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Schools are high-risk settings for infectious disease transmission. Wastewater monitoring for infectious diseases has been used to identify and mitigate outbreaks in many near-source settings during the COVID-19 pandemic, including universities and hospitals but less is known about the technology when applied for school health protection. This study aimed to implement a wastewater surveillance system to detect SARS-CoV-2 and other public health markers from wastewater in schools in England.

Objectives To determine the test-retest reproducibility and observer variability of CMR-derived LA function, using (i) LA strain (LAS) and strain rate (LASR), and (ii) LA volumes (LAV) and emptying fraction (LAEF). Methods Sixty participants with and without cardiovascular disease (aortic stenosis (AS) ( n = 16), type 2 diabetes (T2D) ( n = 28), end-stage renal disease on haemodialysis ( n = 10) and healthy volunteers ( n = 6)) underwent two separate CMR scans 7–14 days apart. LAS and LASR, corresponding to LA reservoir, conduit and contractile booster-pump function, were assessed using Feature Tracking software (QStrain v2.0). LAEF was calculated using the biplane area length method (QMass v8.1). Both were assessed using 4- and 2-chamber long-axis standard steady-state free precession cine images, and average values were calculated. Intra- and inter-observer variabilities were assessed in 10 randomly selected participants. Results The test-retest reproducibility was moderate to poor for all strain and strain rate parameters. Overall, strain and strain rate corresponding to reservoir phase (LAS_r, LASR_r) were the most reproducible, yielding the smallest coefficient of variance (CoV) (29.9% for LAS_r, 28.9% for LASR_r). The test-retest reproducibility for LAVs and LAEF was good: LAVmax CoV = 19.6% ICC = 0.89, LAVmin CoV = 27.0% ICC = 0.89 and total LAEF CoV = 15.6% ICC = 0.78. The inter- and intra-observer variabilities were good for all parameters except for conduit function. Conclusion The test-retest reproducibility of LA strain and strain rate assessment by CMR utilising Feature Tracking is moderate to poor across disease states, whereas LA volume and emptying fraction are more reproducible on CMR. Further improvements in LA strain quantification are needed before widespread clinical application. Key Points • LA strain and strain rate assessment using Feature Tracking on CMR has moderate to poor test-retest reproducibility across disease states. • The test-retest reproducibility for the biplane method of assessing LA function is better than strain assessment, with lower coefficient of variances and narrower limits of agreement on Bland-Altman plots. • Biplane LA volumetric measurement also has better intra- and inter-observer variability compared to strain assessment.

Malaria causes about half a million deaths annually, with Plasmodium falciparum being responsible for 90% of all the cases. Recent reports on artemisinin resistance in Southeast Asia warrant urgent discovery of novel drugs for the treatment of malaria. However, most bioactive compounds fail to progress to treatments due to safety concerns. Drug repositioning offers an alternative strategy where drugs that have already been approved as safe for other diseases could be used to treat malaria. This study screened approved drugs for antimalarial activity using an in silico chemogenomics approach prior to in vitro verification. All the P. falciparum proteins sequences available in NCBI RefSeq were mined and used to perform a similarity search against DrugBank, TTD and STITCH databases to identify similar putative drug targets. Druggability indices of the potential P. falciparum drug targets were obtained from TDR targets database. Functional amino acid residues of the drug targets were determined using ConSurf server which was used to fine tune the similarity search. This study predicted 133 approved drugs that could target 34 P. falciparum proteins. A literature search done at PubMed and Google Scholar showed 105 out of the 133 drugs to have been previously tested against malaria, with most showing activity. For further validation, drug susceptibility assays using SYBR Green I method were done on a representative group of 10 predicted drugs, eight of which did show activity against P. falciparum 3D7 clone. Seven had IC50 values ranging from 1 μM to 50 μM. This study also suggests drug-target association and hence possible mechanisms of action of drugs that did show antiplasmodial activity. The study results validate the use of proteome-wide target similarity approach in identifying approved drugs with activity against P. falciparum and could be adapted for other pathogens.

