While both the incidence and general awareness of food allergies is increasing, the variety and clinical availability of therapeutics remain limited. Therefore, investigations into the potential factors contributing to the development of food allergy and the mechanisms of natural tolerance or induced desensitization are required. In addition, a detailed understanding of the pathophysiology of food allergies is needed to generate compelling, enduring, and safe treatment options. New findings regarding the contribution of barrier function, the effect of emollient interventions, mechanisms of allergen recognition, and the contributions of specific immune cell subsets through rodent models and human clinical studies provide novel insights. With the first approved treatment for peanut allergy, the clinical management of food allergy is evolving towards less intensive, alternative approaches involving fixed doses, lower maintenance dose targets, co-administration of biologicals, adjuvants, and tolerance-inducing formulations. The ultimate goal is to improve immunotherapy and develop precision-based medicine via risk phenotyping allowing optimal treatment for each food-allergic patient.

Health professions education is in constant pursuit of new ways of teaching and assessment in order to improve the training of healthcare professionals. Educators are often challenged with designing, implementing, and evaluating programs in the context of their professional practice, particularly those in response to dynamic and emerging social needs. This article explores the synergies and intersections of two approaches -- quality improvement and program evaluation -- and the potential utility of their combinations within our field to design, evaluate, and most importantly, improve educational programming. We argue that the inclusion of established quality improvement frameworks within program evaluation provides a proven mechanism for driving change, can optimize programming within the multi-contextual education systems, and, ultimately, that these two approaches are complementary to one another. These combinations hold great promise for optimizing programming in alignment with social missions, where it has been difficult for institutions worldwide to generate and capture evidence of social accountability.

Dispersal is a crucial mechanism to living beings, allowing them to reach new resources such that populations and species can explore new environments. However, directly observing the dispersal mechanisms of widespread species can be costly or even impracticable, which is the case for mangrove trees. The influence of ocean currents on the mangroves’ propagules’ movement has been increasingly evident; however, few studies mechanistically relate the patterns of population distribution with the dispersal by oceanic currents under an integrated framework. Here, we evaluate the role of oceanic currents on dispersal and connectivity of Rhizophora mangle along the Southwest Atlantic. We inferred population genetic structure and migration rates based on single nucleotide polymorphisms, simulated the displacement of propagules along the region and tested our hypotheses with Mantel tests and redundancy analysis. We observed a two populations structure, north and south, which is corroborated by other studies with Rhizophora and other coastal plants. The inferred recent migration rates do not indicate gene flow between the sampled sites. Conversely, long-term migration rates were low across groups and contrasting dispersal patterns within each one, which is consistent with long-distance dispersal events. Our hypothesis tests suggests that both isolation by distance and isolation by oceanography (derived from the oceanic currents) can explain the neutral genetic variation of R. mangle in the region. Our findings expand current knowledge of mangrove connectivity and highlight how the association of molecular methods with oceanographic simulations improve the interpretation power of the dispersal process, which has ecological and evolutionary implications.

In many farming landscapes, aquatic features such as wetlands, creeks and dams provide water needed for stock and irrigation, while also acting as habitat for a range of plants and animals. Indeed, some species threatened by land use change may otherwise be considerably rarer – or even extinct – in the absence of these habitats. Therefore, a critical issue for the maintenance of biodiversity in agricultural landscapes is the extent to which the management of aquatic systems can help promote the integration of agricultural production and biodiversity conservation. We completed a snapshot cross-sectional study in southern New South Wales (south-eastern Australia) to quantify the efficacy of simple management practices – partial revegetation and stock reduction via fencing – for improving vegetation structure, water quality, and macroinvertebrate assemblages. We found that even short-term livestock exclusion resulted in increased vegetation cover. Relative to dams that were unfenced, those that had been partially or completely fenced for many years were characterized by reduced turbidity and nutrient levels and contained fewer thermotolerant (faecal) coliforms. They also supported increased richness and abundance of macroinvertebrates. In contrast, control (unfenced) dams tended to have high abundance of a few macroinvertebrate taxa. Notably, differences remained between the macroinvertebrate assemblages of fenced dams and nearby ‘natural’ waterbodies. Our results show how management interventions can improve water quality in farm dams and provide a valuable reference and baseline for longer term studies of farm dam improvement.

