Background and Purpose: Improvement of cognitive deficits in schizophrenia remains an unmet need due to the lack of new therapies and drugs. Recent studies have reported that fingolimod, an immunomodulatory drug for treating multiple sclerosis, demonstrates anti-inflammatory and neuroprotective effects in several neurological disease models. This suggests its usefulness for ameliorating cognitive dysfunction in schizophrenia. Herein, we assessed the efficacy profile and mechanism of fingolimod in a rat model of phencyclidine (PCP)-induced schizophrenia. Experimental Approach: Sprague-Dawley rats were treated with PCP for 14 days. The therapeutic effect of fingolimod on cognitive function was assessed using the Morris water maze and fear conditioning tests. Hippocampal neurogenesis and the expression of astrocytes and microglia were evaluated by immunostaining. Cytokine expression was quantified using multiplexed flow cytometry. Brain-derived neurotrophic factor expression and phosphorylation of extracellular signal-regulated kinase were determined using western blot analysis. Key Results: Fingolimod attenuated cognitive deficits and restored hippocampal neurogenesis in a dose-dependent manner in PCP-treated rats. Fingolimod treatment exerted anti-inflammatory effects by inhibiting microglial activation and IL-6 and IL-1β pro-inflammatory cytokine expression. The underlying mechanism involves the upregulation of brain-derived neurotrophic factor protein expression and activation of the extracellular signal-regulated kinase signalling pathway. Conclusion and Implications: To the best of our knowledge, this is the first preclinical study to assess the effects of fingolimod on cognitive function in schizophrenia models. Our results support the role of the immune system in cognitive alterations in schizophrenia and highlight the potential of immunomodulatory strategies to improve cognitive deficits in schizophrenia.

Introduction Extracorporeal membrane oxygenation (ECMO) is implemented as a rescue therapy in COVID-19 related acute distress respiratory syndrome (ARDS) and refractory hypoxemia. Google trends (GT) is an ongoing-developing web-kit providing feedback on specific population’s interests. This study uses GT to analyze the United States (US) general population interest in ECMO as COVD-19/ARDS salvage therapy. Methods GT was used to access data searched for the term ECMO and COVID-19. The gathered information included data from March 2020 through July 2021 within US territories. Search frequency, time intervals, sub-regions, frequent topics of interest, and related searches were analyzed. Data was reported as search frequency on means, and a value of 100 represented overall peak popularity. Results The number of Google searches related to the terms ECMO and COVID-19 has surged and sustained interest over time ever since the initial reports of COVID-19 in the US, from an initial mean of 34% in March 2020 to a 100% interest by April 2020, resulting in an up-to-date overall average of 40% interest. Over time West Virginia, Gainesville, and Houston, lead the frequency of searches in sub-region, metro and city areas, respectively. Top search terms by frequency include: ECMO machine, COVID ECMO, what is ECMO, ECMO treatment and VV ECMO. Parallel to this, the related rising terms are: COVID ECMO, ECMO machine COVID, ECMO for COVID, ECMO machine coronavirus, and ECMO vs ventilator. Seemingly, medical-relevant websites fail to adequately address these for patient therapeutic education (PTE) purposes. Conclusions GT complements the understanding of interest in ECMO for COVID-19. When properly interpreted, the use of these trends can potentially improve on PTE and therapy awareness via specific medical relevant websites.

Often described as the world's most deadly infectious disease, Tuberculosis remains a serious health threat in many parts of the world, especially in the developing countries. One of the social barriers hindering TB patients to seek and complete medical attention is stigmatization. In this study, we incorporated stigmatization on a model published by Feng et al. last 2000. We obtained the basic reproduction number and showed conditions where multiple endemic equilibrium will exist depending on a reinfection threshold. The model predicted a significant increase in the basic reproduction number as the level of stigmatization increases. We used optimal control theory to investigate the effect of controls to combat stigmatization and compare these controls with the usual controls such as improving treatment and minimizing reinfection. Simulations show that although stigmatization controls are helpful, they are not enough to successfully control the disease. A combination of all the controls will be ideal and some optimal rates of doing it over time are given, depending on the perceived cost of implementation.

