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Abstract Background Ticks are obligate hematophagous ectoparasites involved in transmitting viruses of public health importance. The objective of this work was to identify the Jingmen tick virus in hard ticks from the Colombian Caribbean, an arbovirus of importance for public health. Methods Ticks were collected in rural areas of Córdoba and Cesar, Colombia. Taxonomic identification of ticks was carried out, and pools of 13 individuals were formed. RNA extraction was performed. Library preparation was performed with the MGIEasy kit, and next-generation sequencing (NGS) with MGI equipment. Bioinformatic analyses and taxonomic assignments were performed using the Galaxy platform, and phylogenetic analyses were done using IQ-TREE2. Results A total of 766 ticks were collected, of which 87.33% (669/766) were Rhipicephalus microplus, 5.4% (42/766) Dermacentor nitens, 4.2% (32/766) Rhipicephalus linnaei, and 3.0% (23/766) Amblyomma dissimile. Complete and partial segments 1, 2, 3, and 4 of Jingmen tick virus (JMTV) were detected in the metatranscriptome of the species R. microplus, D. nitens, and A. dissimile. The JMTVs detected are phylogenetically related to JMTVs detected in Aedes albopictus in France, JMTVs detected in R. microplus in Trinidad and Tobago, JMTVs in R. microplus and A. variegatum in the French Antilles, and JMTVs detected in R. microplus in Colombia. Interestingly, our sequences clustered closely with JMTV detected in humans from Kosovo. Conclusions JMTV was detected in R. microplus, D. nitens, and A. dissimile. JMTV could pose a risk to humans. Therefore, it is vital to establish epidemiological surveillance measures to better understand the possible role of JMTV in tropical diseases. Graphical Abstract

Abstract Background The study of parasites provides insight into intricate ecological relationships in ecosystem dynamics, food web structures, and evolution on multiple scales. Hepatozoon (Eucoccidiorida: Hepatozoidae) is a genus of protozoan hemoparasites with heteroxenous life cycles that switch infections between vertebrates and blood-feeding invertebrates. The most comprehensive review of the genus was published 26 years ago, and currently there are no harmonized data on the epizootiology, diagnostics, genotyping methods, evolutionary relationships, and genetic diversity of Hepatozoon in the Americas. Methods Here, we provide a comprehensive review based on the PRISMA method regarding Hepatozoon in wild mammals within the American continent, in order to generate a framework for future research. Results 11 out of the 35 countries of the Americas (31.4%) had data on Hepatozoon, with Carnivora and Rodentia orders having the most characterizations. Bats, ungulates, and shrews were the least affected groups. While Hepatozoon americanum, H. americanum-like, H. canis, H. didelphydis, H. felis, H. milleri, H. griseisciuri, and H. procyonis correspond to the identified species, a plethora of genospecies is pending for a formal description combining morphology and genetics. Most of the vectors of Hepatozoon in the Americas are unknown, but some flea, mite, and tick species have been confirmed. The detection of Hepatozoon has relied mostly on conventional polymerase chain reaction (PCR), and the implementation of specific real time PCR for the genus needs to be employed to improve its diagnosis in wild animals in the future. From a genetic perspective, the V4 region of the 18S rRNA gene has been widely sequenced for the identification of Hepatozoon in wild animals. However, mitochondrial and apicoplast markers should also be targeted to truly determine different species in the genus. A phylogenetic analysis of herein retrieved 18S ribosomal DNA (rDNA) sequences showed two main clades of Hepatozoon: Clade I associated with small mammals, birds, and herpetozoa, and Clade II associated with Carnivora. The topology of the tree is also reflected in the haplotype network. Conclusions Finally, our review emphasizes Hepatozoon as a potential disease agent in threatened wild mammals and the role of wild canids as spreaders of Hepatozoon infections in the Americas. Graphical Abstract

