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Bis-tridentate (1,2,3-triazol-4-yl)picolinamide (tzpa) was used to form Tb(iii) double- and triple-stranded di-metallic helicates in solution, where changes in the absorption and the Tb(iii) emission were used to monitor the formation of these supramolecular systems.

Introduction: Accurate and timely medication information is crucial for health professionals working in a hospital environment. This article focuses on the findings of a medication information resources survey undertaken in a northern Australian health service. Objectives: To examine health professionals’ usage and satisfaction of medication information resources available to them. Methods: An online survey of staff was undertaken in May 2021. Results: There were 206 responses to the survey. Eighty-eight percent of respondents were either nurses, pharmacists or doctors. The four most popular resources were: Australian Medicines Handbook, Therapeutic Guidelines, MIMS Online and Australian Injectable Drugs Handbook. Fifty-three percent of respondents use the resources daily or more than once per day. Doctors are more likely to use the app version and the Health Library’s website is where the majority access the resource from. Eighty-one percent felt that it was extremely or moderately easy to access resources. Discussion: Responses from the open-ended question indicate that there is a lack of awareness of a number of resources which supports the need for strategic promotion and education. Conclusion: The results of this study have shown that health libraries subscribing to key medication information resources supports patient care and best practice.

Efforts to improve quality in healthcare have arisen from the recognition that the quality of care delivered and resulting outcomes are highly variable. Performance benchmarking using high-quality data to compare risk-adjusted outcomes between hospitals and surgeons has been widely adopted as one means for addressing this problem. In this article we discuss the history, current state, methodologies, and potential pitfalls of benchmarking efforts to improve quality of healthcare in the United States.

During the early stages of the UK 2021-2022 H5N1 high-pathogenicity avian influenza virus (HPAIV) epizootic in commercial poultry, 12 infected premises (IPs) were confirmed by four real-time reverse-transcription–polymerase chain reaction (RRT)-PCRs, which identified the viral subtype and pathotype. An assessment was undertaken to evaluate whether a large sample throughput would challenge laboratory capacity during an exceptionally large epizootic; hence, assay performance across our test portfolio was investigated. Statistical analysis of RRT-PCR swab testing supported it to be focused on a three-test approach, featuring the matrix (M)-gene, H5 HPAIV-specific (H5-HP) and N1 RRT-PCRs, which was successfully assessed at 29 subsequent commercial IPs. The absence of nucleotide mismatches in the primer/probe binding regions for the M-gene and limited mismatches for the H5-HP RRT-PCR underlined their high sensitivity. Although less sensitive, the N1 RRT-PCR remained effective at flock level. The analyses also guided successful surveillance testing of apparently healthy commercial ducks from at-risk premises, with pools of five oropharyngeal swabs tested by the H5-HP RRT-PCR to exclude evidence of infection. Serological testing at anseriform H5N1 HPAIV outbreaks, together with quantitative comparisons of oropharyngeal and cloacal shedding, provided epidemiological information concerning the chronology of initial H5N1 HPAIV incursion and onward spread within an IP.

Funding: Natural Environment Research Council. Grant Number: NE/T006269/1. Uncertainty in the response of clouds to global warming remains a significant barrier to reducing uncertainty in climate sensitivity. A key question is the extent to which the dynamic component—that which is due to changes in circulation rather than changes in the thermodynamic properties of clouds—contributes to the total cloud feedback. Here, simulations with a range of cloud-resolving models are analyzed to quantify the impact of circulation changes on tropical cloud feedbacks. The dynamic component of the cloud feedback is substantial for some models and is controlled both by sea surface temperature (SST) induced changes in circulation and nonlinearity in the climatological relationship between clouds and circulation. We find notable inter-model differences in the extent to which ascending regions narrow or expand in response to a change in SST, which we link to differences in the longwave and shortwave dynamic components across models. The diversity of changes in ascent area is coupled to intermodel differences in non-radiative diabatic heating in ascending regions. Publisher PDF

The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients.Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality.We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications.A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P0.0001).Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.

Governments often make public announcements that call into question firms' misuse of market power. Yet little is known about how firms respond to them. We study gasoline retailers' price responses to antitrust announcements shaming them for price gouging during the COVID-19 pandemic. We identify price effects using a high-frequency event-study leveraging unique real-time station-level price data and well-identified, discrete antitrust announcements. We find evidence of announcement effects that depend on firms' preannouncement margins and hence exposure to being publicly shamed. Public statements by antitrust questioning firms' misuse of market power can indeed contain signals that affect equilibrium outcomes.

Workhorse economic models used for studying the market impacts of search frictions assume constant search costs: individuals pay the same cost to obtain price information each time they search. This paper provides evidence on a new form of search costs: start-up costs. Exploiting a natural experiment in retail gasoline, we document how a temporary, large exogenous shock to consumers’ search incentives leads to a substantial, permanent increase in price search. A standard search model fails to explain such history dependence in search, while it follows directly from a model with a one-time up-front cost to start searching. (JEL D83, L13, L81)

We use a field experiment to study price discrimination in a market with price posting and negotiation. Motivated by concerns that low-income consumers do poorly in markets with privately negotiated prices, we built a call center staffed with actors armed with bargaining scripts to reveal negotiated prices and their determinants. Our actors implement sequential bargaining games under incomplete information in the field. By experimentally manipulating how information is revealed, we generate sequences of price offers that allow us to identify price discrimination in negotiations based on retailer perceptions of consumers’ search and switching costs. We also document differences in price distributions between entrants and incumbents, reflecting differences in captivity of their respective consumer bases. Finally, we show that higher prices paid by lower-income subsidy recipients in our market is not due to discriminatory targeting; they can be explained by variation in consumer willingness and ability to search and bargain.