Numerical hydrodynamic models enable the simulation of hydraulic conditions under various scenarios and are thus suitable tools for hydropeaking related assessments. However, the choice of the necessary model complexity and the consequences of modelling choices are not trivial and only few guidelines exist. In this study we systematically evaluate numerical one-dimensional (1D) and two-dimensional (2D) hydrodynamic models with varying spatial resolution regarding their suitability as input for hydropeaking-sensitive, ecologically relevant hydraulic parameters (ERHPs), and their computational efficiency. The considered ERHPs include the vertical dewatering velocity, the wetted area variation between base and peak flow and the bed shear stress as a proxy for macroinvertebrate drift. We then also quantified the habitat suitability of brown trout for different life stages. The evaluation is conducted for three channel planforms with morphological characteristics representative for regulated Alpine rivers, ranging from alternating bars to a braiding river morphology. Our results suggest, that while a highly resolved 1D model is sufficient for accurate predictions of the dewatering velocity and wetted area in the less complex alternating bar morphology, a 2D model is recommended for more complex wandering or braiding morphologies. For the prediction of habitat suitability and bed shear stress, a 1D model appears to be always insufficient, and a highly resolved 2D model is suggested. Reducing the spatial resolution of 2D models leads to computational efficiency similar to 1D, while providing more accurate results. This study can serve as guideline for researchers and practitioners in the selection and setup of hydrodynamic models for hydropeaking.

Disseminated neoplasia (DN) is one of the most challenging and unrecognised diseases occurring in aquatic fauna. It has been diagnosed in four bivalve species from the Gulf of Gdańsk (Southern Baltic Sea) with the highest frequency in Limecola balthica (formerly Macoma balthica), reaching up to 94% in some populations. The aetiology of DN in the Baltic Sea has not yet been identified, with earlier studies trying to link its occurrence with environmental pollution. Taking into account recent research providing evidence that DN is horizontally transmitted as clonal cells between individuals in some bivalve species, we aimed to test whether DN is a transmissible cancer in the population of L. balthica from the Gulf of Gdańsk highly affected with cancer. We examined mitochondrial cytochrome c oxidase I (mtCOI) and elongation factor 1α (EF1α) sequences of genomes obtained from haemolymph and tissues of neoplastic and healthy individuals. Sequence analysis resulted in detection of an independent transmissible cancer lineage occurring in 4 neoplastic clams that is not present in healthy animals. This paper describes the first case of transmissible DN in the clam L. balthica providing further insights for studies on this disease.

1. Evergreen dwarf shrubs respond swiftly to warming in the cool and dry High Arctic, but their response in the warmer Low Arctic, where they are expected to be outcompeted by taller species under future warming, remains to be clarified. 2. Here, 12,528 annual growth increments, covering 122 years (1893-2014), were measured of 764 branches from 25 individuals of the evergreen dwarf shrub Cassiope tetragona from a Low-Arctic erect dwarf-shrub tundra site in western Greenland. In addition, branch initiation and mortality frequency time-series were developed. The influence of seasonal climate and correspondence with fluctuations in regional normalized difference vegetation index (NDVI), a satellite-proxy for vegetation productivity, were studied. 3. Winter temperatures were an important co-driver, summer temperatures the main driver of growth. During past and recent warm episodes, shrub growth diverged from summer temperatures. In recent decades, early summer precipitation has become the main growth-limiting factor for some individuals, likely through micro-topography-determined soil moisture availability, and more than half of the shrubs studied became irresponsive to summer temperatures. There was correspondence between climatic drivers, C. tetragona growth and branch initiation frequency, and satellite-observed vegetation productivity, suggesting the area’s shrub-dominated tundra vegetation is limited by similar climatic factors. Winter warming events were likely the predominant cause of branch mortality, while branching increased after years with poor growth and cooler-than-average summers. 4. Synthesis These findings show that the erect dwarf-shrub tundra in the Low Arctic has and will likely become less temperature- and increasingly moisture-limited and that winter warming supports shrub growth, but increased extreme winter warming event-frequency may increase branch mortality and vegetation damage. Such counter-acting mechanisms could offer an explanation for the vegetation stability observed over large parts of the Arctic.

