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Extreme weather has a direct and significant impact on buildings and infrastructure, resulting in billions of dollars of damage each year. This problem continues to grow as climate patterns change and buildings are exposed to new and different hazards than what they were designed to withstand. In order to better plan for the long-range sustainment, restoration, modernization, and eventual recapitalization of these buildings, organizations with large building portfolios, such as the U.S. Department of Defense (DoD), must have an awareness of the risks that these extreme weather events present. This research aimed to develop an approach to estimate condition loss and reduction in service life for the components of a building due to extreme weather hazards, to understand the risks that may be present in certain buildings and building systems. To achieve this objective, a damage association matrix was developed that categorizes climate hazards, the damage modes that they produce, and the individual component types impacted. This damage matrix formally links state-of-the-art climate model output, which provides projections of the probability of various climate hazards with a damage effects model that quantifies the consequence on component-level condition and service life. This method is applied to an actual portfolio of buildings in a particular geographic location and with a pre-defined component inventory that comprises the building. This approach can be aggregated to the system-, facility-, and site-level thus helping support billions of dollars in recapitalization decisions related to restoration/modernization of facilities.

Adaptation to extreme environments often involves the evolution of dramatic physiological changes. To better understand how organisms evolve these complex phenotypic changes, the repeatability and predictability of evolution, and possible constraints on adapting to an extreme environment, it is important to understand how adaptive variation has evolved. Poeciliid fishes represent a particularly fruitful study system for investigations of adaptation to extreme environments due to their repeated colonization of toxic hydrogen sulfide-rich springs across multiple species within the clade. Previous investigations have highlighted changes in the physiology and gene expression in specific species that are thought to facilitate adaptation to hydrogen sulfide-rich springs. However, the presence of adaptive nucleotide variation in coding and regulatory regions and the degree to which convergent evolution has shaped the genomic regions underpinning sulfide tolerance across taxa are unknown. By sampling across seven independent lineages in which nonsulfidic lineages have colonized and adapted to sulfide springs, we reveal signatures of shared evolutionary rate shifts across the genome. We found evidence of genes, promoters, and putative enhancer regions associated with both increased and decreased convergent evolutionary rate shifts in hydrogen sulfide-adapted lineages. Our analysis highlights convergent evolutionary rate shifts in sulfidic lineages associated with the modulation of endogenous hydrogen sulfide production and hydrogen sulfide detoxification. We also found that regions with shifted evolutionary rates in sulfide spring fishes more often exhibited convergent shifts in either the coding region or the regulatory sequence of a given gene, rather than both.

Abstract Background People with end-of-life chronic obstructive pulmonary disease (COPD) experience debilitating physical limitations, with a high mortality rate. Our research has shown health system design and delivery leads to inequitable outcomes. Enabling people with end-of-life COPD, their support people, and health professionals to partner in setting the agenda for resource allocation may inform health service improvement. Design Qualitative methodology utilising focus groups including patients, family, friends, informal support people, health care workers and professionals. Methods The analysis, utilising critical theory and Actor-Network theory, positioned people with severe COPD, their support people and health professionals as experts in end-of-life care. Analyses triangulated these perspectives, and were reviewed by the research investigators and an expert reference group. Results Participants (n=74) in seven focus groups reported their experiences of inequity within the healthcare system. Equity was an overarching phenomenon identified by participants, with three specific themes being described: policy design, system design, and service design. Conclusion Experiences of patients, their support people and health professionals as experts in end-of-life COPD care can inform health systems and health service design to address current inequities in funding and delivery of care for end-of-life COPD.

OBJECTIVE: Perianal Crohns disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in Complement Factor B (CFB). DESIGN: Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed. Serological and clinical variables were analysed by regression analyses. Risk allele of rs4151651 was introduced into human CFB plasmid by site-directed mutagenesis. Binding of recombinant G252 or S252 CFB to C3b and its cleavage was determined in cell-free assays. Macrophage phagocytosis in presence of recombinant CFB or serum from CFB risk, or protective CD or healthy subjects was assessed by flow cytometry. RESULTS: Perianal complications were associated with colonic involvement, OmpC and ASCA serology, and serology quartile sum score. We identified a genetic association for pCD (rs4151651), a non-synonymous SNP (G252S) in CFB, in all three cohorts. Recombinant S252 CFB had reduced binding to C3b, its cleavage was impaired, and complement-driven phagocytosis and cytokine secretion were reduced compared with G252 CFB. Serine 252 generates a de novo glycosylation site in CFB. Serum from homozygous risk patients displayed significantly decreased macrophage phagocytosis compared with non-risk serum. CONCLUSION: pCD-associated rs4151651 in CFB is a loss-of-function mutation that impairs its cleavage, activation of alternative complement pathway, and pathogen phagocytosis thus implicating the alternative complement pathway and CFB in pCD aetiology.

