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The Vestfold Hills are a 400 km2, isolated ice-free oasis in eastern Antarctica featuring large areas with translucent quartz rocks that provide habitat for hypolithic microbial communities underneath. We used high-throughput DNA sequencing of 16S and 18S ribosomal RNA amplicons to characterize bacterial and eukaryotic hypolithic communities across the Vestfold Hills. We found high-level, local heterogeneity in community structure consistent with limited dispersal between hypoliths. Hypolithic communities were dominated by heterotrophic Bacteroidetes (mean bacterial relative read abundance: 56%) as well as Cyanobacteria (35%), with the eukaryote component often dominated by Chlorophyta (43%). Small but significant proportions of the variation in microbial community composition and function were explained by soil salinity (5–7%) and water availability (8–11%), with distinct taxa associated with different salinities and water availabilities. Furthermore, many inferred bacterial metabolic pathways were enriched in hypolithic communities from either dry or high-salinity sites. Vestfold Hills hypolithic habitats are likely to be local refuges for bacterial and eukaryotic diversity. Gradients in soil salinity and water availability across the Vestfold Hills, in addition to the number and diversity of lake types and fjords as potential source populations, may contribute to the observed variation in the extremophile, hypolithic microbial community composition.
Medical surge events require effective coordination between multiple partners. Unfortunately, the information technology (IT) systems currently used for information-sharing by emergency responders and managers in the United States are insufficient to coordinate with health care providers, particularly during large-scale regional incidents. The numerous innovations adopted for the COVID-19 response and continuing advances in IT systems for emergency management and health care information-sharing suggest a more promising future. This article describes: (1) several IT systems and data platforms currently used for information-sharing, operational coordination, patient tracking, and resource-sharing between emergency management and health care providers at the regional level in the US; and (2) barriers and opportunities for using these systems and platforms to improve regional health care information-sharing and coordination during a large-scale medical surge event. The article concludes with a statement about the need for a comprehensive landscape analysis of the component systems in this IT ecosystem.
We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
Does providing information about police shootings influence policing reform preferences? We conducted an online survey experiment in 2021 among approximately 2,600 residents of 10 large US cities. It incorporated original data we collected on police shootings of civilians. After respondents estimated the number of police shootings in their cities in 2020, we randomized subjects into three treatment groups and a control group. Treatments included some form of factual information about the police shootings in respondents’ cities (e.g., the actual total number). Afterward, respondents were asked their opinions about five policing reform proposals. Police shooting statistics did not move policing reform preferences. Support for policing reforms is primarily associated with partisanship and ideology, coupled with race. Our findings illuminate key sources of policing reform preferences among the public and reveal potential limits of information-driven, numeric-based initiatives to influence policing in the US.
Over the last 20 years disasters have increasingly involved children, and pediatric disaster medicine research is growing. However, this research is largely reactive, has not been categorized in terms of the disaster cycle, and the quality of the research is variable. To understand the gaps in current literature and highlight areas for future research, we conducted a scoping review of pediatric disaster medicine literature. This work will help create recommendations for future pediatric disaster medicine research.
Method:
Using a published framework for scoping reviews, we worked with a medical librarian and a multi-institutional team to define the research question, develop eligibility criteria, and to identify a search strategy. We conducted a comprehensive Medline search from 2001-2022, which was distributed to nine reviewers. Each article was independently screened for inclusion by two reviewers. Discrepancies were resolved by a third reviewer.
Inclusion criteria included articles published in English, related to all stages of the disaster cycle, and disaster education, focused on or included pediatric populations; published in academic, peer-reviewed journals, and policies from professional societies.
Results:
967 pediatric disaster medicine articles were imported for screening and 35 duplicates were removed. 932 articles were screened for relevance and 109 were excluded. In 2000, three articles met inclusion criteria and 66 in 2021. We noticed reactive spikes in the number of articles after major disasters. Most articles focused on preparedness and response, with only a few articles on recovery, mitigation, and prevention. Methodology used for most studies was either qualitative or retrospective. Most were single site studies and there were < 10 meta-analyses over the 20 years.
Conclusion:
This scoping review describes the trends in and quality of existing pediatric disaster medicine literature. By identifying the gaps in this body of literature, we can better prioritize future research.