Objectives Long-term sickness absence from employment has negative consequences for the economy and can lead to widened health inequalities. Sick notes (also called ‘fit notes’) are issued by general practitioners when a person cannot work for health reasons for more than 7 days. We quantified the sick note rate in people with evidence of COVID-19 in 2020, 2021 and 2022, as an indication of the burden for people recovering from COVID-19.Design Cohort study.Setting With National Health Service (NHS) England approval, we used routine clinical data (primary care, hospital and COVID-19 testing records) within the OpenSAFELY-TPP database.Participants People 18–64 years with a recorded positive test or diagnosis of COVID-19 in 2020 (n=365 421), 2021 (n=1 206 555) or 2022 (n=1 321 313); general population matched in age, sex and region in 2019 (n=3 140 326), 2020 (n=3 439 534), 2021 (n=4 571 469) and 2022 (n=4 818 870); people hospitalised with pneumonia in 2019 (n=29 673).Primary outcome measure Receipt of a sick note in primary care.Results Among people with a positive SARS-CoV-2 test or COVID-19 diagnosis, the sick note rate was 4.88 per 100 person-months (95% CI 4.83 to 4.93) in 2020, 2.66 (95% CI 2.64 to 2.67) in 2021 and 1.73 (95% CI 1.72 to 1.73) in 2022. Compared with the age, sex and region-matched general population, the adjusted HR for receipt of a sick note over the entire follow-up period (up to 10 months) was 4.07 (95% CI 4.02 to 4.12) in 2020 decreasing to 1.57 (95% CI 1.56 to 1.58) in 2022. The HR was highest in the first 30 days postdiagnosis in all years. Among people hospitalised with COVID-19, after adjustment, the sick note rate was lower than in people hospitalised with pneumonia.Conclusions Given the under-recording of postacute COVID-19-related symptoms, these findings contribute a valuable perspective on the long-term effects of COVID-19. Despite likely underestimation of the sick note rate, sick notes were issued more frequently to people with COVID-19 compared with those without, even in an era when most people are vaccinated. Most sick notes occurred in the first 30 days postdiagnosis, but the increased risk several months postdiagnosis may provide further evidence of the long-term impact.

BackgroundObservational studies have described associations of maternal smoking during pregnancy with intellectual disability (ID) in the exposed offspring. Whether these results reflect a causal effect or unmeasured confounding is still unclear.MethodsUsing a UK-based prospectively collected birth cohort (the Avon Longitudinal Study of Parents and Children) of 13,479 children born between 1991 and 1992, we assessed the relationship between maternal smoking at 18 weeks’ gestation and offspring risk of ID, ascertained through multiple sources of linked information including primary care diagnoses and education records. Using confounder-adjusted logistic regression, we performed observational analyses and a negative control analysis that compared maternal with partner smoking in pregnancy under the assumption that if a causal effect were to exist, maternal effect estimates would be of greater magnitude than estimates for partner smoking if the two exposures suffer from comparable biases.ResultsIn observational analysis, we found an adjusted odds ratio for ID of 0.75 (95% CI = 0.49–1.13) for any maternal smoking and 0.97 (95% CI = 0.71–1.33) per 10-cigarette increase in number of cigarettes smoked per day. In negative control analysis, comparable effect estimates were found for any partner smoking (OR = 0.94; 95% CI = 0.63–1.40) and number of cigarettes smoked per day (OR = 0.94; 95% CI = 0.74–1.20).ConclusionsThe results are not consistent with a causal effect of maternal smoking during pregnancy on offspring ID.