Abstract Background Head injuries are the most common cause of death in some motorized vehicles for which helmet use can significantly decrease the risk. Our objective was to determine rural adolescents’ attitudes regarding helmets and their use while riding ATVs, motorcycles and dirt bikes. Methods A convenience sample of 2022 Iowa FFA (formerly Future Farmers of America) Leadership Conference attendees were surveyed. After compilation, data were imported into the statistical program, R ( https://www.R-project.org/ ). Descriptive statistics, contingency table, logistic regression and non-parametric alternatives to ANOVA analyses were performed. Results 1331 adolescents (13–18 years) participated. One half lived on a farm, 21% lived in the country/not on a farm and 28% were from towns. Nearly two-thirds (65%) owned an ATV with 77% of all having ridden one in the past year. Farm residents had the highest ATV ownership (78%) and having ridden (80%) proportions, both p

Abstract This study was performed to determine whether prolonged endurance running results in acute endothelial dysfunction and wave‐reflection, as endothelial dysfunction and arterial stiffness are cardiovascular risk factors. Vascular function (conduit artery/macrovascular and resistance artery/microvascular) was assessed in 11 experienced runners (8 males, 3 females) before, during and after a 50 km ultramarathon. Blood pressure (BP), heart rate (HR), wave reflection, augmentation index (AIx) and AIx corrected for HR (AIx75) were taken at all time points—Baseline (BL), following 10, 20, 30 and 40 km, 1 h post‐completion (1HP) and 24 h post‐completion (24HP). Flow‐mediated dilatation (FMD) and inflammatory biomarkers were examined at BL, 1HP and 24HP. Reactive hyperaemia area under the curve (AUC) and shear rate AUC to peak dilatation were lower (∼75%) at 1HP compared with BL (P

Abstract DPANN archaea are a diverse group of microorganisms characterised by small cells and reduced genomes. To date, all cultivated DPANN archaea are ectosymbionts that require direct cell contact with an archaeal host species for growth and survival. However, these interactions and their impact on the host species are poorly understood. Here, we show that a DPANN archaeon (Candidatus Nanohaloarchaeum antarcticus) engages in parasitic interactions with its host (Halorubrum lacusprofundi) that result in host cell lysis. During these interactions, the nanohaloarchaeon appears to enter, or be engulfed by, the host cell. Our results provide experimental evidence for a predatory-like lifestyle of an archaeon, suggesting that at least some DPANN archaea may have roles in controlling host populations and their ecology.

Abstract Objective Neurofilament heavy‐chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk. Methods Genetic data of 11,130 people with ALS and 7,416 controls from the literature and Project MinE were analysed. We performed meta‐analyses of published case–control studies reporting NEFH variants, and variant analysis of NEFH in Project MinE whole‐genome sequencing data. Results Fixed‐effects meta‐analysis found that rare (MAF

Alphaviruses are arthropod-borne, single-stranded positive-sense RNA viruses that are recognized as rapidly emerging pathogens. Despite being exquisitely sensitive to the effects of the innate immune response alphaviruses can readily replicate, disseminate, and induce pathogenesis in immunologically competent hosts. Nonetheless, how alphaviruses evade the induction of an innate immune response prior to viral gene expression, or in non-permissive infections, is unknown. Previously we reported the identification of a novel host/pathogen interaction between the viral Capsid (CP) protein and the host IRAK1 protein. The CP/IRAK1 interaction was determined to negatively impact IRAK1-dependent PAMP detection in vitro, however, the precise importance of the CP/IRAK1 interaction to alphaviral infection remained unknown. Here we detail the identification of the CP/IRAK1 interaction determinants of the Sindbis virus (SINV) CP protein and examine the importance of the interaction to alphaviral infection and pathogenesis in vivo using an interaction deficient mutant of the model neurotropic strain of SINV. Importantly, these interaction determinants are highly conserved across multiple Old-World alphaviruses, including Ross River virus (RRV), Mayaro virus (MAYV), Chikungunya virus (CHIKV), and Semliki Forest virus (SFV). In the absence of a functional CP/IRAK1 interaction, SINV replication is significantly restricted and fails to disseminate from the primary site of inoculation due to the induction of a robust type-I Interferon response. Altogether these data indicate that the evasion of IRAK1-dependent signalling is critical to overcoming the host innate immune response and the in vivo data presented here demonstrate the importance of the CP/IRAK1 interaction to neurovirulence and pathogenesis.