Style transfer is one of the hottest topics around deep learning media these days. There are a number of reasons for this, including the demonstrability of the method leaning well into publication and the potential utility of making quick stylistic edits to photos. This combination of utility and ease of demonstration make style transfer one of the most popular first computer vision projects many data scientists, ML engineers, and AI enthusiasts undertake, such as imparting the style of Vincent van Gogh's "Starry Night" to a previously mundane landscape photograph. That being said, it is a rough science. Like many computer vision tasks, the challenge of transferring style on to the rougher and larger areas of an image is far easier than transferring that same style to the finer features of a face. Regions like the eyes and mouth in particular are very difficult to get an AI to approximate for generation correctly. In this tutorial 1 , we will look at JoJoGAN-a novel approach to conducting one-shot style transfer for facial images. This PyTorch-written architecture was constructed with the goal of capturing the stylistic details that have been historically difficult to account for, such as transferring style effects that conserve facial details like eye shape or mouth details. JoJoGAN aims to solve this problem by first approximating a paired training dataset and then finetuning a StyleGAN to perform one-shot face stylization. JoJoGAN is capable of intaking any single image of a face (ideally a high quality head shot of some kind), approximating the paired real data using GAN inversion, and using the data to minutely adjust a pre-trained StyleGAN2 model. The StyleGAN2 model is then made generalizable so that the imparted style can be subsequently applied to new images. Previous one and few shot attempts have approached their level of success, but JoJoGAN has managed to achieve an extremely high level of quality for the images it generates.

The worldwide diversity of contaminated sites, coupled with a scarcity of available land in urban spatial planning, has led to an increasing political significance for brownfield conservation and re-use to achieve land resource sustainability. In this study, economic or so-called rebound effects of land regeneration, are studied via a global meta-analysis on value fluctuation of surrounding property. To this end, a total of 91 observations from 28 HPM (Hedonic Pricing Model) studies were synthesized to conduct a meta-analysis following a conditional random-effects procedure. The empirical results indicate that, in line with expectations, the conservation and recycling of land resource indeed generate significant rebound in the implicit price of residential houses, especially for those located within 2 kilometers of contaminated sites. Before land remediation and re-use, dwellings closest in distance to contaminated sites experience the greatest value loss. On average, the depreciation in property values within the first 1km distance from a contaminated site is about 8.18%, significantly at the 1% level, while the corresponding adverse impact from 1 to 2 km distance is a 4.8% price premium significantly at the 5% level. The significance of the stigma or rebound effects depend on 12 attributes, in which, house age, location, FAR (Floor Area Ratio) and CBD (Central Business District) variables have the largest impact, of -37.38%~37.5%. From a practical perspective, the findings of this meta-analysis: 1) help refine contributing parameters in HPM studies to evaluate environmental economics; and 2) provide meaningful decision-making support for cost-effective remediation and benefit maximization.

Research on among individual variation in behavior has increased rapidly in recent years. It is intuitively appealing that among individual variation in behavior has ecological consequences and among the most likely to be affected is trophic niche. Bold individuals, with the tendency to be explorative and risk tolerant, can be less likely to alter their foraging behavior across contexts and therefore forage more consistently. Stable isotopes are a useful tool to retrospectively estimate ecological niche and have been found to correlate to foraging behavior in the wild. It is now pressing to extent studies to further examine the ecological or evolutionary relevance of personality. We examined if common behavioral traits were correlated to ecological niche in the wild using a rapid behavioral assay and δ13C and δ15N stable isotopes from fin and muscle reflecting ecological niche for the previous weeks and months. We found that latency to explore, as a proxy for boldness, correlated to values of δ13C with bolder fish having lower δ13C values. Moreover, latency to explore also explained variation in the change in individual stable isotope niche over time. These results highlight the long-term ecological importance of among individual variation in behavior and are among the first to support a correlation of laboratory measures of behavior and ecological niche in the wild.

