development for the symptomatic treatment of dementias, including Alzheimer's disease. Clinically, HTL0018318 would likely be used alone or in conjunction with cholinesterase inhibitors (e.g. donepezil). OBJECTIVE: We investigated the safety, tolerability, and pharmacokinetics of HTL0018318 given alone and in combination with donepezil. METHODS: This was a randomized, double-blind, placebo-controlled trial in 42 (to deliver 36 with combination treatment) healthy elderly subjects investigating the effects of oral HTL0018318 15 and 25 mg given alone and combined with donepezil 10 mg at steady state on adverse events (AEs), vital signs, saliva production, sleep quality, pulmonary function, subjective feelings, and pharmacokinetics. RESULTS: AEs were reported by lower percentages of subjects after HTL0018318 alone than after donepezil alone. There was no increase in the percentage of subjects reporting AEs after co-administration than after donepezil alone. Supine systolic blood pressure was 1.6 mmHg (95% confidence interval [CI] -3.1 to -0.1) lower after HTL0018318 alone than after combination treatment. This was comparable with results from placebo alone: 1.7 mmHg (95% CI -3.2 to 0.2) lower than with combination treatment. Supine pulse rate was 3.3 bpm (95% CI 1.5-5.1) higher after HTL0018318 alone than with co-administration. HTL0018318 and donepezil did not meaningfully affect each other's pharmacokinetics. CONCLUSION: HTL0018318 was well tolerated when given alone and in combination with donepezil. HTL0018318 and donepezil do not demonstrate pharmacokinetic or pharmacodynamic interactions, indicating that HTL0018318 can be safely administered in combination with donepezil. CLINICAL TRIAL REGISTRATION: Netherlands Trial register identifier NL5915, registered on 28 October 2016.
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Doença de Alzheimer , Indanos , Idoso , Inibidores da Colinesterase/efeitos adversos , Donepezila/efeitos adversos , Método Duplo-Cego , Humanos , Indanos/efeitos adversos , Piperidinas/efeitos adversosRESUMO
BACKGROUND: The cholinergic system and M1 receptor remain an important target for symptomatic treatment of cognitive dysfunction. The selective M1 receptor partial agonist HTL0018318 is under development for the symptomatic treatment of Dementia's including Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). We investigated the safety, tolerability, pharmacokinetics and exploratory pharmacodynamics of multiple doses of HTL0018318 in healthy younger adults and elderly subjects. METHODS: This randomised, double blind, placebo-controlled study was performed, investigating oral doses of 15-35 mg/day HTL0018318 or placebo in 7 cohorts of healthy younger adult (n = 36; 3 cohorts) and elderly (n = 50; 4 cohorts) subjects. Safety, tolerability and pharmacokinetic measurements were performed. Pharmacodynamics were assessed using a battery of neurocognitive tasks and electrophysiological biomarkers of synaptic and cognitive functions. RESULTS: HTL0018318 was generally well-tolerated in multiple doses up to 35 mg/day and were associated with mild or moderate cholinergic adverse events. There were modest increases in blood pressure and pulse rate when compared to placebo-treated subjects, with tendency for the blood pressure increase to attenuate with repeated dosing. There were no clinically significant observations or changes in blood and urine laboratory measures of safety or abnormalities in the ECGs and 24-h Holter assessments. HTL0018318 plasma exposure was dose-proportional over the range 15-35 mg. Maximum plasma concentrations were achieved after 1-2 h. The apparent terminal half-life of HTL0018318 was 16.1 h (± 4.61) in younger adult subjects and 14.3 h (± 2.78) in elderly subjects at steady state. HTL0018318 over the 10 days of treatment had significant effects on tests of short-term (working) memory (n-back) and learning (Milner maze) with moderate to large effect sizes. CONCLUSION: Multiple doses of HTL0018138 showed well-characterised pharmacokinetics and were safe and generally well-tolerated in the dose range studied. Pro-cognitive effects on short-term memory and learning were demonstrated across the dose range. These data provide encouraging data in support of the development of HTL0018138 for cognitive dysfunction in AD and DLB. TRIAL REGISTRATION: Netherlands Trial Register identifier NTR5781 . Registered on 22 March 2016.