I grew up in Oxford, with parents who were members of the University, but despite being musically very active I never imagined for a moment that I would end up being a musicologist – let alone the Heather Professor of Music. So for the first eighteen years of my life I was dimly aware that there was a Faculty of Music in Oxford, but paid little or no attention to it. As a student at a ‘plate-glass university’ (Sussex) in the 1970s I subscribed to the view that Oxford (and Cambridge) were bastions of tradition and conservatism, and that nothing new or exciting in musical research could be expected from them.
Three pieces of evidence over the next two decades caused me to think that I might have to revise that view. The first was the rather startling discovery, when I was appointed to a post at City University London in 1981, that while City proudly claimed to be one of very few institutions in the world to have a Fairlight digital music synthesiser, the only other one in the UK was in the Oxford Faculty of Music. Really? I thought – reflecting my ignorance of Robert Sherlaw Johnson, who was responsible for that. The second was when a very bright City undergraduate moved to Oxford to do his doctorate under the supervision of Bojan Bujić, and invited me to talk at the Faculty's Research Colloquium series. Do they really want to hear about the psychology of music? I thought. Well they did – and I vividly remember being asked a characteristically acute question by Susan Wollenberg about psychological findings and cultural specificity. And lastly in 2001 I was invited by my Heather Professor predecessor, Reinhard Strohm, to present a paper at his International Symposium ‘Understanding Bach through Science, Art and Criticism’ – an event that emphatically demonstrated (if I still needed to be persuaded) that the Oxford Faculty of Music had an extremely broad and inclusive approach to musical research and enquiry.
If I was blinkered and slow in coming to this realization, the period since I joined the Faculty in 2007 has conclusively shown just how energetic and innovative musical research in Oxford is.
Adverse drug reactions (ADRs) are associated with increased morbidity, mortality, and resource utilization. Drug interactions (DDIs) are among the most common causes of ADRs, and estimates have cited that up to 22% of patients take interacting medications. DDIs are often due to the propensity for agents to induce or inhibit enzymes responsible for the metabolism of concomitantly administered drugs. However, this phenomenon is further complicated by genetic variants of such enzymes. The aim of this study is to quantify and describe potential drug-drug, drug-gene, and drug-drug-gene interactions in a community-based patient population.
Methods
A regional pharmacy with retail outlets in Arkansas provided deidentified prescription data from March 2020 for 4761 individuals. Drug-drug and drug-drug-gene interactions were assessed utilizing the logic incorporated into GenMedPro, a commercially available digital gene-drug interaction software program that incorporates variants of 9 pharmacokinetic (PK) and 2 pharmacodynamic (PD) genes to evaluate DDIs and drug-gene interactions. The data were first assessed for composite drug-drug interaction risk, and each individual was stratified to a risk category using the logic incorporated in GenMedPro. To calculate the frequency of potential drug-gene interactions, genotypes were imputed and allocated to the cohort according to each gene’s frequency in the general population. Potential genotypes were randomly allocated to the population 100 times in a Monte Carlo simulation. Potential drug-drug, gene-drug, or gene-drug-drug interaction risk was characterized as minor, moderate, or major.
Results
Based on prescription data only, the probability of a DDI of any impact (mild, moderate, or major) was 26% [95% CI: 0.248-0.272] in the population. This probability increased to 49.6% [95% CI: 0.484-0.507] when simulated genetic polymorphisms were additionally assessed. When assessing only major impact interactions, there was a 7.8% [95% CI: 0.070-0.085] probability of drug-drug interactions and 10.1% [95% CI: 0.095-0.108] probability with the addition of genetic contributions. The probability of drug-drug-gene interactions of any impact was correlated with the number of prescribed medications, with an approximate probability of 77%, 85%, and 94% in patients prescribed 5, 6, or 7+ medications, respectively. When stratified by specific drug class, antidepressants (19.5%), antiemetics (21.4%), analgesics (16%), antipsychotics (15.6%), and antiparasitics (49.7%) had the highest probability of major drug-drug-gene interaction.
Conclusions
In a community-based population of outpatients, the probability of drug-drug interaction risk increases when genetic polymorphisms are attributed to the population. These data suggest that pharmacogenetic testing may be useful in predicting drug interactions, drug-gene interactions, and severity of interactions when proactively evaluating patient medication profiles.