Symphony to Leadless pacing – An Ode to JoyHassan Khan1, Larry A Chinitz1*1Leon H. Charney Division of Cardiology. New York University Langone Health. New York, NY, USA*Larry A Chinitz MD, FACC, FACP Benjamin and Coyle Family Professor of Medicine and Cardiac Electrophysiology Director, Cardiac Electrophysiology and the NYU Heart Rhythm CenterClinical Director, Leon H Charney Division of CardiologyNYU School of Medicine 212-263-7149 (O)larry.chinitz@nyumc.orgWord count, text: 1222 (excluding references) Number of tables/figures: 1COI; L.Chinitz- Speakers Honoraria; Medtronic,AbbottCoi; H. Khan- NoneLudwig van Beethoven’s 9th Symphony is regarded by many musicologists as one of the finest works in the history of music. It is notable for several reasons, particularly being the first example of a composer using voices, with words sung by a chorus and vocal soloist in the final movement. These words were adapted from the poem ”Ode to Joy”, written by Friedrich Schiller, and to date symbolize the celebration of music, making all who hear it feel better about life.Leadless pacing has also made a transformational effect on the lives of patients with bradyarrhythmias. Introduced to overcome the complications and adverse effects associated with conventional transvenous pacemakers, leadless pacing is observed to be safe, with a low risk of both short and long-term adverse events and high rates of successful implantation1, 2. To further the role of leadless pacing, the MARVEL (Micra Atrial TRacking Using a Ventricular AccELerometer) 23 prospective non-randomized multicenter clinical trial, tested the ability of an enhanced AV synchronous pacing algorithm utilizing the device’s three axis accelerometer, to attain mechanical sensing of atrial contractility. The MICRA AV TPS (Medtronic, MN) was released in 2020 with a ventricular pacing and atrial tracking mode (VDD), and achieved mechanical atrial sensing resulting in AV-synchronous pacing of >70% at rest in 95% participants (38 of the 40 with complete heart block) within the trial. Significant benefits to AV synchrony include avoidance of pacemaker syndrome, improvement of quality of life and as seen in these patients, improvement in left ventricle stroke volume and function3-5.The study observed that AV synchrony varied with physical activity and posture, with best results achieved at rest. Patient selection is crucial for optimal use of this algorithm as it is difficult to track atrial rates >105 bpm. At higher sinus rates, i.e. during exercise, the A3 and A4 signals fuse, along with encroachment of A4 on PVAB as the sinus rate increases further. Patient characteristics remain crucial and as seen in a subsidiary analysis of the MARVEL 2, individuals with markers of diastolic dysfunction (higher E/A ratios) and /or atrial myopathy (atrial strain) were found to be at higher risk of reduced mechanical atrial sensing of A46. Moreover, those with weak atrial contractions may not provide adequate A4 signals to the accelerometer. Therefore, performances of the algorithm in a real-world setting may not mirror those seen in the clinical trial arena. Further complicating the issue remains the ideal threshold for AV synchrony, which is assigned to >70% in research studies. In practice however, the AV synchrony cut-off required to achieve meaningful clinical benefit, avoid pacemaker syndrome and improve quality of life remains uncertain, though is certainly not 100%Recognizing that optimal AV synchrony in routine clinical practice may be challenging, Kowgli et al. in this issue of the Journal of Cardiovascular Electrophysiology , describe their multicenter institutional experience of outpatient programming optimization of the AV-synchronous MICRA leadless pacing system7. They included 43 patients with MICRA AV following exclusion of those with persistent atrial fibrillation or reduced follow-up. They describe the frequency of AV synchrony (defined as the ratio of atrial mechanically sensed (AM)-ventricular pacing to total ventricular paced