Tick-borne infectious agents (TBIAs) include several bacteria and protozoa that can infect vertebrates, including humans. Some of these agents can cause important diseases from both a public health perspective, such as Lyme disease, and from an animal health and production viewpoint, such as Texas fever. In Chile, several studies have assessed the presence of tick-borne disease agents in vectors and mammal hosts, mainly in the northern regions, but few studies have assessed the presence of these agents in Central and Southern Chile. This study aimed to assess the presence of three groups of TBIAs—Borrelia, Anaplasmataceae, and Piroplasmida—in cricetid rodents of Central and Southern Chile. A total of 207 specimens from 13 localities between the O’Higgins and Los Lagos regions were captured. DNA was extracted from the liver and spleen, and subsequently underwent polymerase chain reaction (PCR) amplification targeting the 16S rRNA, flaB, and 18S rRNA genes to detect DNA from Borrelia, Anaplasmataceae, and Piroplasmida, respectively. Although no DNA from these TBIAs was detected, the DNA extraction process was validated by optimal DNA purity ratios (an A260/A280 ratio within the 1.6–2.0 range) and successful internal control amplification in all samples. These results, in addition to findings from previous reports, suggest a very low prevalence of these TBIAs in the rodent population studied. Further research into the factors influencing the presence of these agents and their vectors will provide insight into the reasons underlying this low prevalence.

The Amblyomma marmoreum complex includes afrotropical species, such as Amblyomma sparsum, a three-host tick that parasitizes reptiles, birds, and mammals, and is a recognized vector of Ehrlichia ruminantium. However, the lack of morphological, genetic and ecological data on A. sparsum has caused considerable confusion in its identification. In this study, we used microscopy and metagenomic approaches to analyze A. sparsum ticks collected from a puff adder snake (Bitis arietans) in southwest Senegal (an endemic rickettsioses area) in order to supplement previous morphological descriptions, provide novel genomic data for the A. marmoreum complex, and describe the genome of a novel spotted fever group Rickettsia strain. Based on stereoscope and scanning electron microscopy (SEM) morphological evaluations, we provide high-quality images and new insights about punctation and enameling in the adult male of A. sparsum to facilitate identification for future studies. The metagenomic approach allowed us assembly the complete mitochondrial genome of A. sparsum, as well as the nearly entire chromosome and complete plasmid sequences of a novel Rickettsia africae strain. Phylogenomic analyses demonstrated a close relationship between A. sparsum and Amblyomma nuttalli for the first time and confirmed the position of A. sparsum within the A. marmoreum complex. Our results provide new insights into the systematics of A. sparsum and A. marmoreum complex, as well as the genetic diversity of R. africae in the Afrotropical region. Future studies should consider the possibility that A. sparsum may be a vector for R. africae.

Background: Increasing evidence suggests that air pollution exposure contributes to the development of mental health problems, including psychosis and depression. However, little is known about the importance of early-life exposure, nor the potential role of noise pollution, a correlate of air pollution. We examined the association of exposure to air and noise pollution from pregnancy to age 12 years with three mental health problems assessed at ages 12, 18, and 24 years. Methods: Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC), which tracks the development of about 14 000 babies who had expected delivery dates between April 1, 1991, and Dec 31, 1992, in Avon, UK. This was linked with novel data on nitrogen dioxide, PM2·5, and noise pollution in pregnancy, childhood (ages 1–9 years), and adolescence (ages 10–12 years). Psychotic experiences, depression, and anxiety were measured at ages 12, 18, and 24 years. Logistic regression models were controlled for individual-level, family-level, and area-level confounders, and e-values were calculated to estimate residual confounding. Findings: Participants exposed to higher PM2.5, particularly during pregnancy, had greater odds for psychotic experiences (adjusted odds ratio 1·17 [95% CI 1·05–1·30]) and depression (1·11 [1·01–1·22]). There was little evidence associating nitrogen dioxide or noise pollution with psychotic experiences or depression. Conversely, higher nitrogen dioxide (but not PM2·5) exposure in pregnancy (1·16 [1·01–1·33]), and higher noise pollution in childhood (1·20 [1·06-1·37]) and adolescence (1·17 [1·02-1·35]), were associated with greater odds for anxiety. Interpretation: Our study builds on evidence linking air pollution to psychosis and depression and provides rare longitudinal evidence linking noise pollution to anxiety. Our findings indicate that air pollution exposure earlier in development (eg, during pregnancy) might be particularly important, and suggest a degree of specificity in terms of pollutant-outcome associations. If causal, our findings suggest that interventions to reduce air pollution would improve global mental health. Funding: Wellcome Trust, UK Medical Research Council–Wellcome, and University of Bristol.