Migration is an established risk factor for developing a psychotic disorder in countries with a long history of migration. Less is known for countries with only a recent history of migration. This study aimed to determine the risk for developing a psychotic disorder in migrants to the Republic of Ireland.
Methods
We included all presentations of first-episode psychosis over 8.5 years to the DETECT Early Intervention for psychosis service in the Republic of Ireland (573 individuals aged 18–65, of whom 22% were first-generation migrants). Psychotic disorder diagnosis relied on SCID. The at-risk population was calculated using census data, and negative binomial regression was used to estimate incidence rate ratios.
Results
The annual crude incidence rate for a first-episode psychotic disorder in the total cohort was 25.62 per 100000 population at risk. Migrants from Africa had a nearly twofold increased risk for developing a psychotic disorder compared to those born in the Republic of Ireland (IRR = 1.83, 95% CI 1.11–3.02, p = 0.02). In contrast, migrants from certain Asian countries had a reduced risk, specifically those from China, India, Philippines, Pakistan, Malaysia, Bangladesh and Hong Kong (aIRR = 0.36, 95% CI 0.16–0.81, p = 0.01).
Conclusions
Further research into the reasons for this inflated risk in specific migrant groups could produce insights into the aetiology of psychotic disorders. This information should also be used, alongside other data on environmental risk factors that can be determined from census data, to predict the incidence of psychotic disorders and thereby resource services appropriately.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
Design:
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
Methods:
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Results:
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
Conclusions:
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
ABSTRACT IMPACT: This work sheds diagnostic insight on patients with idiopathic rare disease and has the potential to further their care and treatment as a result. OBJECTIVES/GOALS: Correct diagnosis is imperative to treating patients with idiopathic, suspected genetic conditions, yet sequencing approaches leave up to 70% of these patients undiagnosed. We sought to improve diagnosis rates for a cohort patients referred for sequencing by characterizing deleterious variants within the 5’UTR. METHODS/STUDY POPULATION: We retrospectively analyzed whole exome sequencing (WES) data from 472 unsolved rare disease patients within the Mayo Clinic Center for Individualized Medicine to identify variants within the 5’UTR that affect the presence of upstream open reading frames (uORFs). uORFs are short regions (typically 30bp - 600bp) that typically influence downstream gene translation by sequestering ribosomes. We specifically searched for variants with the potential to disrupt existing uORFs or introduce new uORFs within the 5’UTR, and developed a pipeline to annotate these variants with information including GnomAD allele frequency and gene loss of function intolerance (pLI) score. To aid in variant interpretation, we applied two deep learning tools to predict variant impacts on transcript ribosome load (TITER and FramePool). RESULTS/ANTICIPATED RESULTS: Our pipeline identified a median of 21 variants per patient that were predicted to have a deleterious impact on the translational efficiency of protein coding transcripts, primarily by introducing new start codons within the 5’UTR or by altering the Kozak consensus of existing start codons. A median of 10 of these variants occur upstream of haploinsufficient genes with an existing disease association. We also identified a subset of variants that are predicted to introduce translationally active N-terminal extensions to protein coding transcripts, with the potential to disrupt protein localization and processing. DISCUSSION/SIGNIFICANCE OF FINDINGS: This work demonstrates that analysis of 5’UTR variants can be incorporated into existing WES pipelines, and identifies a group of variants with potential significance to patient disease. Further experimental evidence is necessary to ascertain the pathogenicity of these variants.
Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
Members of historically underrepresented groups—women, African Americans, Latinos, and workers—are serving in American legislatures in increasing numbers. However, legislators wield substantially greater power in the lawmaking process when they hold leadership positions. Incorporation of these groups into leadership positions could indicate fuller political representation, but scholars to date have not assessed how well these groups are represented in leadership. We analyze original data describing the backgrounds of approximately 2,200 leaders in 30 states between 2003 and 2014. The data show that, on average across states, members of these groups are as well represented in state legislative leadership positions as they are in rank-and-file membership, but there is substantial variation across states and across parties. We then ask what factors might explain this variation and explore institutional characteristics, like the number of leadership positions or leader selection methods. The results show that legislative chambers with a higher number of leadership posts tend to have more women in leadership, and that selection through elections is associated with decreased African American presence in leadership. The findings have implications for minority incorporation and influence in American politics.