Background and aimsBariatric, also termed metabolic, surgery is an increasingly common treatment for severe and complex obesity. It decreases macronutrient intake, influences nutrient absorption and modifies gastrointestinal physiology with the aim of reducing adiposity, improving metabolism and reducing disease risk. Bariatric surgery has been shown to result in micronutrient deficiencies. Whether it results in deficiencies of essential fatty acids (EFAs) and their bioactive polyunsaturated fatty acid (PUFA) derivatives is not clear. The aim of this systematic review is to identify whether there are effects of bariatric surgery on the blood levels of EFAs and other PUFAs.MethodsA database search was conducted up to November 2020 using Medline, Embase and Cinahl databases, using relevant search terms identified by a PICO protocol. Only human studies reporting on PUFAs in a blood pool, published in the English language and available in full text were included. The Cochrane tool for assessing risk of bias was used and data were extracted.ResultsFifteen papers from fourteen studies with relevant data were identified for inclusion. Studies differed according to surgical intervention, duration, measured timepoints, sample size and PUFAs reported. Both increases and decreases in selected PUFAs were reported in different studies. For the EFAs linoleic acid and α-linolenic acid and for the longer-chain omega-3 PUFA eicosapentaenoic acid, bariatric surgery is associated with a transient decline in status (to about 6 months post-surgery) with a later return to pre-surgery levels. All studies had some risk of bias and most studies were of small size.ConclusionThere is a decrease in blood levels of both EFAs and of eicosapentaenoic acid in the months following bariatric surgery. This may partly counter the desired effects of the surgery on blood lipids, insulin sensitivity and inflammation. Nutritional strategies (e.g. use of modified formulas or of supplements) may be able to correct the decrease in those PUFAs. Nevertheless, the observed decrease in PUFAs is transient.

We have developed a high-throughput computational method to predict the superconducting transition temperature in stable hexagonal M$$_2$$ 2 AX phases, and applied it to all the known possible choices for M (M: Sc, Ti, V, Cr, Mn, Fe, Y, Zr, Nb, Mo, Lu, Hf and Ta). We combine this with the best candidates for A (A: Al, Cu, Ge and Sn ) and X (X: C and N) from our previous work, and predict T$$_c$$ c for 60 M$$_2$$ 2 AX-phase materials, 53 of which have never been studied before. From all of these, we identify Cr$$_2$$ 2 AlN as the best candidate for the highest T$$_c$$ c , and confirm its high T$$_c$$ c with more detailed density functional theory electron-phonon coupling calculations. Our detailed calculations predict $$T_c$$ T c = 14.8 K for Cr$$_2$$ 2 AlN, which is significantly higher than any $$T_c$$ T c value known or predicted for any material in the M$$_2$$ 2 AX family to date.

“The difference between a mere chronological compilation of facts and a narration, which contextualizes events and creates a logical cause-and-effect link between them, is what distinguishes the chronicler from the historian” (Raines, p. 32, in Kolditz and Koller, The Byzantine-Ottoman Transition in Venetian Chronicles 2018 [cited under Section Seven: Venice and the Veneto: From John the Deacon to Enrico Dandolo: Studies]). This bibliography includes scholarship on chronicles, histories, and annals from 8th-century Paul the Deacon, author of the History of the Lombards, to the threshold of early Renaissance or humanistic historiography in the mid-Trecento. Medieval Italian writers on history came from many walks of life: Bernardo Maragone (b. c. 1109–d. 1188) the Pisan judge; Caffaro (b. 1080/81–d. 1166), a Genoese nobleman and communal consul and official; Rolandino (b. 1200–d. 1276), a Paduan notary; Florentine merchant Giovanni Villani (b. c. 1275–d. 1348); Pisan poets; Anonimo Romano, a 14th-century layman trained in medicine; Genoese archbishop Jacopo da Varagine (b. c. 1228–d. 1298); 11th-century Milanese diocesan clergy Arnulf and Landulf Senior; and Paduan Albertino Mussato (b. 1261–d. 1329), a notary, poet laureate, diplomat, proto-humanist, and historiographer. Most significant chronicles have known authors, details of whose lives are often obscure, though the most lauded Trecento Roman chronicler is simply known as Anonimo. They wrote in both Latin and the vernacular. Their efforts produced a huge body of medieval literature: there are said to be extant some 1,000 chronicles from Venice alone, the vast majority unpublished and unstudied. Historical works range in scope from universal histories to poems on single battles or other events of note. Like any literary field, medieval historiography is informed by scholarly trends, from the collecting, editing, and publishing of texts beginning in the eighteenth century to the much more recent challenges of postmodern critiques and opportunities for electronic publication. Section One and Section Two introduce the fields of medieval European and Italian historiography, respectively. Contemporary analytical interests are represented in Section Three, Section Four, and Section Five on literary aspects of chronicles, the “Other” in texts, and the ways in which urban authors presented (often mythological) local urban or communal origins. Each of these subjects is well served by modern scholarship. Part Three presents ten sections, four on regions or cities and their chroniclers: Venice, Florence, non-Florentine Tuscany, and southern Italy and Sicily under the Normans and Hohenstaufens. The remaining six sections feature specific authors: Paul the Deacon (b. c. 730–d. 799) and his Lombards, Caffaro and the Genoese, the Florentine Villanis, the 11th-century Norman monk of Montecassino Geoffrey Malaterra, the Franciscan Salimbene de Adam (b. 1221–d. c. 1289), and Anonimo Romano. Admittedly, for some readers this will be an unsatisfying list, especially as it omits Milan, Lombardy, and other northern Italian regions. Criteria for a work’s presence include recognized relevance, importance, recent publication, and accessibility.

We have developed a high-throughput computational method to predict the superconducting transition temperature in stable hexagonal M2AX phases and applied it to all the known possible choices for M (M: Sc, Ti, V, Cr, Mn, Fe, Y, Zr, Nb, Mo, Lu, Hf and Ta). We combine this with the best candidates for A (A: Al, Cu, Ge and Sn) and X (X: C and N) from our previous work, and predict Tc for 60 M2AX-phase materials, 53 of which have never been studied before. From all of these, we identify Cr2AlN as the best candidate for the highest Tc, and confirm its high Tc with more detailed density functional theory electron-phonon coupling calculations. Our detailed calculations predict Tc = 14.8 K for Cr2AlN, which is significantly higher than any Tc value known or predicted for any material in the M2AX family to date.