Abstract The initial delivery of small‐scale magnetic devices such as microrobots is a key, but often overlooked, aspect for their use in clinical applications. The deployment of these devices within the dynamic environment of the human body presents significant challenges due to their dispersion caused by circulatory flows. Here, a method is introduced to effectively deliver a swarm of magnetic nanoparticles in fluidic flows. This approach integrates a magnetically navigated robotic microcatheter equipped with a reservoir for storing the magnetic nanoparticles. The microfluidic flow within the reservoir facilitates the injection of magnetic nanoparticles into the fluid stream, and a magnetic field gradient guides the swarm through the oscillatory flow to a target site. The microcatheter and reservoir are engineered to enable magnetic steering and injection of the magnetic nanoparticles. To demonstrate this approach, experiments are conducted utilizing a spinal cord phantom simulating intrathecal catheter delivery for applications in the central nervous system. These results demonstrate that the proposed microcatheter successfully concentrates nanoparticles near the desired location through the precise manipulation of magnetic field gradients, offering a promising solution for the controlled deployment of untethered magnetic micro‐/nanodevices within the complex physiological circulatory systems of the human body.

PurposeThe purpose of this survey study is to compare the experiences of programs and applicants in the MedPhys Match (MPM) in the 2020-21 match cycle with experiences reported from previous match cycles. The 2020-21 match cycle was unique in that recruitment and interviewing were almost exclusively virtual during the COVID-19 pandemic.MethodsA survey was sent to all applicants and programs registered for the 2020-21 MPM. Survey questions asked about the pre-interview screening, interview, ranking, and post-match stages of the residency match process. Survey data were analyzed using graphical methods and spreadsheet tools.ResultsAdvantages and disadvantages to the virtual interviewing experience were reported by applicants and program directors (PDs). The advantages included reduced cost and greater scheduling flexibility with fewer scheduling conflicts, allowing applicants to consider more programs. These advantages greatly outweighed the disadvantages such as the inability to meet faculty/staff and current residents in person and gauge the feel of the program. PDs recognized the advantages of minimal costs and time savings for applicants. Programs reported it was difficult to convey workplace culture and the physical environment and to gauge personality and interpersonal skills of the applicants.ConclusionThe virtual interviewing environment for residency recruitment in medical physics is strongly preferred by applicants over required in-person interviews. The advantages identified by applicants outweigh the disadvantages, allowing applicants to feel confident in their ranking decisions and overall satisfied with their match results. PDs acknowledge the greater equity of access to interviews for applicants in the virtual environment, however, they are overall less satisfied with their ability to showcase their program's strengths and to assess the personality of applicants. Caution is urged when considering a hybrid interview model to ensure fair assessments that do not depend on whether an applicant chooses to accept an optional in-person interview or site visit.

Abstract Digital health innovation is expected to transform healthcare, but it also generates ethical and societal concerns, such as privacy risks, and biases that can compound existing health inequalities. While such concerns are widely recognized, existing regulatory principles, oversight methods and ethical frameworks seem out of sync with digital health innovation. New governance and innovation best practices are thus needed to bring such principles to bear with the reality of business, innovation, and regulation. To grant practical insight into best practices for responsible digital health innovation, we conducted a qualitative study based on an interactive engagement methodology. We engaged key stakeholders (n = 46) operating at the translational frontier of digital health. This approach allowed us to identify three clusters of governance and innovation best practices in digital health innovation: i) inclusive co-creation, ii) responsive regulation, and iii) value-driven innovation. Our study shows that realizing responsible digital health requires diverse stakeholders’ commitment to adapt innovation and regulation practices, embracing co-creation as the default modus operandi for digital health development. We describe these collaborative practices and show how they can ensure that innovation is neither slowed by overregulation, nor leads to unethical outcomes.

The perioperative maintenance of a patient’s core temperature is a challenge during burn care. While patient warming devices are sometimes used to prevent intraoperative hypothermia, raising the ambient temperature of the theatre is the most common practice. Theatre temperature can impact on the performance and comfort of surgery staff but standards for theatre temperatures in burn care are poorly defined. Therefore, in this study we investigated the current, global, clinical practices in burn care with respect to the ambient temperature of theatres that are used to treat severe burn injuries. An internet-based, descriptive, QualtricsXM survey was distributed electronically to 81 burn professionals to identify the temperatures at which the surgical teams operate on severe burn injuries. The survey was completed by 33 participants from 15 countries and revealed that there is a wide range of temperatures (24–45°C) at which burn injuries are treated. The prevention of hypothermia was the clinical justification most reported for those theatre temperatures. Temperatures between 26 and 30°C appear to be most comfortable for the staff. One respondent mentioned that surgeries are often limited to 5 h to avoid hypothermia in patients, however, others noted surgery durations of up to 8–12 h in raised temperatures, which may impact the physiology and performance of the team, potentially impacting the safety of the patients. The adoption of an optimal theatre temperature to address the surgical team’s comfort levels, their performance, and patient hypothermia, may improve outcomes in cases of severe burn injury.