percentage) at device interrogation done at 3 months of follow up. They report an overall mean AV synchronous pacing (AsVP) of 62.9%. In 65% of the patients adequate AV synchrony with AsVP >70% was found. Those with inadequate AsVP (<70%) had a higher body mass index, higher prevalence of congestive heart failure and prior history of cardiac surgery. Authors note that a small A4-wave amplitude, high ventricular pacing burden, and inadequate device reprogramming (over-use of auto A4 threshold, or lack of initiation of VDD mode at initialization) were main considerations for suboptimal AV synchronous pacing.Most importantly, their data confirms and is in line with recent reports,8, 9 that the success in achieving AV synchrony in a real-world setting may be lower than the MARVEL 2 clinical trial. The results also emphasize the importance of active programming changes which can significantly improve AV synchrony following an optimization post implantation. As identified in this report, MICRA AV optimization may require a learning curve, noted by an improvement in AsVP from 55% earlier, to 68% later in the study. Critical programming changes made by performing a manual atrial mechanical (MAM) test while disabling the features that automatically affect these, include adjusting the post ventricular atrial blanking (PVAB), A3/A4 windows and A3/A4 thresholds, and turning off the AV conduction mode (VVI +) in those with complete heart block and escape >40 bpm. The authors and others8, 9 have identified helpful examples of troubleshooting these interval timings and thresholds for optimizing AV synchrony, which an implanter must be familiar with in order to successfully manage patients with leadless AV synchronous devices. Critically, while performing a MAM test, a key prerequisite for successful interpretation of device tracings is the inclusion of an optimal ECG tracing. In cases where standard leads do not show a discernable P wave, the Lewis lead method can be helpful10. Several key steps towards successful optimization of AV synchrony are summarized in Figure 1.Kowgli et al. evaluated AV synchrony at device interrogation 3 months post implant whereas MARVEL 2 limited the analysis duration to about 30 minutes immediately after pacemaker optimization. This is a somewhat artificial setting and would be expected to be different from observations made at 3 months and longer periods of follow-up. Real world settings are also associated with changes in heart rate, patient movement, atrial or ventricular arrhythmias, as well as changes in lifestyle and medications. Therefore, an optimization session both at post-op (prior to discharge) and in the clinic at follow-up, with prior Holter monitoring and exercise testing in younger patients, may help detect AV dysynchrony earlier and allow recognition and correction of atrial mechanical under or oversensing.The current study acknowledges the complexity of leadless pacing and the need for optimization at follow-up to achieve higher levels of AV synchrony. It also reflects on patient selection being crucial to reap the full benefits of leadless technology. In patients with fast baseline sinus rates, in younger and physically active patients, or those who may have a greater reliance on AV synchrony at peak heart rates, this device may not be optimal. In addition, P wave amplitude, frequent atrial and ventricular arrhythmias, and sinus bradycardia will adversely affect the ability to achieve AV Synchrony. With appropriate patient selection, monitoring and best practices of device programming, leadless pacemakers will undoubtedly achieve clinically relevant AV synchrony. The true marvel of leadless technology can be seen as an impressive reduction in complication rates and better patient satisfaction compared to current transvenous devices. Further improvements in design, technology and best practices will deliver symphony to pacing and afford those who use it an experience that is safe and reminiscent of normal cardiovascular physiology.