This focus article has been prepared by Marco Falchieri, Scott M. Reid, Craig S. Ross, Joe James, Alexander M. P. Byrne, Madalina Zamfir, Ian H. Brown and Ashley C. Banyard of the APHA; Glen Tyler and Emma Philip of NatureScot; and Will Miles of Scottish Oceans Institute, School of Biology, University of St Andrews.

Angiotensin converting enzyme 2 (ACE2) is a host cell membrane protein (receptor) that mediates the binding of coronavirus, most notably SARS coronaviruses in the respiratory and gastrointestinal tracts. Although SARS-CoV-2 infection is mainly confined to humans, there have been numerous incidents of spillback (reverse zoonoses) to domestic and captive animals. An absence of information on the spatial distribution of ACE2 in animal tissues limits our understanding of host species susceptibility. Here, we describe the distribution of ACE2 using immunohistochemistry (IHC) on histological sections derived from carnivores, ungulates, primates and chiroptera. Comparison of mink (Neovison vison) and ferret (Mustela putorius furo) respiratory tracts showed substantial differences, demonstrating that ACE2 is present in the lower respiratory tract of mink but not ferrets. The presence of ACE2 in the respiratory tract in some species was much more restricted as indicated by limited immunolabelling in the nasal turbinate, trachea and lungs of cats (Felis catus) and only the nasal turbinate in the golden Syrian hamster (Mesocricetus auratus). In the lungs of other species, ACE2 could be detected on the bronchiolar epithelium of the sheep (Ovis aries), cattle (Bos taurus), European badger (Meles meles), cheetah (Acinonyx jubatus), tiger and lion (Panthera spp.). In addition, ACE2 was present in the nasal mucosa epithelium of the serotine bat (Eptesicus serotinus) but not in pig (Sus scrofa domestica), cattle or sheep. In the intestine, ACE2 immunolabelling was seen on the microvillus of enterocytes (surface of intestine) across various taxa. These results provide anatomical evidence of ACE2expression in a number of species which will enable further understanding of host susceptibility and tissue tropism of ACE2 receptor-mediated viral infection

Buchwald–Hartwig amination is one of the most important methods for the synthesis of N-arylamines and is widely employed for the synthesis of potential pharmaceuticals, natural products, and other fine chemicals. The reaction usually uses a Pd(0) catalyst such as Pd(dba)2 and (±)-BINAP in the presence of a base, and toluene is the most commonly used solvent. However, there are significant safety, toxicological, and environmental hazards associated with the use of toluene. Herein, we demonstrate the successful application of 2,2,5,5-tetramethyloxolane (TMO), a solvent with a similar property profile to toluene, for Buchwald–Hartwig amination reactions for coupling a wide range of primary and secondary amines with aryl bromides. When NaOt-Bu was used as the base, similar yields were obtained in toluene and TMO. In contrast, using Cs2CO3, TMO outperformed toluene significantly for electron-deficient aryl bromides that could be susceptible to nucleophilic attack. To showcase the use of TMO as a solvent for Buchwald–Hartwig aminations, the synthesis of a key intermediate in the route to smoothened (SMO) receptor antagonist drug candidate SEN826 was successfully accomplished in TMO. Improved metrics and reduction in residual palladium in the isolated amines demonstrate further benefits in the substitution of toluene with TMO in Buchwald–Hartwig aminations.

On May 4-5, 2022, a meeting of multidisciplinary stakeholders in the prevention and treatment of venous thromboembolism (VTE) after trauma was convened by the Coalition for National Trauma Research (CNTR), funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH/NHLBI), and hosted by the American College of Surgeons (ACS) in Chicago, Illinois. This consensus conference gathered more than 40 in-person and 80 virtual attendees, including trauma surgeons, other physicians, thrombosis experts, nurses, pharmacists, researchers, and patient advocates. The objectives of the meeting were two-fold: 1) to review and summarize the present state of the scientific evidence regarding VTE prevention strategies in injured patients, and 2) to develop consensus on future priorities in VTE prevention implementation and research gaps.To achieve these objectives, the first part of the conference consisted of talks from physician leaders, researchers, clinical champions, and patient advocates to summarize the current state of knowledge of VTE pathogenesis and prevention in patients with major injury. Video recordings of all talks and accompanying slides are freely available on the conference website. (https://www.nattrauma.org/research/research-policies-templates-guidelines/vte-conference/) Following this curriculum, the second part of the conference consisted of a series of small-group breakout sessions on topics potentially requiring future study. Through this process, research priorities were identified and plans of action to develop and undertake future studies were defined.The 2022 Consensus Conference to Implement Optimal VTE Prophylaxis in Trauma answered the National Trauma Research Action Plan call to define a course for future research into preventing thromboembolism after trauma. A multidisciplinary group of clinical champions, physicians, scientists, and patients delineated clear objectives for future investigation to address important, persistent key knowledge gaps. The series of papers from the conference outline the consensus based on the current literature and a roadmap for research to answer these unanswered questions.

Pseudokinases, so named because they lack one or more conserved canonical amino acids that define their catalytically-active relatives, have evolved a variety of biological functions in both prokaryotic and eukaryotic organisms. Human PSKH2 is closely related to the canonical kinase PSKH1, which maps to the CAMK family of protein kinases. Primates encode PSKH2 in the form of a pseudokinase, which is predicted to be catalytically inactive due to loss of the invariant catalytic Asp residue. Although the biological role(s) of vertebrate PSKH2’s remains unclear, we previously identified species-level adaptions in PSKH2 that have led to the appearance of kinase or pseudokinase variants in vertebrate genomes alongside a canonical PSKH1 paralog. In this paper we confirm that, as predicted, PSKH2 lacks detectable protein phosphotransferase activity, and exploit structural informatics, biochemistry and cellular proteomics to begin to characterise vertebrate PSKH2 orthologues. AlphaFold 2-based structural analysis predicts functional roles for both the PSKH2 N- and C-regions that flank the pseudokinase domain core, and cellular truncation analysis confirms that the N-terminal domain, which contains a conserved myristoylation site, is required for both stable human PSKH2 expression and localisation to a membrane-rich subcellular fraction containing mitochondrial proteins. Using mass spectrometry-based proteomics, we confirm that human PSKH2 is part of a cellular mitochondrial protein network, and that its expression is regulated through client-status within the HSP90/Cdc37 molecular chaperone system. HSP90 interactions are mediated through binding to the PSKH2 C-terminal tail, leading us to predict that this region might act as both a cis and trans regulatory element, driving outputs linked to the PSKH2 pseudokinase domain that are important for functional signalling.