The construction industry is recognized for its high consumption of natural resources, resulting in significant environmental impacts. Given this reality, it is essential to seek new methods and solutions that minimize the impact of this activity on the environment. An innovative approach consists of using pigments derived from acid mine drainage (AMD) as a sustainable alternative in the production of mortar for decorative façade cladding. In this context, the main objective of this paper was to evaluate the physical/mechanical properties of decorative mortars developed by partially replacing natural sand with pigment from acid mine drainage. Initially, the pigment (yellow) was produced, characterized, and compared with a commercial pigment. Sequentially, decorative mortars were developed with different pigment concentrations (0%, 2%, 4%, and 6%). The mortars were subjected to compressive strength, flexural tensile strength, shrinkage, loss of mass, and colorimetry tests. The results showed that compressive strength, flexural tensile strength, weight loss, and dimensional variation were significantly affected by the partial addition of pigment to replace natural aggregate. In other words, there was a decrease in strength and an increase in mass loss and expansion of the mortars. However, the main factor influencing these variables was the greater amount of water added in the higher substitution cases. The addition of water was necessary to keep the consistency constant. A possible solution to maintain the same amount of water and avoid negative effects on the mortar properties would be to use additives in the mortar formulation in future work. Therefore, this research contributes to the search for more sustainable solutions in civil construction, exploring the use of pigments from AMD as a viable alternative to reduce the environmental impacts associated with this industry.

IntroductionCardiac magnetic resonance (CMR) is of diagnostic and prognostic value in a range of cardiopulmonary conditions. Current methods for evaluating CMR studies are laborious and time-consuming, contributing to delays for patients. As the demand for CMR increases, there is a growing need to automate this process. The application of artificial intelligence (AI) to CMR is promising, but the evaluation of these tools in clinical practice has been limited. This study assessed the clinical viability of an automatic tool for measuring cardiac volumes on CMR.MethodsConsecutive patients who underwent CMR for any indication between January 2022 and October 2022 at a single tertiary centre were included prospectively. For each case, short-axis CMR images were segmented by the AI tool and manually to yield volume, mass and ejection fraction measurements for both ventricles. Automated and manual measurements were compared for agreement and the quality of the automated contours was assessed visually by cardiac radiologists.Results462 CMR studies were included. No statistically significant difference was demonstrated between any automated and manual measurements (p > 0.05; independent T-test). Intraclass correlation coefficient and Bland-Altman analysis showed excellent agreement across all metrics (ICC > 0.85). The automated contours were evaluated visually in 251 cases, with agreement or minor disagreement in 229 cases (91.2%) and failed segmentation in only a single case (0.4%). The AI tool was able to provide automated contours in under 90 s.ConclusionsAutomated segmentation of both ventricles on CMR by an automatic tool shows excellent agreement with manual segmentation performed by CMR experts in a retrospective real-world clinical cohort. Implementation of the tool could improve the efficiency of CMR reporting and reduce delays between imaging and diagnosis.

Babesia spp. are tick-borne protozoans that involve birds and mammals in their transmission cycles and cause babesiosis, a severe hemolytic malaria-like disease. Opossums of the genus Didelphis are recognized hosts of tick-borne pathogens. Therefore, exploring tick-borne agents in Didelphis species is important to understand the circulation of pathogens in areas where opossums occur. In this study, we targeted Anaplasmataceae, Babesia, Borrelia and Hepatozoon DNA in ticks, blood and organ samples collected from three hunted Didelphis marsupialis specimens in eastern Guatemala. While the samples were negative for Hepatozoon and bacterial DNA, sequences of Babesia 18S rDNA, cox1 and cytb genes were retrieved from two opossums. Ticks collected on the animals included Amblyomma parvum and an undetermined Ornithodoros sp. The Babesia sp. detected in this study (Babesia sp. THB1–2) clusters phylogenetically within the “Western Babesia group”, which includes pathogenic species such as Babesia conradae, Babesia duncani, and Babesia negevi. Our results represent the first record of a Babesia sp. in Guatemala and highlight the importance of D. marsupialis as potential spreaders of ticks and pathogens in Central America.