Introduction. In this prospective multicenter analysis, we aimed to investigate the predictive role of neutrophil/lymphocyte ratio (NLR) in permanent pacemaker implantation (PPI) in patients undergoing transcatheter aortic valve replacement (TAVR). Material and methods. 179 consecutive patients without previous PPI underwent TAVR from February 2017 to September 2021. Patients were further divided based on presence (n=48) and absence of conduction abnormalities (CAs) at hospital admission (n=131). Results . In patients with previous CAs, NLR values did not differ significantly between patients requiring PPI (n=16, 33%) and those not requiring it. In contrast, in patients with no CAs at hospital admission, NLR values measured at admission and on TAVR day were significantly higher in patients requiring PPI (n=17, 13%) (4.07±3.22 vs 3.01±1.47, p=0.025, and 10.81±7.81 vs 5.84±3.78, p=0.000, respectively). Multivariable analysis showed that NLR at TAVR day was an independent predictor of PPI in patients without CAs (OR 1.294; 95% CI 1.028-1.630; p=0.028), but not in those with previous CAs. ROC curve analysis showed that the cut point was a NLR value of >7.25. Time to PPI was delayed till 21 days in patients without CAs. Conclusions. In this prospective study, higher NLR values on the day of TAVR day were associated with an increased PPI rate in patients undergoing TAVR with no previous CAs. It is advisable, being inflammation part of the process, to prolong the time of observation for all patients without CAs till at least 21 days not to miss any new CA necessitating PPI.

Abstract Background: Effectiveness of hydroxyurea (HU) in SCD is well established. Unanswered questions persist about use in African children in terms of acceptability and monitoring. We determined real-life user-barriers, safety and effects of therapy among children using HU in Nigeria. Methods: We retrieved and reviewed case notes of children on hydroxyurea (10-15mg/kg/day followed by dose escalation) from January 2017 to June 2019, checked for adherence to drugs, clinics and laboratory tests; starting dose, toxicity and benefits (hematologic, clinical, parental satisfaction). A questionnaire complemented case note findings. Results 116 patients received hydroxyurea (mean dose of 18 mg/kg/ day). Improvement in general well-being was 91.25%, reduction in bone pain 83.3%, hospital admissions 71.9%, abdominal pain 62.3%, blood transfusion 56.1%. Sixteen percent voluntarily stopped HU because of cost and side effects. Sixty-seven percent of parents complained about daily drug use, frequency and cost of monitoring. Adherence to daily HU was 88.8%, doctor’s appointments 22.8%, hematology tests 17.5%, organ function 32.5%. Five patients had mild neutropenia. No significant hepatic or renal toxicity occurred. Common side effects were abdominal pain (18.4%) and headache (13.2%). Significant increase in hemoglobin, fetal hemoglobin, MCV and reduction in absolute neutrophil counts occurred. Conclusion: Hydroxyurea at 10-15mg/kg/day is safe, effective and acceptable to parents. Monitoring is challenging. Care-giver education, support services, staff training, HU clinics may improve utilization. HU protocols that reduce monitoring and yet provide good clinical and laboratory benefits are necessary. This study adds to the implementation science strategies that is needed to increase HU use in Nigeria.

African swine fever (ASF) is one of the most important viral diseases of domestic pigs and wild boar. Apart from endemic cycles in Africa, ASF is now continuously spreading in Europe and Asia. As ASF leads to severe but unspecific clinical signs and high lethality, early pathogen detection is of utmost importance. Recently, “point-of-care” (POC) tests have been intensively discussed for the use in remote areas but also in the context of on-farm epidemiological investigations and wild boar carcass screening. Along these lines, the INGEZIM ASFV CROM Ag lateral flow assay (Eurofins Technologies Ingenasa) promises virus antigen detection under field conditions within minutes. In the present study, we evaluated the performance of the assay with selected high-quality reference blood samples, and also with real field samples from wild boar carcasses in different stages of decay from the ongoing ASF outbreak in Germany. While we observed a sensitivity of roughly 77% in freeze-thawed matrices of close to ideal quality, our approach to simulate field conditions in direct carcass testing without any modification resulted in a drastically reduced sensitivity of only 12.5%. Freeze thawing increased the sensitivity to roughly 44% which mirrored the overall sensitivity of 49% in the total data set of carcass samples. A diagnostic specificity of 100% was observed. However, most of the German ASF cases in wild boar would have been missed using the lateral flow assay (LFA) alone. Therefore, the antigen-specific LFA should not be regarded as a substitute for any OIE listed diagnostic method and has very limited use for carcass testing at the point of care. For optimized LFA antigen tests, the sensitivity with field samples must be significantly increased. An improved sensitivity is seen with freeze-thawed samples, which may indicate problems in the accessibility of ASFV antigen.