Introduction Trauma patients have diverse resource needs due to variable mechanisms and injury patterns. The aim of this study was to build a tool that uses only data available at time of admission to predict prolonged hospital length of stay (LOS). Methods Data was collected from the trauma registry at an urban level one adult trauma center and included patients from 1/1/2014 to 3/31/2019. Trauma patients with one or fewer days LOS were excluded. Single layer and deep artificial neural networks were trained to identify patients in the top quartile of LOS and optimized on area under the receiver operator characteristic curve (AUROC). The predictive performance of the model was assessed on a separate test set using binary classification measures of accuracy, precision, and error. Results 2953 admitted trauma patients with more than one-day LOS were included in this study. They were 70% male, 60% white, and averaged 47 years-old (SD: 21). 28% were penetrating trauma. Median length of stay was 5 days (IQR 3-9). For prediction of prolonged LOS, the deep neural network achieved an AUROC of 0.80 (95% CI: 0.786-0.814) specificity was 0.95, sensitivity was 0.32, with an overall accuracy of 0.79. Conclusion Machine learning can predict, with excellent specificity, trauma patients who will have prolonged length of stay with only physiologic and demographic data available at the time of admission. These patients may benefit from additional resources with respect to disposition planning at the time of admission.

Blastobotrys aristata is a member of the Trichomonascaceae family in the order Saccharomycetales. Here, we present the genome sequence of B. aristata UCD613, which was isolated from soil in Dublin, Ireland. This genome is 13.3 Mb and was assembled into 4 chromosome-size scaffolds of >2.2 Mb in size plus a mitochondrial genome scaffold.

SummaryPeroxiredoxins (Prdx) utilize reversibly oxidized cysteine residues to reduce peroxides but also to promote H2O2signal transduction, including H2O2-induced activation of P38 MAPK. Prdx form H2O2-induced disulfide complexes with many proteins, including multiple kinases involved in P38 MAPK signaling. Here we show that a genetically-encoded fusion between Prdx and the P38 MAPK is sufficient to hyperactivate the kinase in yeast and human cells by a mechanism that does not require the H2O2-sensing cysteine of the Prdx. In yeast, we demonstrate that a P38-Prdx fusion protein compensates for the loss of a scaffold protein and upstream MAP3K kinase activity, driving entry into mitosis. Based on our findings, we propose that the H2O2-induced formation of Prdx-MAPK disulfide complexes provides a scaffold and signaling platform for MAPKK-MAPK signaling. The demonstration that formation of a complex with a Prdx can be sufficient to modify the activity of a kinase has broad implications for peroxide-based signal transduction in eukaryotes.HighlightsP38-Prdx complexes increase P38 (Sty1/MAPK14) phosphorylation in yeast and human cellsTheS. pombePrdx promotes transient thioredoxin-mediated oxidation of a MAPK tyrosine phosphataseP38-Prdx complexes increase P38(Sty1) activity by phosphatase and MAP3K-independent mechanismsP38-Prdx complexes increase the stability and phosphorylation of theS. pombeP38 MAPKK (Wis1)Non-canonical, H2O2-induced autophosphorylation contributes to activation of the Wis1 MAPKK

Extreme temperatures have warmed substantially over recent decades and are projected to continue warming in response to future climate change. Warming of extreme temperatures is amplified over land, with severe implications for human health, wildfire risk and food production. Using simulations from 18 climate models, I show that hot days over tropical land warm substantially more than the average day. For example, warming of the hottest 5% of land days is a factor of 1.21 ± 0.07 larger than the time-mean warming averaged across models. The climate change response of extreme temperatures over tropical land is interpreted using a theory based on atmospheric dynamics. According to the theory, warming is amplified for hot land days because those days are dry, which is termed the ‘drier get hotter’ mechanism. Changes in near-surface relative humidity further increase tropical land warming, with decreases in land relative humidity being particularly important. The theory advances physical understanding of the tropical climate and highlights land surface dryness as a key factor determining how extreme temperatures respond to climate change. Climate change warms extreme hot days over tropical land more strongly than the mean temperature as hot days are dry, according to a new theory and analysis of global climate models.

Background Social anxiety disorder (SAD) is a chronic and disabling psychiatric disorder associated with low levels of help-seeking. To date, however, scarce research has examined the epidemiology of SAD in veterans. This study examined the prevalence, comorbidities and incremental burden of SAD in relation to suicidality and functioning in a representative sample of U.S. military veterans. Methods A nationally representative sample of 3,157 U.S. veterans completed a web survey containing measures of SAD symptoms, trauma history, psychiatric history and functioning. Multivariable analyses were conducted to examine associations between SAD and psychiatric comorbidities, suicidality and functioning. Results A total 9.5% (n = 272) of the sample screened positive for lifetime SAD. Veterans with SAD were more likely than those without SAD to be younger, female, single, racial/ethnic minorities and to have experienced childhood abuse. They also had substantially elevated rates of comorbid psychiatric disorders, particularly lifetime major depression (odds ratio [OR]=5.8) and posttraumatic stress disorder (OR=3.1), as well as current suicidal ideation (OR=3.3). Veterans with SAD scored lower on measures of functioning, particularly social, emotional and mental health functioning (d’s=0.21–0.34). Limitations Data were collected cross-sectionally using self-report. Conclusions SAD in U.S. veterans is prevalent and associated with psychiatric comorbidities, functional impairment and a more than 3-fold greater risk for suicidal ideation . Given that SAD is associated with low treatment seeking and engagement, it may be undetected and undertreated relative to other psychiatric morbidities. These results underscore the importance of screening, monitoring and treating SAD in this population along with other prevalent mental disorders.