Introduction: Accurately diagnosing asthma can be challenging. We aimed to derive and validate a prediction model to support primary care clinicians assess the probability of an asthma diagnosis in children and young people. Methods: The derivation dataset was created from the Avon Longitudinal Study of Parents and Children (ALSPAC) linked to electronic health records. Participants with at least three inhaled corticosteroid prescriptions in 12-months and a coded asthma diagnosis were designated as having asthma. Demographics, symptoms, past medical/family history, exposures, investigations, and prescriptions were considered as candidate predictors. Potential candidate predictors were included if data were available in ≥60% of participants. Multiple imputation was used to handle remaining missing data. The prediction model was derived using logistic regression. Internal validation was completed using bootstrap re-sampling. External validation was conducted using health records from the Optimum Patient Care Research Database (OPCRD). Results: Predictors included in the final model were wheeze, cough, breathlessness, hay-fever, eczema, food allergy, social class, maternal asthma, childhood exposure to cigarette smoke, prescription of a short acting beta agonist and the past recording of lung function/reversibility testing. In the derivation dataset, which comprised 11,972 participants aged

Objectives Our Trusted Research Environment (TRE) provides a centralised infrastructure to pool Longitudinal Population Studies’ (LPS) data and systematically link participants’ routine health, administrative and environmental records. All data are held in a centralised research resource which is now certified by UK Statistics Authority as meeting the Digital Economy Act standard. Approach We have created an unprecedented infrastructure integrating data from interdisciplinary and pan-UK LPS linked to participants’ NHS England records with delegated access responsibilities. Integrated and curated data are made available for pooled analysis within a functionally anonymous DEA and ISO 27001 accredited TRE. We developed a bespoke governance and data curation framework with LPS data managers and Public/participant contributors. New data pipelines are being built with partners at ADRUK and the Office of National Statistics to link non-health records. Our design supports long-term sustainability, linkage accuracy and the ability to link data at both an individual and household level. Results This organisation is a collaboration of >24 LPS with ~280,000 participants. Participants' data are linked to NHS records and geo-coded environmental exposures. This resource is now accessible for public benefit research for bona fide UK researchers. Administrative data including tax, work and pensions, and education are being added to the resource. This data flow is enabled by: (1) a model where TTP processes participant identifiers for many different data owners; (2) creation of a novel longitudinal data pipeline, enabling linkage, data extraction and update of records over time; (3) an access framework where Linked Data Access Panel considers applications on behalf of data owners (e.g., the NHS), with review by a Public Panel and distributing applications to LPS for approval of appropriate data use. Conclusion Our organisation provides a strategic research-ready platform for longitudinal research. We are extending linkages of LPS participants to previously inaccessible datasets. The research resource is positioned to allow researchers to investigate cross-cutting themes such as understanding health and social inequalities, health-social-environmental interactions, and managing the COVID-19 recovery.

Objectives We created a panel with members of the public and longitudinal study participants who review our data access requests. This panel forms an integral part of our data access application process, giving the public a say who can access the data for research. Methods We advertised our lay member vacancies using social media, newsletters, word of mouth and the internet. We appointed six people to the public panel. Our panel includes study participants, NHS service users, parents, carers, and people with experience of disability, neurodiversity, and long-term health conditions. The Panel Terms of Reference were created with help from stakeholders and study teams involved in longitudinal studies that involve the public in data access applications. This ensured that the purpose of the panel was clear. The panel reviews lay summaries and makes sure that researchers have adequate public involvement in their project. Results Panel members have reviewed 28 applications. Researchers present their research at an online meeting with the panel then answer questions from the panel members. We publish meeting minutes on our website for transparency. A 6-month review was overwhelmingly positive - all panel members indicated they felt valued. They felt able to challenge and question researchers as part of the data access application process. This provides a level of public scrutiny to our work. “I feel there’s a real value in the panel. You get a real sense that this has got such potential to make a contribution.” (panel member) We are further developing the Panel Terms of Reference with panel members. We will consider additional areas of responsibility, for example, public benefit review. Conclusion We regularly review how to improve public involvement in our work. The panel has proven its value during our application process. Therefore we are exploring with the panel a new approach to assess the public benefit of applications and what is meant by ‘public benefit research’.