Land degradation and desertification (LDD) has become one of the most urgent global environmental issues. The complexity of LDD make it difficult to quantify, how to monitor quickly and accurately has become the key to realize the sustainability for land resources. To achieve this target, firstly, a comprehensive index—land degradation and desertification status index (LDDSI) is built, which integrates the information in fractional vegetation cover (FVC), net primary productivity (NPP), albedo and modified temperature vegetation drought index (MTVDI) based on the spatial principal component analysis (SPCA). Then, identifies LDD from dynamics of land degradation and desertification status (LDDS) in 2001-2018. Based on this, we analyze the spatio-temporal process and driving mechanism of LDD in Northern China. The result indicates that: (a) LDDSI has a better monitoring performance, (b) LDD has been effectively alleviated, but the spatial distribution of LDDS maintains a high clustering pattern, which is difficult to be broken, (c) LDD in local regions is further expanded (1.75%) affected by many factors, which deserves our attention, and (d) the differences in climate, environmental backgrounds and human activities play a key role in LDDS and LDD. In addition, we assess the effectiveness of ecological projects implemented by the Chinese government. The current understanding in the change pattern and influencing mechanism for LDDS and LDD can provide a scientific basis for formulating ecological policies based on local conditions.

Purpose: Our study aimed to examine the impacts of blood cardioplegia (BC) and del Nido cardioplegia (DNC) solutions, which we used in isolated coronary artery bypass grafting, on early mortality and major adverse events. Material and method: We retrospectively analyzed 329 consecutive patients who underwent coronary artery bypass grafting (CABG) operations in our clinic between January 2016 and January 2020. Myocardial infarction, reoperation, cardiac tamponade, stroke, renal failure, extracorporeal membrane oxygenator requirement, and cardiopulmonary resuscitation were defined as major adverse events. The group for which del Nido cardioplegia was used was named Group D, and the group for which blood cardioplegia was used was named Group B. Group D consisted of 181 (55%) patients, and Group B consisted of 141 (45%) patients. Results: No statistically significant difference was determined between the groups regarding age, weight, body surface area, gender, or EuroSCORE ( p=.615, p=.560, p=.934, p=.365, p=.955, respectively). Although there was no statistically significant difference between the groups in terms of aortic cross-clamp time ( p=.712), the cardiopulmonary bypass duration was longer in Group B ( p=.001). Even though the incidence of stroke was higher in Group B ( p=.030), no statistically significant difference was observed between the groups regarding the total incidence of major adverse events, mortality, mechanical ventilation time, length of stay in the intensive care unit, or length of hospital stay ( p=.153, p=.130, p=.689, p=.710, p=.613, respectively). Conclusion: We found no significant difference in MAE, mortality, duration of MV, ICU stay, or hospitalization in the DNC and BC groups. We believe that both solutions can be used safely for cardiac protection in the adult patient population.

*Co-first authorsAbstract:Zearalenone (ZEA), one of the most prevalent estrogenic mycotoxins, contaminates crops, including maize, rice, and wheat. Previous studies have found high levels of mycotoxins, particularly fumonisin B1 (FB1) and aflatoxin B1 (AFB1) in maize from Guatemala. In addition, our group has reported high levels of serum aflatoxin B1 (AFB1) in this population. However, exposure to ZEA has not been examined in Guatemala. Thus, this pilot study assessed the presence of ZEA in urine samples from Guatemala City and vicinity (n=50). In addition, correlation between ZEA and AFB1was examined as well as correlations with maize and tortilla consumption. Ten of the 50 samples had detectable levels of ZEA, with a median level of 2.0 pg/uL. No correlations were found with AFB1 levels, nor with maize or tortilla consumption. This is the first report on the presence of ZEA in urine samples from Guatemala. These results suggest that further research on ZEA in Guatemala is warranted.