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Doença de Alzheimer , Adulto , Idoso , Área Sob a Curva , Cognição , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Países BaixosRESUMO
AIMS: HTL0009936 is a selective M1 muscarinic receptor agonist in development for cognitive dysfunction in Alzheimer's disease. Safety, tolerability and pharmacokinetics and exploratory pharmacodynamic effects of HTL0009936 administered by continuous IV infusion at steady state were investigated in elderly subjects with below average cognitive functioning (BACF). METHODS: Part A was a four-treatment open label sequential study in healthy elderly investigating 10-83 mg HTL0009936 (IV) and a 24 mg HTL0009936 single oral dose. Part B was a five-treatment randomized, double-blind, placebo and physostigmine controlled cross-over study with IV HTL0009936 in elderly subjects with BACF. Pharmacodynamic assessments were performed using neurocognitive and electrophysiological tests. RESULTS: Pharmacokinetics of HTL0009936 showed dose-proportional increases in exposure with a mean half-life of 2.4 hours. HTL0009936 was well-tolerated with transient dose-related adverse events (AEs). Small increases in mean systolic blood pressure of 7.12 mmHg (95% CI [3.99-10.24]) and in diastolic of 5.32 mmHg (95% CI [3.18-7.47]) were noted at the highest dose in part B. Overall, there was suggestive, but no definitive, positive or negative pharmacodynamic effects. Statistically significant effects were observed on P300 with HTL0009936 and adaptive tracking with physostigmine. CONCLUSIONS: HTL0009936 showed well-characterized pharmacokinetics and single doses were safe and generally well-tolerated in healthy elderly subjects. Due to physostigmine tolerability issues and subject burden, the study design was changed and some pharmacodynamic assessments (neurocognitive) were performed at suboptimal drug exposures. Therefore no clear conclusions can be made on pharmacodynamic effects of HTL0009936, although an effect on P300 is suggestive of central target engagement.
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Colinérgicos , Receptores Colinérgicos , Idoso , Área Sob a Curva , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , HumanosRESUMO
INTRODUCTION: The extremely low accident rate for U.S air carriers relative to that of general aviation (â¼1 and â¼60/million flight hours respectively) partly reflects advanced airman certification, more demanding recurrency training and stringent operational regulations. However, whether such skillset/training/regulations translate into improved safety for airline pilots operating in the general aviation environment is unknown and the aim of this study. METHODS: Accidents (1998-2017) involving airline pilots and instrument-rated private pilots (PPL-IFR) operating non-revenue light aircraft were identified from the NTSB accident database. An online survey informed general aviation flight exposure for both pilot cohorts. Statistics used proportion testing and Mann-Whitney U tests. RESULTS: In degraded visibility, 0 and 40% (χ2pâ¯=â¯0.043) of fatal accidents involving airline and PPL-IFR airmen were due to in-flight loss-of-control, respectively. For landing accidents, airline pilots were under-represented for mishaps related to airspeed mismanagement (pâ¯=â¯0.036) relative to PPL-IFR but showed a dis-proportionate count (2X) of ground loss-of-directional control accidents (pâ¯=â¯0.009) the latter likely reflecting a preference for tail-wheel aircraft. The proportion of FAA rule violation-related mishaps by airline pilots was >2X (7 vs. 3%) that for PPL-IFR airmen. Moreover, airline pilots showed a disproportionate (χ2pâ¯=â¯0.021) count of flights below legal minimum altitudes. Not performing an official preflight weather briefing or intentionally operating in instrument conditions without an IFR flight plan represented 43% of airline pilot accidents involving FAA rule infractions. CONCLUSIONS: These findings inform safety deficiencies for: (a) airline pilots, landing/ground operations in tail-wheel aircraft and lack of 14CFR 91 familiarization regulations regarding minimum operating altitudes and (b) PPL-IFR airmen in-flight loss-of-control and poor landing speed management. Practical Applications: For PPL-IFR airmen, training/recurrency should focus on unusual attitude recovery and managing approach speeds. Airline pilots should seek additional instructional time regarding landing tail-wheel aircraft and become familiar with 14CFR 91 rules covering minimum altitudes.
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Acidentes Aeronáuticos/estatística & dados numéricos , Aeronaves/classificação , Aviação/estatística & dados numéricos , Pilotos/educação , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Pilotos/classificação , Fatores de Risco , Estados UnidosRESUMO
Necropsies were performed on five eastern box turtles (Terrapene carolina carolina), found in an area recently subjected to an early-season prescribed fire, to determine whether mortality was burn related. External injuries primarily consisted of burns to exposed extremities and carapacial scutes which ranged from two burned scales to >80% of the shell. Internally, there was no evidence of smoke inhalation, but multiorgan and multifocal inflammation may have contributed to mortality.
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Queimaduras/veterinária , Incêndios , Tartarugas , Animais , Queimaduras/patologia , Feminino , MasculinoRESUMO
Management and control of damage initiation and growth on high-value National Ignition Facility (NIF) optics are critical to its operation. Cone-shaped features are currently being used on the input surfaces to arrest growth of exit surface damage by creating "shadows." Light refracted from the walls of the cones interferes with the incident beam at the exit surface to create an intensified annulus. Significant exit surface damage was observed at the locations of these annuli. Analysis showed that this damage is consistent with a recently reported new mechanism that degrades damage resistance by dispersing damage precursors over the surface upon exposure to UV laser radiation. This has significant implications for the design and operation of high-energy and power laser systems such as the NIF.