Background Left-sided cardiac volume overload (LCVO) can cause fluid accumulation in lung tissue changing the distribution of ventilation, which can be evaluated by electrical impedance tomography (EIT). Objectives To describe and compare EIT variables in horses with naturally occurring compensated and decompensated LCVO and compare them to a healthy cohort. Animals Fourteen adult horses, including university teaching horses and clinical cases (healthy: 8; LCVO: 4 compensated, 2 decompensated). Methods In this prospective cohort study, EIT was used in standing, unsedated horses and analyzed for conventional variables, ventilated right (VAR) and left (VAL) lung area, linear-plane distribution variables (avg-max VΔZLine, VΔZLine), global peak flows, inhomogeneity factor, and estimated tidal volume. Horses with decompensated LCVO were assessed before and after administration of furosemide. Variables for healthy and LCVO-affected horses were compared using a Mann-Whitney test or unpaired t-test and observations from compensated and decompensated horses are reported. Results Compared to the healthy horses, the LCVO cohort had significantly less VAL (mean difference 3.02; 95% confidence interval .77-5.2; P = .02), more VAR (−1.13; −2.18 to −.08; P = .04), smaller avg-max VΔZLLine (2.54; 1.07-4.00; P = .003) and VΔZLLine (median difference 5.40; 1.71-9.09; P = .01). Observation of EIT alterations were reflected by clinical signs in horses with decompensated LCVO and after administration of furosemide. Conclusions and Clinical Importance EIT measurements of ventilation distribution showed less ventilation in the left lung of horses with LCVO and might be useful as an objective assessment of the ventilation effects of cardiogenic pulmonary disease in horses.

In Philadelphia, PA, police and emergency medical services (EMS) transport patients with firearm injuries. Prior studies evaluating this system have lacked reliable prehospital times. By linking police and hospital data sets, we established a complete timeline from firearm injury to outcome. We hypothesized that police-transported patients have shorter prehospital times that, in turn, are associated with improved survival and increased unexpected survivorship at 6 and 24 hours.This retrospective study linked patient-level data from OpenDataPhilly Shooting Victims and the Pennsylvania Trauma Systems Foundation. All adults transported to a Level I or II trauma center after firearm injury in Philadelphia from 2015 to 2018 were included. Patient-level characteristics were compared between cohorts; unexpected survivors were identified using Trauma Score-Injury Severity Score. Multiple regression estimated risk-adjusted associations between transport method, prehospital time, and outcomes.Police-transported patients (n = 977) had significantly shorter prehospital times than EMS-transported patients (n = 320) (median, 9 minutes [interquartile range, 7-12 minutes] vs. 21 minutes [interquartile range, 16-29 minutes], respectively; p0.001). Police-transported patients were more often severely injured than those transported by EMS (60% vs. 50%, p = 0.002). After adjusting for confounders, police-transported patients had improved survival relative to EMS on hospital arrival (87% vs. 84%, respectively, p = 0.035), but not at 6 hours (79% vs. 78%, respectively, p = 0.126) or 24 hours after arrival (76% vs. 76%, respectively, p = 0.224). Compared with EMS, police-transported patients were significantly more likely to be unexpected survivors at 6 hours (6% vs. 2%, respectively, p0.001) and 24 hours (3% vs. 1%, respectively, p = 0.021).Police-transported patients had more severe injuries, shorter prehospital times, and increased likelihood of unexpected survival compared with EMS-transported patients. After controlling for confounders, patient physiology and injury severity represent meaningful determinants of mortality in our mature trauma system, indicating an ongoing opportunity to optimize in-hospital care. Future studies should investigate causes of death among unexpected early survivors to mitigate preventable mortality.Prognostic/Epidemiological, Level III.

Background Scotland first demonstrated that adherence to nationally agreed hip fracture standards improve patient survival, reduces the duration of admission, and reduces the need for high dependency care. Our study aims to assess adherence to the Irish Hip Fracture Standards (IHFS) in our hospital for 2021 amidst the COVID-19 pandemic, translating to improved clinical outcomes for our patients. Methods The IHF database was retrospectively analysed, comparing quarters 1-4 in 2021 with our 2020 results. Results IHFS1, patient time to the ward < 4hours, was maintained at 67% in 2021 versus 71% overall in 2020. There was improvement in IHFS2, time to surgery within 48 hours, up to 73% in 2021 versus 66% in 2020. IHFS3 was 4% in 2021 versus 3% overall in 2020. Further improvements were noted for IHFS4, with 95% of patients reviewed by a Geriatrician in 2021 versus 87% in 2020. IHFS5 also improved with 97% of patients receiving a bone health assessment in 2021 versus 87% in 2020. Moreover, IHFS6, improved with 97% of patients undergoing a specialised falls assessment in 2021 versus 87% in 2020. Conclusion The improvement in 2021 figures is reflective of the return of redeployed services during the COVID-19 pandemic inclusive of the Orthogeriatric Service, the Fracture Liaison Service Advanced Nurse Practitioner, the Trauma Co-ordinator, and the specialist Orthopaedic ward complete with its Orthopaedic nurses and Multi-Disciplinary Team, and improved Emergency Department pathways. These continued improvements in the IHFS further emphasise that success is dependent on a team that is joined at the hip

Background Nationally agreed hip fracture standards have contributed to the improvement of outcomes in hip fracture patients. In 2020, our hospital was awarded “The Golden Hip” for achieving highest compliance with Irish Hip Fracture Standards (IHFS) nationally for 2019. Methods Data from the Irish Hip Fracture Database (IHFD)was retrospectively analysed to assess our performance in 2020 versus 2019 in hip fracture patients over sixty. Multiple quality improvement interventions were put in place throughout 2019 to ensure improvement in IHFS1-6 compliance: Creation of the Hip Fracture Pathway Subgroup, IHFS 1 Breaches Audit, Orthogeriatric input at Orthopaedic inductions, weekly Multi-disciplinary Team meetings, a Nutritional Hip Fracture Pathway and addition of the Fracture Liaison Service Advanced Nurse Practitioner. Results There were 239 hip fracture patients in 2020 vs 249 in 2019. IHFS1 compliance improved with the percentage of patients admitted to the Orthopaedic ward within 4 hours increasing to 71% in 2020 from 56% in 2019. There was improvement in IHFS2-time to surgery Conclusion Lower results for IHFS 4,5 and 6 reflect the arrival of the COVID-19 pandemic which led to redeployment of the Orthogeriatric Service and redeployment of the MDT from end of Q1 to Q3. When services in 2020 were preserved,1 in 2 hip fracture patients met all IHFS, vs 1 in 3 patients in 2019. Despite the pandemic, we continued to achieve the highest level of IHFS compliance nationally, being awarded a second consecutive “Golden Hip” for 2020.