Background Change of direction (COD) movements are associated with non-contact anterior cruciate ligament (ACL) injuries in multidirectional sports. Females appear at increased risk compared to males, which could be attributable to whole body kinematic strategies and greater multiplanar knee joint loads (KJLs) during COD which can increase ACL loading. Objective The aim of this systematic review and meta-analysis was to examine and quantitatively synthesise the evidence for differences between males and females regarding KJLs and their biomechanical determinants (whole body kinematic strategies determining KJLs) during COD tasks. Methods Databases including SPORTDiscus, Web of Science, and PubMed were systematically searched (July 2021–June 2023) for studies that compared differences in knee joint loads and biomechanical determinants of KJLs during COD between males and females. Inclusion criteria were: (1) females and males with no prior history of ACL injury (18–40 years); (2) examined biomechanical determinants of KJLs and/ or KJLs during COD tasks > 20°; (3) compared ≥ 1 outcome measure between males and females. Studies published between 2000 and 2023 examining a cutting task > 20° with a preceding approach run that compared KJLs or the whole body multiplanar kinematics associated with them, between sexes, using three-dimensional motion analysis. Results This meta-analysis included 17 studies with a pooled sample size of 451 participants (227 males, 224 females). Meta-analysis revealed females displayed significantly less peak knee flexion during stance (SMD: 0.374, 95% CI 0.098–0.649, p  = 0.008, I 2 : 0%); greater knee abduction at initial contact (IC) (SMD: 0.687, 95% CI 0.299–1.076, p  = 0.001, I 2 : 55%); less hip internal rotation (SMD: 0.437, 95% CI 0.134–0.741, p  = 0.005, I 2 : 34%) and hip abduction at IC (SMD: −0.454, 95% CI 0.151–0.758, p  = 0.003, I 2 : 33%). No significant differences were observed between males and females for any internal or externally applied KJLs. All retrieved studies failed to control for strength, resistance training or skill history status. Conclusion No differences were observed in KJLs between males and females despite females displaying greater knee abduction at IC and less peak knee flexion during the stance phase of CODs, which are visual characteristics of non-contact ACL injury. Further research is required to examine if this translates to a similar injury risk, considering morphological differences in strain characteristics of the ACL between males and females. This observation may in part explain the disproportionate ACL injury incidence in female multidirectional athletes. Further higher quality controlled research is required whereby participants are matched by skill training history, resistance training history and strength status to ensure an appropriate comparison between males and females. Key Points No differences between sexes were found for multiplanar KJLs despite previous research supporting this. Further research is required to identify if this is the case and if it affects injury risk between males and females. Females displayed greater knee abduction at initial contact, less peak knee flexion during stance, and less hip rotation and abduction at IC together with less peak hip flexion during stance during CODs. Previous research has failed to account for confounding factors such as skill training history, resistance training history and strength status together with gendered environmental factors that could contribute to the misinterpretation of COD differences between males and females.

Background Cutting actions are associated with non-contact ACL injuries in multidirectional sports due to the propensity to generate large multiplanar knee joint loads (KJLs) that have the capacity to increase ACL loading and strain. Numerous studies have investigated the biomechanical determinants of KJLs in cutting tasks. The aim of this systematic review was to comprehensively review the literature regarding biomechanical determinants of KJLs during cutting, in order to develop a cutting technical framework alongside training recommendations for practitioners regarding KJL mitigation. Methods Databases (SPORTDiscus, Web of Science and PubMed) were systematically searched using a combination of the following terms: “Biomechanical determinants”, or “Knee abduction moment”, or “Technical determinants”, or “Knee loading”, or “Knee loads”, or “Mechanical determinants”, or “ACL strain”, or “Knee adduction moment”, or “Anterior tibial shear”, or “Knee internal rotation moment”, or “Knee valgus moment” AND “Change of direction”, or “Cutting manoeuvre”, or “Run and cut”, or “Run-and-cut”, or “Sidestepping”, or “Side-stepping”, or “Shuttle run”. Inclusion criteria were as follows: studies examining a cutting task < 110° with a preceding approach run that examined biomechanical determinants of KJLs using three-dimensional motion analysis. Results The search returned 6404 possibly eligible articles, and 6 identified through other sources. Following duplicate removal, 4421 titles and abstracts were screened, leaving 246 full texts to be screened for inclusion. Twenty-three full texts were deemed eligible for inclusion and identified numerous determinants of KJLs; 11 trunk, 11 hip, 7 knee, 3 multiplanar KJLs, 5 foot/ankle and 7 identifying ground reaction forces (GRFs) as determinants of KJLs. Conclusion Using the framework developed from the results, cutting KJLs can be mitigated through the following: reducing lateral foot-plant distances, thus lowering hip abduction and orientating the foot closer to neutral with a mid-foot or forefoot placement strategy; minimising knee valgus and hip internal rotation angles and motion at initial contact (IC) and weight acceptance (WA); avoiding and limiting lateral trunk flexion and attempt to maintain an upright trunk position or trunk lean into the intended direction; and finally, reducing GRF magnitude during WA, potentially by attenuation through increased knee flexion and emphasising a greater proportion of braking during the penultimate foot contact (PFC).

Antibiotic resistance poses a significant threat to human health, and wastewater treatment plants (WWTPs) are important reservoirs of antibiotic resistance genes (ARGs). Here, we analyze the antibiotic resistomes of 226 activated sludge samples from 142 WWTPs across six continents, using a consistent pipeline for sample collection, DNA sequencing and analysis. We find that ARGs are diverse and similarly abundant, with a core set of 20 ARGs present in all WWTPs. ARG composition differs across continents and is distinct from that of the human gut and the oceans. ARG composition strongly correlates with bacterial taxonomic composition, with Chloroflexi , Acidobacteria and Deltaproteobacteria being the major carriers. ARG abundance positively correlates with the presence of mobile genetic elements, and 57% of the 1112 recovered high-quality genomes possess putatively mobile ARGs. Resistome variations appear to be driven by a complex combination of stochastic processes and deterministic abiotic factors. Wastewater treatment plants are important reservoirs of antibiotic resistance genes (ARGs). Here, the authors analyze ARGs in a global collection of samples from wastewater treatment plants across six continents, providing insights into biotic and abiotic mechanisms that appear to control ARG diversity and distribution.