Heterogeneity in riverine habitats acts as a template for species evolution that influences river communities at different spatio-temporal scales. Although birds are conspicuous elements of these communities, the roles of phylogeny, functional traits and habitat character in their niche-use or species’ assembly have seldom been investigated. We explored these themes by surveying multiple headwaters over 3000 m of elevation in the Himalayan Mountains of India where specialist river birds reach their greatest diversity on Earth. After ordinating community composition, species traits and habitat character, we investigated whether river-bird traits varied with elevation in ways that were constrained or independent of phylogeny, hypothesising that trait patterns reflect environmental filtering. Community composition and trait representation varied strongly with elevation and river naturalness as species that foraged in the river/riparian ecotone gave way to small insectivores with obligate links to the river channel. These trends were influenced strongly by phylogeny as communities became more clustered by functional traits at higher elevation. Phylogenetic signals varied among traits, however, and were reflected in body mass, bill size and tarsus length more than in body size, tail length and breeding strategy. These variations imply that community assembly in high altitude river birds reflects a blend of phylogenetic constraint and habitat filtering coupled with some proximate niche-based moulding of trait character. We suggest that the regional co-existence of river birds in the Himalaya is facilitated by the same array of factors that together reflect the highly heterogeneous template of river habitats provided by these mountain headwaters.

Chronic obstipation complaints are among the most common health disorders worldwide, with a prevalence of up to 20%, increasing with age and affecting women significantly more often than men. Neurological disorders are the cause in about 12% of these cases, often aggravated by the inevitably potent medication for these conditions. The management of these cases is the subject of this study report. Its outcome dispels prejudice and warns of malpractice in an area where the symptom burden of patients is often very high, multifaceted, and disabling. Finding the most reliable and safe method to ameliorate chronic constipation, which is often painful and causing hemorrhoids, is therefore the key to an overall improvement in the quality of life of these patients.

Context Medical interns find prescribing challenging and lack readiness when commencing work. Error rates remain high despite education, supervision and pharmacists’ contributions. Feedback on prescribing may improve performance. Yet, work-based prescribing feedback focuses on rectifying errors. We aimed to improve prescribing using a theory-informed feedback intervention. Methods In this mixed methods study, we designed and implemented a feedback intervention, informed by Feedback-Mark 2 Theory. Interns commencing internal medicine terms engaged in the intervention. Prescribing performance was evaluated by comparing the number of errors per order of at least 30 medication orders per prescriber from weeks 1-3 (pre/baseline) and weeks 8-9 (post-intervention). Baseline interns’ audit findings were analysed and discussed during individualised feedback sessions with either a clinical pharmacologist (Site 1) or pharmacist educator (Site 2). Results Prescribing by 88 interns, across two hospitals over five 10 week terms, was analysed. Following the intervention, there was a significant reduction in prescribing errors (p<0.001) from 1598 errors in 2750 initial orders (median [IQR] 0.48 [0.35-0.67] errors per order) before and 1113 errors in 2694 orders (median [IQR] 0.30 [0.17-0.50] errors per order) after. There was no reduction in initial error rate over the five terms. Conclusions Our theory-informed feedback intervention contributed to a significant reduction in interns’ prescribing errors. This study opens up new strategies for improving prescribing safety through feedback interventions. The results emphasise that learner centred and improvement-focussed feedback with an agreed plan could significantly improve prescribing safety an outcome which supervision, education and pharmacist interventions had not delivered.

Human activities can degrade the quality of coral reefs, cause a decline in fish species richness and functional diversity and an erosion of the ecosystem services provided. Environmental DNA metabarcoding (eDNA) has been proposed as an alternative to Underwater Visual Census (UVC) to offer more rapid assessment of marine biodiversity to meet management demands for ecosystem health indices. Taxonomic information derived from sequenced eDNA can be combined with functional traits and phylogenetic positions to generate a variety of ecological indices describing ecosystem functioning. Here, we inventoried reef fish assemblages of two contrasted coastal areas of Curaçao, (i) in close proximity to the island’s capital city and (ii) in a more remote area under more limited anthropogenic pressure. We sampled eDNA by filtering large volumes of sea water (2 x 30L) along 2km boat transects, which we coupled with species ecological properties related to habitat use, trophic level and body size to investigate the difference in fish taxonomic composition, functional and phylogenetic indices recovered from eDNA metabarcoding between these two distinct coastal areas. Despite no marked difference in species richness, we found a higher phylogenetic diversity in proximity to the city, but a higher functional diversity on the more isolated reef. Composition differences between coastal areas were associated with different frequencies of reef fish families. Because of a partial reference database, eDNA only partly matched those detected with UVC, but eDNA surveys nevertheless provided rapid and robust species occupancy responses to contrasted environments. eDNA metabarcoding coupled with functional and phylogenetic diversity assessment can serve the management of coastal habitats under increasing threat from global changes.