The opportunistic pathogen Pseudomonas aeruginosa is one of leading causes of disability and mortality worldwide and the world health organisation has listed it with the highest priority for the need of new antimicrobial therapies. P. aeruginosa strains responsible for the poorest clinical outcomes express either ExoS or ExoU, which are injected into target host cells via the type III secretion system (T3SS). ExoS is a bifunctional cytotoxin that promotes intracellular survival of invasive P. aeruginosa by preventing targeting of the bacteria to acidified intracellular compartments. ExoU is a phospholipase which causes destruction of host cell plasma membranes, leading to acute tissue damage and bacterial dissemination. Fluoroquinolones are usually employed as a first line of therapy as they have been shown to be more active against P. aeruginosa in vitrothan other antimicrobial classes. Their overuse over the past decade, however, has resulted in the emergence of antibiotic resistance. In certain clinical situations, aminoglycosides have been shown to be more effective then fluoroquinolones, despite their reduced potency towards P. aeruginosa in vitro. In this study, we evaluated the effects of fluoroquinolones (moxifloxacin and ciprofloxacin) and aminoglycosides (tobramycin and gentamycin) on T3SS expression and toxicity, in corneal epithelial cell infection models. We discovered that tobramycin disrupted T3SS expression and reduced both ExoS and ExoU mediated cytotoxicity, protecting infected HCE-t cells at concentrations below the minimal inhibitory concentration (MIC). The fluoroquinolones moxifloxacin and ciprofloxacin, however, up-regulated the T3SS and did not inhibit and may have increased the cytotoxic effects of ExoS and ExoU.

Torulaspora quercuum is an ascomycete yeast first isolated in 2009. Here, we present the genome sequence of T. quercuum isolate UCD657, which was isolated from soil in Ireland. This genome is 10.4 Mb and was assembled into 8 chromosome-sized scaffolds of >1 Mb in size, plus a mitochondrial genome scaffold.

Background This study was part of a 5-year, HRB-funded research project about hospital doctor retention and emigration. Methods In 2021, we conducted a Mobile Instant Messaging Ethnography (MIME) with 28 hospital doctors in Ireland. This involved interviewing doctors via Zoom and engaging them in a 12-week work-related conversation via WhatsApp. Results Our findings illustrate that the pandemic intensified already difficult working conditions. Respondents described working in an under-staffed and under-resourced system, in which they were unable to protect their own wellbeing or achieve a work-life balance. Morale was low and few had hope of health system improvement. Conclusions The findings reveal a workforce under strain and raise concerns about health worker wellbeing and health worker attrition, post-pandemic. However, they also highlight the importance (and value) of listening to the voices of frontline health workers and using their insights to inform and enhance retention policies.

Saccharomyces genomes are highly collinear and show relatively little structural variation, both within and between species of this yeast genus. We investigated the only common inversion polymorphism known in S. cerevisiae, which affects a 24-kb ‘flip/flop’ region containing 15 genes near the centromere of chromosome XIV. The region exists in two orientations, called reference (REF) and inverted (INV). Meiotic recombination in this region is suppressed in crosses between REF and INV orientation strains such as the BY x RM cross. We find that the inversion polymorphism is at least 17 million years old because it is conserved across the genus Saccharomyces. However, the REF and INV isomers are not ancient alleles but are continually being re-created by re-inversion of the region within each species. Inversion occurs due to continual homogenization of two almost identical 4-kb sequences that form an inverted repeat (IR) at the ends of the flip/flop region. The IR consists of two pairs of genes that are specifically and strongly expressed during the late stages of sporulation. We show that one of these gene pairs, YNL018C/YNL034W, codes for a protein that is essential for spore formation. YNL018C and YNL034W are the founder members of a gene family, Centroid, whose members in other Saccharomycetaceae species evolve fast, duplicate frequently, and are preferentially located close to centromeres. We tested the hypothesis that Centroid genes are a meiotic drive system, but found no support for this idea.

A necessary ingredient for extending the BFKL equation to next-to-next-to-leading logarithmic (NNLL) accuracy is the one-loop central emission vertex (CEV) for two gluons which are not strongly ordered in rapidity. Here we consider the one-loop six-gluon amplitude in $\mathcal{N}=4$ super Yang-Mills (SYM) theory in a central next-to-multi-Regge kinematic (NMRK) limit, we show that its dispersive part factorises in terms of the two-gluon CEV, and we use it to extract the one-loop two-gluon CEV for any helicity configuration within this theory. This is a component of the two-gluon CEV in QCD. Although computed in the NMRK limit, both the colour structure and the kinematic dependence of the two-gluon CEV capture much of the complexity of the six-gluon amplitudes in general kinematics. In fact, the transcendental functions of the latter can be conveniently written in terms of impact factors, trajectories, single-emission CEVs and a remainder, which is a function of the conformally invariant cross ratios which characterise the six-gluon amplitudes in planar $\mathcal{N}=4$ SYM. Finally, as expected, in the MRK limit the two-gluon CEV neatly factorises in terms of two single-emission CEVs., Comment: 85 pages, 13 figures

A high-throughput computational method is used to predict 39 new superconductors in the Ti-based M$$_2$$ 2 AX phases, and the best candidates are then studied in more detail using density functional theory electron–phonon coupling calculations. The detailed calculations agree with the simple predictions, and Ti$$_2$$ 2 AlX (X: B, C and N) materials are predicted to have higher values of $$T_c$$ T c than any currently known hexagonal M$$_2$$ 2 AX phases. The electronic states at the Fermi level are dominated by the Ti 3d states. The choice of X (X: B, C and N) has a significant impact on the electronic density of states but not on the phonon characteristics. The electron–phonon coupling parameter for Ti$$_2$$ 2 AlX (X: B, C and N) was determined to be 0.685, 0.743 and 0.775 with a predicted $$T_c$$ T c of 7.8 K, 10.8 K and 13.0 K, respectively.