In recent large-scale cardiovascular outcome trials, two new classes of glucose-lowering medications—sodium glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs)—demonstrated cardiovascular benefits in adults with type 2 diabetes mellitus (T2DM). These findings have prompted growing optimism among clinicians regarding the potential for these agents to reduce the burden of cardiovascular disease in people with T2DM. GLP-1RAs and SGLT2i are now advocated as second-line agents in European and US guidelines for management of both hyperglycaemia and for primary prevention of cardiovascular disease in people with T2DM. Given the high prevalence of T2DM in patients with cardiovascular disease, cardiologists will increasingly encounter these agents in routine clinical practice. In this review, we summarise evidence from cardiovascular outcome trials of GLP-1RAs and SGLT2i, give practical advice on prescribing and detail safety considerations associated with their use. We also highlight areas where further work is needed, giving details on active clinical trials. The review aims to familiarise cardiologists with these emerging treatments, which will be increasingly encountered in clinical practice, given the expanding representation of T2DM in patients with cardiovascular disease. Whether these drugs will be initiated by cardiologists remains to be determined.

Two ombrotrophic bogs in Canada's Hudson Bay Lowlands (HBL), an area storing an estimated 33 Gt of soil carbon, are contrasted with the Mer Bleue temperate ombrotrophic bog approximately 1000 km to the southeast to assess the net carbon dioxide (CO2) exchange between these ecosystems and the atmosphere. Peatlands in the HBL region may be impacted by not only climate change but also resource extraction practices that may cause drying of surrounding areas. Two years of eddy covariance CO2 flux measurements show the two HBL bogs to be annual sinks for CO2. Given random error and gap-filling uncertainties of 6 to 13 g C m-2 yr-1, the annual budgets of 45 to 55 g C m-2 yr-1 for the HBL bogs did not differ significantly from the temperate bog's budget of 55 g C m-2 yr-1 (in the first year) despite differences in climate and vegetation composition and abundance. The temperate bog did have significantly greater net uptake of CO2 (78 g C m-2 yr-1) in the second study year. Component fluxes of photosynthesis and respiration were much smaller at the HBL bogs and speculated to be a result of less vascular vegetation. Less growing season CO2 uptake at the HBL bogs was offset by less winter loss when compared to the temperate bog. The influence of mid-summer drying and lowered water tables was similar among all three bogs. Decreasing mid-summer net ecosystem productivity (NEP) appeared to be a result of reduced photosynthetic uptake rather than increased respiration. In the short-term, drying of the HBL peatlands might result in a decrease of their C sink strength.

Background: Schools are high-risk settings for infectious disease transmission. Wastewater monitoring for infectious diseases has been used to identify and mitigate outbreaks in many near-source settings during the COVID-19 pandemic, including universities and hospitals but less is known about the technology when applied for school health protection. This study aimed to implement a wastewater surveillance system to detect SARS-CoV-2 and other public health markers from wastewater in schools in England. Methods: A total of 855 wastewater samples were collected from 16 schools (10 primary, 5 secondary and 1 post-16 and further education) over 10 months of school term time. Wastewater was analysed for SARS-CoV-2 genomic copies of N1 and E genes by RT-qPCR. A subset of wastewater samples was sent for genomic sequencing, enabling determination of the presence of SARS-CoV-2 and emergence of variant(s) contributing to COVID-19 infections within schools. In total, >280 microbial pathogens and >1200 AMR genes were screened using RT-qPCR and metagenomics to consider the utility of these additional targets to further inform on health threats within the schools. Results: We report on wastewater-based surveillance for COVID-19 within English primary, secondary and further education schools over a full academic year (October 2020 to July 2021). The highest positivity rate (80.4%) was observed in the week commencing 30th November 2020 during the emergence of the Alpha variant, indicating most schools contained people who were shedding the virus. There was high SARS-CoV-2 amplicon concentration (up to 9.2x106 GC/L) detected over the summer term (8th June - 6th July 2021) during Delta variant prevalence. The summer increase of SARS-CoV-2 in school wastewater was reflected in age-specific clinical COVID-19 cases. Alpha variant and Delta variant were identified in the wastewater by sequencing of samples collected from December to March and June to July, respectively. Lead/lag analysis between SARS-CoV-2 concentrations in school and WWTP data sets show a maximum correlation between the two-time series when school data are lagged by two weeks. Furthermore, wastewater sample enrichment coupled with metagenomic sequencing and rapid informatics enabled the detection of other clinically relevant viral and bacterial pathogens and AMR. Conclusions: Passive wastewater monitoring surveillance in schools can identify cases of COVID-19. Samples can be sequenced to monitor for emerging and current variants of concern at the resolution of school catchments. Wastewater based monitoring for SARS-CoV-2 is a useful tool for SARS-CoV-2 passive surveillance and could be applied for case identification and containment, and mitigation in schools and other congregate settings with high risks of transmission. Wastewater monitoring enables public health authorities to develop targeted prevention and education programmes for hygiene measures within undertested communities across a broad range of use cases.