Rhodococcus hoagii infection is associated with exposure to farm animals but, in the present case, the patient had not left her urban environment. The immunocompromised female patient presented bloodstream infection by an organism that defied straightforward diagnosis and her life was saved only by a timely change in antibiotic therapy.

When redness of the auricle is present, the main differential diagnoses are erysipelas, Ramsay-Hunt syndrome, relapsing polychondritis, and chilblain lupus. The pathogenesis of red ears can be inferred by careful anatomical observation. Making the correct diagnosis is important because the treatment and prognosis vary according to the cause.

The taxine alkaloids within the seeds, leaves and bark of the Yew Tree can cause death via antagonising cardiac Ca2+ channels. We report the case of a 17-year-old male who presented with severe cardiogenic shock with biventricular block following the consumption of Yew Tree seeds that he had purchased online.

In resource-constrained settings, mucopolysaccharidosis (MPS) is a rare hereditary metabolic illness that frequently remains undiagnosed. We present a scenario that illustrates the challenges in diagnosing and managing MPS due to test inaccessibility, as well as potential approaches to minimize the hurdles.

The recently developed Edge Tracing (ET) method allows to estimate the radial deformation in axisymmetric tensile specimens via analysis of digital images recorded during the experiments. Images are processed to detect the sample’s contours and therefore, estimate the minimal cross–section diameter. This technique was mainly developed to characterize the elastic–plastic behavior well beyond the necking strain. The aim of this work is to extend the ET method to two case studies. Firstly, the post–necking behavior and failure of a low ductility Al–alloy are investigated. Low ductility alloys tend to fail brutally after reaching the maximum load. The major result is the capture of the sharp load drop which allowed to calibrate parameters of a GTN damage model. Secondly, the anisotropic elastic–plastic behavior of a “vintage” line pipe steel is characterized by a direct measurement of the Lankford coefficient. Assembled experimental data allowed to model the anisotropic plasticity in different loading directions.

Developing on-site biomarker enrichment platforms could help to improve the diagnosis of gastrointestinal (GI) tract diseases at early stages.  Medical procedures, such as colonoscopies and imaging techniques, are used to diagnose disease, but are not easily accessible for repeat measurements. In the other hand, liquid biopsies, e.g., blood, urine, or fecal samples, have become important sampling strategies to identify health concerns.  Herein, a robotic pill is designed for collecting relevant biomarkers from the GI over prolonged sampling periods. The robotic pill comprises a magnetic core for locomotion, a delayed gate mechanism that controls sampling location based on changes in its environment, and an enrichment module that traps biomarkers in an absorbent matrix while enabling biofluid to pass through the chamber. The robotic pill was assessed to sample microparticles, proteins, and bacteria from solution. Moreover, the robotic pill was capable of directed locomotion in complex environments and docking in a targeted region against fluid flow. Utilization of an untethered robotic sampling system could provide a tool to investigate aspects of disease initiation and progression for early diagnosis and therapy monitoring.

We recently published a paper quantifying the genome-wide consequences of natural selection, including the effects of indirect selection due to the correlation of genetic regions (neutral or selected) with directly selected regions (Gompert et al. 2022). In their critique of our paper, Charlesworth & Jensen (2022) make two main points: (i) indirect selection is equivalent to hitchhiking and thus well documented (i.e., our results are not novel), and (ii) that we do not demonstrate the source of linkage disequilibrium (LD) between SNPs and the Mel-Stripe locus in the Timema cristinae experiment we analyze. As we discuss in detail below, neither of these are substantial criticisms of our work.