Journal of high energy physics 04(4), 105 (2021). doi:10.1007/JHEP04(2021)105, Large logarithmic corrections in $ \hat{s}/{p}_t^2 $ lead to substantial variations in the perturbative predictions for inclusive W-plus-dijet processes at the Large Hadron Collider. This instability can be cured by summing the leading-logarithmic contributions in $ \hat{s}/{p}_t^2 $ to all orders in ��$_{s}$. As expected though, leading logarithmic accuracy is insufficient to guarantee a suitable description in regions of phase space away from the high energy limit.We present (i) the first calculation of all partonic channels contributing at next-to-leading logarithmic order in W-boson production in association with at least two jets, and (ii) bin-by-bin matching to next-to-leading fixed-order accuracy. This new perturbative input is implemented in High Energy Jets, and systematically improves the description of available experimental data in regions of phase space which are formally subleading with respect to $ \hat{s}/{p}_t^2 $., Published by SISSA, [Trieste]

Sulfated carbohydrate metabolism is a fundamental process, which occurs in all domains of life. Carbohydrate sulfatases are enzymes that remove sulfate groups from carbohydrates and are essential to the depolymerisation of complex polysaccharides. Despite their biological importance, carbohydrate sulfatases are poorly studied and challenges remain in accurately assessing the activity, specificity and kinetic parameters. Most notably, separation of desulfated products from sulfated substrates is currently a time-consuming process. In this paper, we describe the development of rapid capillary electrophoresis coupled to substrate fluorescence detection as a high-throughput and facile means of analysing carbohydrate sulfatase activity. The approach has utility for the determination of both kinetic and inhibition parameters and is based on existing microfluidic technology coupled to a new synthetic fluorescent 6S-GlcNAc carbohydrate substrate. Furthermore, we compare this technique in terms of both time and resources, to high performance anion exchange chromatography and NMR-based methods, which are the two current ‘gold standards’ for enzymatic carbohydrate sulfation analysis. Our study clearly demonstrates the advantages of mobility shift assays for the quantification of near real-time carbohydrate desulfation by purified sulfatases, and could support the search for small molecule inhibitors of these disease-associated enzymes.One sentence summarySulfatases remove sulfate groups from biomolecules; in this study we report a rapid and robust capillary electrophoresis assay for the quantification of carbohydrate desulfation.

This study aims to identify modifiable factors related to firearm homicide (FH).Many socioeconomic, legislative and behavioral risk factors impact FH. Most studies have evaluated these risk factors in isolation, but they coexist in a complex and ever-changing American society. We hypothesized that both restrictive firearm laws and socioeconomic support would correlate with reduced FH rates.To perform our ecologic cross-sectional study, we queried the Centers for Disease Control (CDC) Wide-ranging ONline Data for Epidemiologic Research (WONDER) and Federal Bureau of Investigation (FBI) Uniform Crime Reporting (UCR) for 2013-2016 state FH data. We retrieved firearm access estimates from the RAND State-Level Firearm Ownership Database. Alcohol use and access to care data were captured from the CDC Behavioral Risk Factor Surveillance System (BRFSS). Detached youth rates, socioeconomic support data and poverty metrics were captured from US Census data for each state in each year. Firearm laws were obtained from the State Firearms Law Database. Variables with significant FH association were entered into a final multivariable panel linear regression with fixed effect for state.A total of 49,610 FH occurred in 2013-2016 (median FH rate: 3.9:100,000, range: 0.07-11.2). In univariate analysis, increases in concealed carry limiting laws (P=0.012), detached youth rates (P0.001), socioeconomic support (P0.001) and poverty rates (P0.001) correlated with decreased FH. Higher rates of heavy drinking (P=0.036) and the presence of stand your ground doctrines (P=0.045) were associated with increased FH. Background checks, handgun limiting laws, and weapon access were not correlated with FH. In multivariable regression, increased access to food benefits for those in poverty [β: -0.132, 95% confidence interval (CI): -0.182 to -0.082, P0.001] and laws limiting concealed carry (β: -0.543, 95% CI: -0.942 to -0.144, P=0.008) were associated with decreased FH rates. Allowance of stand your ground was associated with more FHs (β: 1.52, 95% CI: 0.069-2.960, P0.040).The causes and potential solutions to FH are complex and closely tied to public policy. Our data suggests that certain types of socioeconomic support and firearm restrictive legislation should be emphasized in efforts to reduce firearm deaths in America.

More than 20,000 firearm suicides occur every year in America. Firearm restrictive legislation, firearm access, demographics, behavior, access to care, and socioeconomic metrics have been correlated to firearm suicide rates. Research to date has largely evaluated these contributors singularly. We aimed to evaluate them together as they exist in society. We hypothesized that state firearm laws would be associated with reduced firearm suicide rates.We acquired the 2013 to 2016 data for firearm suicide rates from The Centers for Disease Control Wide-ranging Online Data for Epidemiologic Research. Firearm laws were obtained from the State Firearms Law Database. Depression rates and access to care were obtained from the Behavioral Risk Factor Surveillance System and Occupational Employment and Wage Statistics program. Population demographics, poverty, and access to social support were obtained from the American Community Survey. Firearm access estimates were retrieved from the National Instant Criminal Background Check System. We used a univariate panel linear regression with fixed effect for state and firearm suicide rates as the outcome. We created a final multivariable model to determine the adjusted associations of these factors with firearm suicide rates.In univariate analysis, firearm access, heavy drinking behavior, demographics, and access to care correlated to increased firearm suicide rates. The state proportion identifying as white and the proportion of those in poverty receiving food benefits correlated to decreased firearm suicide rates. In multivariable regression, only heavy drinking (β, 0.290; 95% confidence interval, 0.092-0.481; P = .004) correlated to firearm suicides rates increases.During our study, few firearm laws changed. Heavy drinking behavior association with firearm suicide rates suggests an opportunity for interventions exists in the health care setting.