The nineteenth century saw a number of significant changes in European musical culture, including changes in the size and nature of the orchestra and the rise of the modern conductor. The coordination and musical leadership of orchestras has taken a variety of forms historically, but from around the middle of the nineteenth century silent conducting gradually began to supplant other forms of time keeping and instrumental leadership in opera and concert orchestras. Little or no empirical work has attempted to investigate the musical, social and perceptual consequences of this development, largely due to the technical challenges that must be addressed. This article describes the development and implementation of innovative digital methods to provide a detailed and multifaceted picture of a large ensemble in action, investigating the consequences of different distributions of individual musical agency for: 1) musicians’ playing experiences; 2) ensemble coordination and expressive timing; and 3) listeners’ evaluations. These methods include a polling application, implemented on participants’ smartphones, to provide fast-turnaround feedback from orchestral musicians about their experiences of playing under different conditions; and the use of digital methods to analyse acoustical data from the individual instruments of an orchestral string section, to facilitate a quantitative analysis of orchestral togetherness. Analyses of the experiential, quantitative and listener data from a preliminary study with an orchestra of musicians from the Royal Academy of Music, London, are presented, together with a discussion of the insights that these methods provide. The article concludes by considering the prospects of these methods for investigating nineteenth-century rehearsal and performance practices.
Early intervention in psychosis is a complex intervention, usually delivered in a specialist stand-alone setting, which aims to improve outcomes for people with psychosis. Previous studies have been criticised because the control used did not accurately reflect actual practice.
Aims
To evaluate the cost-effectiveness of early intervention by estimating the incremental net benefit (INB) of an early-intervention programme, delivered in a real-world setting. INB measures the difference in monetary terms between alternative interventions.
Method
Two contemporaneous incidence-based cohorts presenting with first-episode psychosis, aged 18–65 years, were compared. Costs and outcomes were measured over 1 year. The main outcome was avoidance of a relapse that required admission to hospital or home-based treatment.
Results
From the health sector perspective, the probability that early intervention was cost-effective was 0.77. The INB was €2465 per person (95% CI − €4418 to €9347) when society placed a value of €6000, the cost of an in-patient relapse, on preventing a relapse requiring admission or home care. Following adjustment, the probability that early intervention was cost-effective was 1, and the INB to the health sector was €3105 per person (95% CI −€8453 to €14 663). From a societal perspective, the adjusted probability that early intervention was cost-effective was 1, and the INB was €19 928 per person (95% CI − €2075 to €41 931).
Conclusions
Early intervention has a modest INB from the health sector perspective and a large INB from the societal perspective. The perspective chosen is critical when presenting results of an economic evaluation of a complex intervention.
A 141m ice core was recovered from Combatant Col (51.385° N, 125.258° W; 3000ma.s.l.), Mount Waddington, Coast Mountains, British Columbia, Canada. Records of black carbon, dust, lead and water stable isotopes demonstrate that unambiguous seasonality is preserved throughout the core, despite summer surface snowmelt and temperate ice. High accumulation rates at the site (>4 m ice eq. a-1) limit modification of annual stratigraphy by percolation of surface meltwater. The ice-core record spans the period 1973–2010. An annually averaged time series of lead concentrations from the core correlates well with historical records of lead emission from North America, and with ice-core records of lead from the Greenland ice sheet. The depth-age scale for the ice core provides sufficient constraint on the vertical strain to allow estimation of the age of the ice at bedrock. Total ice thickness at Combatant Col is ~250 m; an ice core to bedrock would likely contain ice in excess of 200 years in age. Accumulation at Combatant Col is significantly correlated with both regional precipitation and large-scale geopotential height anomalies.
The aim of the study is to determine the performance of low-dose ketamine (LDK) as an analgesic for acute pain management in adult patients in the emergency department (ED).