Aims: In order to better predict the pharmacokinetics (PK) of antibodies in children, and to facilitate dose optimization of antibodies in pediatric patients, there is a need to develop systems PK models that integrate ontogeny related changes in human physiological parameters. Methods: A population-based physiological-based PK (PBPK) model to characterize antibody PK in pediatrics has been developed, by incorporating age-related changes in body weight, organ weight, organ blood flow rate, and interstitial volumes in a previously published platform model. The model was further used to perform Monte Carlo simulations to investigate clearance vs. age and dose-exposure relationship for infliximab. Results: By estimating only one parameter and associated interindividual variability, the model was able to characterize clinical PK of infliximab from two pediatric cohorts (n=141, 4-19 years) reasonably well. Model simulations demonstrated that only 50% of children reached desired trough concentrations when receiving FDA-labelled dosing regimen for infliximab, suggesting that higher doses and/or more frequent dosing are needed to achieve target trough concentrations of this antibody. Conclusion: The pediatric PBPK model presented here can serve as a framework to characterize the PK of antibodies in pediatric patients. The model can also be applied to other protein therapeutics to advance precision medicine paradigm and optimize antibody dosing regimens in children.

Spatial isolation is a key driver of population-level variability in traits and genotypes worldwide. Geographical distance between populations typically increases isolation, but organisms face additional environmental barriers when dispersing between suitable habitat patches. Despite the predicted universal nature of the causes of isolation, global comparisons of isolation effects across taxa and geographic systems are few. We assessed the strength of isolation due to geographic and macroclimatic distance for paired marine island and paired mainland populations within the same species. Our meta-analysis included published measurements of phenotypic traits and neutral genetic diversity from 1832 populations of 112 plant and animal species at a global scale. As expected, phenotypic differentiation was higher between marine islands than between populations on the mainland, but spatial patterns of neutral genetic diversity did not vary between the two systems. Geographic distance had comparatively weak effects on the spatial patterns of phenotypes and neutral genetic diversity, but only phenotypic trait variability showed signal of system-dependence. These results suggest that spatial patterns of phenotypic variation are determined by system-dependent eco-evolutionary pressures, while the spatial variability of neutral genetic diversity might be universal. Our approach demonstrates that global biodiversity models that include island biology studies may progress our understanding of the interacting effects of spatial habitat structure, geographic- and environmental distances on biological processes underlying spatial population variability. We formulate future research directions for empirical tests and global syntheses in the field.

Normal Mode Analysis is a fast and inexpensive approach that is largely used to gain insight into functional protein motions, and more recently to create conformations for further computational studies. However, when the protein structure is unknown, the use of computational models is necessary. Here, we analyze the capacity of normal mode analysis in internal coordinate space to predict protein motion, its intrinsic flexibility and atomic displacements, using protein models instead of native structures, and the possibility to use it for model refinement. Our results show that normal mode analysis is quite insensitive to modelling errors, but that calculations are strictly reliable only for very accurate models. Our study also suggests that internal normal mode analysis is a more suitable tool for the improvement of structural models, and for integrating them with experimental data or in other computational techniques, such as protein docking or more refined molecular dynamics simulations.

Paravalvular leak (PVL) is uncommon but can lead to severe complications after surgical or transcatheter aortic valve replacement. Clinical complications such as heart failure, haemolysis and infective endocarditis can be catastrophic results if not treated in promptly. It is, therefore, vital that PVLs are diagnosed early using various imaging modalities. Different approaches have been studies in managing PVL’s; of late, there is an increased interest in the use of minimally invasive procedures such as the transcatheter aortic valve closure procedure due to the decreased occurrence of further operations. This review discusses the classification of PVLs, diagnostic approaches and the available management options.