A high-throughput computational method is used to predict 39 new superconductors in the Ti-based M[Formula: see text]AX phases, and the best candidates are then studied in more detail using density functional theory electron-phonon coupling calculations. The detailed calculations agree with the simple predictions, and Ti[Formula: see text]AlX (X: B, C and N) materials are predicted to have higher values of [Formula: see text] than any currently known hexagonal M[Formula: see text]AX phases. The electronic states at the Fermi level are dominated by the Ti 3d states. The choice of X (X: B, C and N) has a significant impact on the electronic density of states but not on the phonon characteristics. The electron-phonon coupling parameter for Ti[Formula: see text]AlX (X: B, C and N) was determined to be 0.685, 0.743 and 0.775 with a predicted [Formula: see text] of 7.8 K, 10.8 K and 13.0 K, respectively.

Uncertainty exists re risk:benefit of proximal intestinal exclusion with EB, a novel endoscopic duodenal jejunal liner device for obesity, both with and without diabetes. In view of this, during 2017, an independent, secure, on line registry was established under the auspices of the Association of British Clinical Diabetologists, for the collection of safety and efficacy data worldwide. As of December 2021, data had been entered on 10patients {age 52.1 ± 10.3 year, 53% male, 87% diabetes, BMI 41.1 ± 8.9 kg/m2} and showed many benefits (Table 1) . There were 43 (4.2%) SAEs and 139 (13.9%) less serious AEs (Table 2) . All SAE patients made a full recovery and most derived significant benefit. The benefits of EB therapy are likely to reduce the complications of diabetes. This international data from the EB registry suggests that the likely benefits of EB, far outweigh the risks Disclosure R.E.J. Ryder: None. J.P. Teare: None. A. Ruban: None. M. Haluzik: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Abbott Diabetes, AstraZeneca, Lilly Diabetes, Novartis AG. L. Munro: None. H. Frydenberg: None. J.J. McMaster: None. S. Fishman: None. R.V. Cohen: Advisory Panel; GI Dynamics. Research Support; Johnson & Johnson, Medtronic. C.M. Aboud: None. G.J. Holtmann: Research Support; AbbVie Inc., Allergan, Arena Pharmaceuticals, Inc., Bayer, Bristol Myers, Datapharm Australia Pty Ltd Commonwealth Laboratories, Pty Limited, Eli Lilly Australia Pty Limited, F.Hoffmann-La Roche Limited, Falk Foundation, Falk GmbH and Co Kg, GI Therapies Pty Ltd, Gilead Sciences Pty Limited, MedImmune Ltd Celgene Pty Limited, Mylan, Nestle Pty Ltd, Prometheus Laboratories, Quintiles Pty Limited, Servatus, Takeda Development Center Asia, Pty Ltd, Vital Food Processors Ltd. C. de Jonge: None. J. Greve: Advisory Panel; GI Dynamics. Other Relationship; Bariatric Solutions International, Ethicon, Inc. J.C. Mason: None. H. Sourij: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk. Research Support; Boehringer Ingelheim International GmbH, Sanofi. Speaker's Bureau; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk. R. Drummond: Research Support; Fractyl Health, Inc. Speaker's Bureau; AstraZeneca, Bristol-Myers Squibb Company. B. McGowan: Advisory Panel; Johnson & Johnson, Lilly, Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; AstraZeneca, Novo Nordisk. Stock/Shareholder; Reset Health. S.A. Amiel: Advisory Panel; Medtronic, Novo Nordisk. Other Relationship; Sanofi. M. Yadagiri: None. P. Sen Gupta: None. K. Laubner: None. J. Seufert: Advisory Panel; Abbott, Sanofi-Aventis Deutschland GmbH. Research Support; Boehringer Ingelheim International GmbH. Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. Funding Association of British Clinical Diabetologists

Human Tribbles 2 (TRIB2) is a cancer-associated pseudokinase with a broad human protein interactome, including the well-studied AKT, C/EBPα and MAPK modules. Several lines of evidence indicate that human TRIB2 promotes cell survival and drug-resistance in solid tumors and blood cancers and is therefore of interest as a potential therapeutic target, although its physiological functions remain relatively poorly understood. The unique TRIB2 pseudokinase domain lacks the canonical 'DFG' motif, and subsequently possesses very low affinity for ATP in both the presence and absence of metal ions. However, TRIB2 also contains a unique cysteine-rich αC-helix, which interacts with a conserved peptide motif in its own carboxyl-terminal tail. This regulatory flanking region drives regulated interactions with distinct E3 ubiquitin ligases that serve to control the stability and turnover of TRIB2 client proteins. TRIB2 is also a low-affinity target of several known small-molecule protein kinase inhibitors, which were originally identified using purified recombinant TRIB2 proteins and a thermal shift assay. In this chapter, we discuss laboratory-based procedures for purification, stabilization and analysis of human TRIB2, including screening procedures that can be used for the identification of both reversible and covalent small molecule ligands.

Social Innovation and Deep Institutional Innovation for Sustainability and Human Development

Methylation of acetoin with dimethyl carbonate was performed in a sustainable one-step process, with improved process mass intensity (PMI) and atom economy compared to previously published methods. The resulting product, 3-methoxybutan-2-one (MO) was successfully evaluated as a bio-based solvent, while both Kamlet–Taft solvatochromic parameters and Hansen solubility parameters demonstrate its potential viability in the substitution of chlorinated solvents. MO exhibited a low peroxide forming potential and a negative Ames mutagenicity test and was successfully used as a solvent in a Friedel–Crafts acylation (79% yield compared to 77% in dichloromethane) and for N-alkylations. MO is a renewable oxygenated solvent, with the potential ability to substitute carcinogenic halogenated solvents in some applications.