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AIMS: HTL0018318 is a selective M1 receptor partial agonist currently under development for the symptomatic treatment of cognitive and behavioural symptoms in Alzheimer's disease and other dementias. We investigated safety, tolerability, pharmacokinetics and exploratory pharmacodynamics (PD) of HTL0018318 following single ascending doses. METHODS: This randomized, double-blind, placebo-controlled study in 40 healthy younger adult and 57 healthy elderly subjects, investigated oral doses of 1-35 mg HTL0018318. Pharmacodynamic assessments were performed using a battery of neurocognitive tasks and electrophysiological measurements. Cerebrospinal fluid concentrations of HTL0018318 and food effects on pharmacokinetics of HTL0018318 were investigated in an open label and partial cross-over design in 14 healthy subjects. RESULTS: Pharmacokinetics of HTL0018318 were well-characterized showing dose proportional increases in exposure from 1-35 mg. Single doses of HTL0018318 were associated with mild dose-related adverse events of low incidence in both younger adult and elderly subjects. The most frequently reported cholinergic AEs included hyperhidrosis and increases in blood pressure up to 10.3 mmHg in younger adults (95% CI [4.2-16.3], 35-mg dose) and up to 11.9 mmHg in elderly subjects (95% CI [4.9-18.9], 15-mg dose). There were no statistically significant effects on cognitive function but the study was not powered to detect small to moderate effect sizes of clinical relevance. CONCLUSION: HTL0018318 showed well-characterized pharmacokinetics and following single doses were generally well tolerated in the dose range studied. These provide encouraging data in support of the development for HTL0018318 for Alzheimer's disease and other dementias.
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Doença de Alzheimer , Adulto , Idoso , Doença de Alzheimer/tratamento farmacológico , Área Sob a Curva , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , HumanosRESUMO
We describe the optimisation of a simplified sample preparation method which permits rapid and direct detection of SARS-CoV-2 RNA within saliva, using reverse-transcription loop-mediated isothermal amplification (RT-LAMP). Treatment of saliva samples prior to RT-LAMP by dilution 1:1 in Mucolyse™, followed by dilution in 10 % (w/v) Chelex© 100 Resin and a 98⯰C heat step for 2â¯min enabled detection of SARS-CoV-2 RNA in positive saliva samples. Using RT-LAMP, SARS-CoV-2 RNA was detected in as little as 05:43â¯min, with no amplification detected in 3097 real-time reverse transcription PCR (rRT-PCR) negative saliva samples from staff tested within a service evaluation study, or for other respiratory pathogens tested (nâ¯=â¯22). Saliva samples can be collected non-invasively, without the need for skilled staff and can be obtained from both healthcare and home settings. Critically, this approach overcomes the requirement for, and validation of, different swabs and the global bottleneck in obtaining access to extraction robots and reagents to enable molecular testing by rRT-PCR. Such testing opens the possibility of public health approaches for effective intervention during the COVID-19 pandemic through regular SARS-CoV-2 testing at a population scale, combined with isolation and contact tracing.
Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , SARS-CoV-2/isolamento & purificação , Saliva/virologia , Manejo de Espécimes/métodos , Humanos , RNA Viral/análiseRESUMO
BACKGROUND: Disease management programmes may improve quality of care, improve health outcomes and potentially reduce total healthcare costs. To date, only one very large population-based study has been undertaken and indicated reductions in hospital admissions > 10%. OBJECTIVE: We sought to confirm the effectiveness of population-based disease management programmes. The objective of this study was to evaluate the relative impact on healthcare utilisation and cost of participants the Costs to Australian Private Insurance - Coaching Health (CAPICHe) trial. DESIGN: Parallel-group randomised controlled trial, intention-to-treat analysis SETTING: Australian population PARTICIPANTS: Forty-four thousand four hundred eighteen individuals (18-90 years of age) with private health insurance and diagnosis of heart failure, chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD), diabetes, or low back pain, with predicted high cost claims for the following 12 months. INTERVENTION: Health coaching for disease management from Bupa Health Dialog, vs Usual Care. MAIN OUTCOME MEASURES: Total cost of claims per member to the private health insurer 1 year post-randomisation for hospital admissions, including same-day, medical and prostheses hospital claims, excluding any maternity costs. Analysis was based on the intent-to-treat population. RESULTS: Estimated total cost 1 year post-randomisation was not significantly different (means: intervention group A$4934; 95% CI A$4823-A$5045 vs control group A$4868; 95% CI A$4680-A$5058; p = 0.524). However, the intervention group had significantly lower same-day admission costs (A$468; 95% CI A$454-A$482 vs A$508; 95% CI A$484-A$533; p = 0.002) and fewer same-day admissions per 1000 person-years (intervention group, 530; 95% CI 508-552 vs control group, 614; 95% CI 571-657; p = 0.002). Subgroup analyses indicated that the intervention group had significantly fewer admissions for patients with COPD and fewer same-day admissions for patients with diabetes. CONCLUSIONS: Chronic disease health coaching was not effective to reduce the total cost after 12 months of follow-up for higher risk individuals with a chronic condition. Statistically significant changes were found with fewer same-day admissions; however, these did not translate into cost savings from a private health insurance perspective.