Sarcophaga peregrina is usually considered to be of great ecological, medical and forensic significance, and has the biological characteristics such as the ovoviviparous reproductive pattern and adaptation to feed on carrion. However, the underlying mechanisms still remain unsolved by lack of high-quality genome. Here we present de novo–assembled genome at chromosome-scale for S. peregrina. The final assembled genome was 560.31 Mb with contig N50 of 3.84 Mb. Hi-C scaffolding reliably anchored six pseudochromosomes, accounting for 97.76% of the assembled genome. Moreover, 45.70% of repeat elements were identified in the genome. A total of 14,476 protein-coding genes were functionally annotated, accounting for 92.14% of all predicted genes. Phylogenetic analysis indicated that S. peregrina and S. bullata diverged ~7.14 Mya. Comparative genomic analysis revealed expanded and positively selected genes related to biological features that aid in clarifying its ovoviviparous reproduction and necrophagous habit, such as horionic membrane formation and Dorso-ventral axis formation, lipid metabolism, and olfactory receptor activity. This study provides a valuable genomic resource of S. peregrina, and sheds insight into further revealing the underlying molecular mechanisms of adaptive evolution.

Introduction The rapid spread of the pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)(COVID-19) virus resulted in governments around the world instigating a range of measures, including mandating the wearing of face coverings on public transport/in retail outlets. Methods We developed a sequential assessment of risk reduction provided by face coverings using a step-by-step approach. The United Kingdom Office of National Statistics(ONS) Population Survey data was utilised to determine the baseline total number of community-derived infections. These were linked to reported hospital admissions/hospital deaths to create case admission risk ratio/admission-related fatality rate. Results Overall, we show that only 7.3% of all community-based infection risk associates with public transport/retail outlets. The reported weekly community infection rate was 29,400 new cases at the start (24th July). The rate of growth in hospital admissions and deaths for England was around -15%/week, suggesting the infection rate, R, in the most vulnerable populations was just above 0.8. In this situation, average infections over the evaluated 13week follow-up period was 9,517/week. With face covering of 40% effectiveness, this reduced average infections by 844/week, hospital admissions by 8/week and deaths by 0.6/week; a fall of 9% over the period total. If, however, the R-value rises to 1.0, then average community infections would stay at 29,400/week and face coverings could reduce average weekly infections by 3,930, hospital admissions by 36 and deaths by 2.9/week; a 13% reduction. These reductions should be seen in the context of 102,000/week all-cause hospital emergency admissions in England and 8,900 reported deaths in the week ending 7thAugust 2020. Conclusion We have illustrated that the policy on mandation of face coverings in retail outlets/on public transport may have limited value in reducing hospital admissions/deaths. Impact appears small compared to all other sources of risk, thereby raising questions regarding effectiveness of the policy.

Underpinnings of the distribution of allopolyploid species (hybrids with duplicated genome) along spatial and ecological gradients are elusive. As allopolyploid speciation combines the range of genetic and ecological characteristics of divergent diploids, allopolyploids initially show their additivity and are predicted to evolve differentiated ecological niches to establish in face of their competition. Here, we use four diploid wild wheats that differentially combined into four independent allopolyploid species to test for such additivity and assess the impact of ecological constraints on species ranges. Divergent genetic variation from diploids being fixed in heterozygote allopolyploids supports their genetic additivity. Spatial integration of comparative phylogeography and modeling of climatic niches supports ecological additivity of locally adapted diploid progenitors into allopolyploid species which subsequently colonized wide ranges. Allopolyploids fill suitable range to a larger extent than diploids and conservative evolution following the combination of divergent species appears to support their expansion under environmental changes.

Objectives. The aim of this systematic review is to assess the effects of community pharmacist-led interventions to optimize the use of antibiotics and identify which interventions are most effective. Methods. This review was conducted according to the PRISMA-P guidelines (PROSPERO: CRD42020188552). PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were searched for (randomised) controlled trials. Included interventions were required to target antibiotic use, be set in the community pharmacy context and be pharmacist-led. Primary outcomes were quality of antibiotic supply and adverse effects while secondary outcomes included patient reported outcomes. Risk of bias was assessed using the ‘Cochrane suggested risk of bias criteria’ and narrative synthesis of primary outcomes conducted. Results. Seventeen studies were included covering in total 3,822 patients (mean age 45.6 years, 61.9% female). Most studies used educational interventions. Three studies reported on primary outcomes, twelve on secondary outcomes and two on both. Three studies reported improvements in quality of dispensing where interventions led to more intensive symptom assessment and a reduction of OTC or wrong choice antibiotic supply. Some interventions led to higher consumer satisfaction, effects on adherence were mixed. All studies had unclear or high risks of bias across at least one domain, with large heterogeneity between studies. Conclusions. Our review suggests some possible positive results from pharmacist-led interventions, but the role of the pharmacist needs to be expanded. This review should be interpreted as exploratory research, as more high-quality research is needed. Authors did not receive funding for the review.