Methods
We systematically reviewed electronic databases, grey literature, conference abstracts, and clinical trial registries. Two independent reviewers identified eligible studies. These selections were subsequently reviewed by one reviewer who identified the final eligible studies, using refined inclusion and exclusion criteria. Our outcome measures included the analgesic effect of LDK, need for rescue analgesia, and neuropsychological adverse events secondary to LDK use. We assessed inter-rater agreement using kappa statistics and proposed a treatment recommendation using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) software. Heterogeneity among studies precluded meta-analysis.
Results
Our electronic search identified 1,408 records; 44 were selected for full evaluation (kappa=0.70), and 8 were included after the final review. All six randomized controlled trials and two observational studies were set in the ED where LDK was administered to adult patients ( >18 years old) exclusively for pain management. All studies had an overall low risk of bias. There was extensive variation in the dose and route of LDK used (0.1-0.7 mg/kg SC/IV/IM), administration protocols, and use of adjunct analgesia. Overall, most studies reported a significant analgesic effect of LDK with occasional need for rescue analgesia and mild-to-moderate adverse events (dizziness, dysphoria, and confusion).
Conclusion
There are moderate to low quality data supporting LDK as an alternative analgesic in the ED with the potential for minimal requirement of rescue analgesia and self-limited neuropsychological adverse events.
Field experiments were conducted in 1999 and 2000 at the Rice Research and Extension Center at Stuttgart, AR, on a DeWitt silt loam and at the Pine Tree Branch Experiment Station near Colt, AR, on a Calloway silt loam to evaluate the tolerance of 14 rice cultivars and four experimental cultivar lines to clomazone at 0.34 and 0.67 kg ai/ha applied preemergence. Early-season chlorosis 14 days after emergence (DAE) ranged from 1 to 21% in 1999 and 3 to 40% in 2000 when averaged over herbicide rate. The experimental cultivar line RU961096 was slightly more susceptible to clomazone than other cultivars and lines. However, RU9701041 was more tolerant to clomazone at 0.67 kg/ha 14 DAE than other cultivars and lines. By 28 DAE, all cultivars had <13% chlorosis in 1999 and <8% in 2000. The experimental cultivar line RU9601096 and cultivar Koshihikari did not recover as quickly as the other 16 cultivars and cultivar lines. Early-season chlorosis had no effect on days to 50% heading or yield for any of the cultivars evaluated.
Ground ivy is a stoloniferous, perennial weed that persists in lawn turf. With the widespread use of 2,4-D on turf sites, the development of 2,4-D–tolerant ground ivy is a possibility. Ground ivy populations showed a highly variable response to foliar 2,4-D application. Ground ivy from Nebraska (NE) was tolerant to 2,4-D, whereas Ohio (OH) ground ivy was susceptible. The 2,4-D–susceptible OH population absorbed 37% more foliar-applied 14C–2,4-D than the 2,4-D–tolerant NE population. Although OH and NE populations total translocation of applied 14C was similar and averaged 5%, the OH population translocated 42% more toward the apical meristem of the primary stolon than the NE population, primarily because of the OH population's higher 14C–2,4-D absorption. The variation in response to 2,4-D found between these two populations occurred after exposure of roots to 2,4-D, but the effect was less pronounced. These results suggest that the difference in foliar uptake may partially contribute to differences in response to 2,4-D between these two populations. Likewise, differences in acropetal translocation may contribute to the differential sensitivity of 2,4-D–tolerant and –susceptible ground ivy populations.
Ground ivy is an invasive, perennial, broadleaf weed common in turf sites. A recent survey of lawn care professionals suggests ground ivy populations respond differently to herbicides. Our study was conducted to determine the variation in response among and within ground ivy populations to 2,4-D or triclopyr application. Ground ivy populations were sampled from nine sites in the United States and Canada. Leaf width, petiole length, and internode length varied by population by as much as 31, 36, and 45%, respectively. In a greenhouse study, applying 4.5 kg/ha 2,4-D or 0.9 kg/ha triclopyr to all populations resulted in a phytotoxic response that varied according to population by as much as 47% for 2,4-D and 31% for triclopyr. Random-amplified polymorphic DNA analysis identified 52 genotypes in the nine populations, and these genotypes varied in response to 2,4-D application in some populations. Difficulty in control of ground ivy with 2,4-D or triclopyr may be because of the presence of ecotypes and biotypes.