Abstract Background Deer species play an important role in the enzootic cycles of several Anaplasma species. While in the Northern Hemisphere ticks of genus Ixodes are well recognized vectors of these intracellular bacteria, less is known regarding the biological cycles of Anaplasma spp. in South America. Methods Using PCR protocols and Sanger sequencing, we assessed the presence of Anaplasma spp. in blood and ticks collected on a native deer species (Pudu puda) from southern Chile. Results Based on phylogenetic analyses of the 16S rRNA, gltA and groEL genes and calculation of average sequence divergence for groEL, our results bring to light a novel genovariant of Anaplasma phagocytophilum (named strain “Patagonia”). The strain represents a novel ecotype within the A. phagocytophilum species complex and was detected in both P. puda and their ticks. Using a larger matrix, denser taxon sampling and outgroup, our maximum-likelihood- and Bayesian-inferred phylogenies for groEL provide an accurate picture of the topology of A. phagocytophilum ecotypes and their evolutionary relationships. Conclusions This is the first report of an ecotype of A. phagocytophilum in South America. Our results provide novel insight into the genetic diversity and ecology of this complex of bacterial lineages. Further studies should elucidate the enzootic cycle of A. phagocytophilum strain “Patagonia” and assess its pathogenic potential for pudues, domestic animals and humans in the region. Graphical Abstract

Abstract Background In partnership with a Nehiyawak (Plains Cree) community of Maskwacîs,central Alberta (Canada), we implemented an Indigenous-led intervention to provide experiential learning opportunities for perinatal health care providers (HCPs) and staff. Our objective was to capture the impact of participating in cultural safety learning opportunities on perceived self-awareness for HCPs and staff to provide enhanced culturally informed care. Methods Perinatal HCPs and staff who work regularly with Indigenous women from our partnering community took part in a series of experiential learning activities designed by a Community Advisory Committee. We used an explanatory sequential mixed methods approach informed by community-based participatory research. We compared Cultural Intelligence Scale (CQS) and Maskwacîs-Specific Cultural Scale (MSCS) scores pre- and post-intervention using non-parametrical statistical analysis (Wilcoxon signed rank test). Post-intervention, we conducted a qualitative description study using semi-structured interviews. Qualitative data was analyzed using thematic analysis. Results A total of 17 participants completed pre- and post-intervention questionnaires. Responses indicated a shift in perceived cultural and community knowledge and comfort levels, with positive gains in overall mean scores for both the CQS (p = 0.01) and MSCS (p = 0.01). Nine participants completed qualitative interviews. Overall, participants felt better equipped to provide more culturally informed care to their patients post-intervention. Conclusion An Indigenous-led experiential learning intervention was effective in enhancing overall perceived cultural awareness and preparedness to provide culturally informed care for perinatal HCPs and staff. This study provides evidence for fostering relationships between Indigenous communities and health systems toward enhanced perinatal care.