Background – The impact of post-operative complications on long-term survival is not well characterized. We sought to study the prevalence of post-operative complications after cardiac surgery and their impact on long-term survival. Methods – Operative survivors (n=26,221) who underwent coronary artery bypass grafting (CABG) (n=13054, 49.8%), valve surgery (n=8667, 33.1%) or combined CABG and valve surgery (n=4500, 17.2%) from 1993 to 2019 were included in the study. Records were reviewed for post-operative complications and long-term survival. The associations between post-operative complications and survival were assessed using a Cox-proportional model. Results – Complications occurred in 17,463 (66.6%) of 26,221 operative survivors. A total of 17 post-operative complications were analyzed. Post-operative blood product use was the commonest (n=12397, 47.3%), followed by atrial fibrillation (n=8399, 32.0%), prolonged ventilation (n=2336, 8.9%), renal failure (n=870, 3.3%), re-operation for bleeding (n=859, 3.3%) and pacemaker/ICD insertion (n=795, 3.0%). Stroke (HR 1.55, 95%CI 1.36-1.77), renal failure (HR 1.45, 95% CI 1.33-1.58) anticoagulant-related events (HR 1.26, 95%CI 1.02-1.56) and pneumonia (HR 1.23, 95%CI 1.11-1.36) had the strongest impact on long-term survival. Long-term survival decreased as the number of post-operative complications increased. Conclusions – Post-operative complications after cardiac surgery significantly impact outcomes that extend beyond the post-operative period. The presence, number and type of post-operative complications adversely impact long-term survival. Stroke, renal failure, anticoagulant-related events and pneumonia are particularly associated with poor long-term survival.

Product formulations for industrial processes are typically developed at lab-scale. However, the mixing conditions are not easily mimicked in the lab. A rotational device is proposed in this work as a fast lab-scale formulation development, which enables mimicking the mixing conditions in the industrial process. The geometrical configurations of the rotational device are from rheometry devices (plate-plate and cone-plate). The main advantages of this method are the small amounts of raw materials, and shorter testing times. This methodology is applied to an industrial case study, the Reaction Injection Moulding (RIM) process. The mixing length scales evolution in the rotational rheometer were matched to those in RIM machines. The main novelty of this work is the introduction of a protocol that bridges the processing conditions at lab using small amounts of raw materials to high throughput continuous flow reactors.

Background: The success of subcutaneous immunotherapy (SCIT) mostly depends on regular injections. Our aim was to investigate adherence to SCIT with aeroallergens during the COVID-19 pandemic and demonstrate clinical consequences of treatment disruptions in real-life. Methods: Visual analogue scale for quality of life (VAS-QoL), VAS for symptom scores (VAS-symptom), medication scores (MSs) and total symptom scores (TSS-6) were recorded during the pandemic in 327 adult allergic rhinitis and/or asthmatic patients receiving maintenance SCIT and these scores were compared with the pre-pandemic data. Patients were grouped according to SCIT administration intervals; no delay (Group 1), <2 months (Group 2), and ≥2 month intervals (Group 3). Results: 104 (31.8%) patients (Group 3) were considered as non-adherent which was mostly related to receiving SCIT with HDMs and using public transportation for reaching the hospital. Median MS, VAS-symptom and TSS-6 scores of Group 3 patients during the pandemic were higher than the pre-pandemic scores (p=0.005, p<0.001, p<0.001, respectively) whereas median VAS-QoL scores of Group 3 during the pandemic were lower than the pre-pandemic scores (p<0.001). Median TSS-6 and VAS-symptom scores were the highest in Group 3 compared to other groups (p<0.001 for each comparison). Median VAS-QoL scores were the lowest in Group 3 compared to Group 1 and Group 2 (p<0.001, p=0.043, respectively). Conclusion: When precautions in allergy clinics are carefully applied, adherence to SCIT can be high during a pandemic. Patients must be warned about adhering to SCIT injections since delays in SCIT administration can deteriorate clinical symptoms.