Abstract Objectives There is growing evidence that excess adipose tissue within the head and neck contributes to obstructive sleep apnea (OSA), particularly in obese patients. This subset of the population is often difficult to treat with surgical therapies. We theorized that a novel, transcervical method of injectable cryoablation using ice‐slurry can achieve low temperatures without causing neurovascular damage or airway distress in a swine model. Methods Four Yorkshire pigs were injected with ice‐slurry comprised of normal saline and 10% glycerol cooled to −6°C via a transcervical, ultrasound guided approach. Direct laryngoscopy was used to confirm accurate placement of the slurry. Thermocouple placement at the needle‐tip was used to measure temperatures at injection site. Swine were monitored for clinical signs of tongue necrosis and airway edema for 2 months, and then euthanized. Twelve biopsy samples from the base of the tongue were collected for histology. These were assessed for presence of tissue damage, inflammation and collagen formation by a blinded board‐certified pathologist. Results Tongue tissue temperature below 10°C was achieved for 13.5 ± 1.1 min. Minimum tissue temperature was −4 ± 0.6°C. There was no clinical or pathological evidence of tongue damage to include damage to the lingual nerve or artery. There was some histologic evidence of new collagen formation in areas of the tongue. Conclusions Transcervical ultrasound‐guided ice‐slurry injection is feasible, well‐tolerated at temperatures previously shown to be capable of selectively targeting adipose tissue in the base of the tongue in a preclinical swine model, without causing neurovascular damage or airway distress when properly injected.

Summary: Background: The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. Methods: In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23, 2020. Findings: Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences. Interpretation: Our study suggests that ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes. Funding: LSHTM COVID-19 Response Grant (DONAT15912).

The FeedSax project combined bioarchaeological data with evidence from settlement archaeology to investigate how, when and why the expansion of arable farming occurred between the 8th-13th centuries in England. It has generated and released a vast, multi-faceted archaeological dataset both to underpin its own published findings and to support further research.

This data note describes a new resource for crime-related research: the Avon Longitudinal Study of Parents and Children (ALSPAC) linked to regional police records. The police data were provided by Avon & Somerset Police (A&SP), whose area of responsibility contains the ALSPAC recruitment area. In total, ALSPAC had permission to link to crime records for 12,662 of the ‘study children’ (now adults, who were born in the early 1990s). The linkage took place in two stages: Stage 1 involved the ALSPAC Data Linkage Team establishing the linkage using personal identifiers common to both the ALSPAC participant database and A&SP records using deterministic and probabilistic methods. Stage 2 involved A&SP extracting attribute data on the matched individuals, removing personal identifiers and securely sharing the de-identified records with ALSPAC. The police data extraction took place in July 2021, when the participants were in their late 20s/early 30s. This data note contains details on the resulting linked police records available. In brief, electronic police records were available from 2007 onwards. In total, 1757 participants (14%) linked to at least one police record for a charge, offence ‘taken into consideration’, caution, or another out of court disposal. Linked participants had a total of 6413 records relating to 6283 offences. Almost three quarters of the linked participants were male. The most common offence types were violence against the person (22% of records), drug offences (19%), theft (17%) and public order offences (11%). This data note also details important issues that researchers using the local police data should be aware of, including the importance of defining an appropriate denominator, completeness, and biases affecting police records.

Background: Intellectual disability (ID) describes a neurodevelopmental condition involving impaired cognitive and functional ability. Here, we describe a multisource variable of ID using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Methods: The multisource indicator variable for ID was derived from i) IQ scores less than 70 measured at age 8 and at age 15, ii) free text fields from parent reported questionnaires, iii) school reported provision of educational services for individuals with a statement of special educational needs for cognitive impairments, iv) from relevant READ codes contained in GP records, iv) international classification of disease diagnoses contained in electronic hospital records and hospital episode statistics and v) recorded interactions with mental health services for ID contained within the mental health services data set. A case of ID was identified if two or more sources indicated ID. A second indicator, labelled as “probable ID”, was created by relaxing the cut off in IQ scores to be less than 85. An indicator variable for known causes of ID was also created to aid in aetiological studies where ID with a known cause may need to be excluded. Results: 158 of 14,370 participants (1.10%) were indicated as having ID by two or more sources and 449 (3.12%) were indicated as having probable ID when the criteria for IQ scores was relaxed to less than 85. There were 476 participants (3.31%) with 1 or fewer sources of available information on ID; these participants had their multisource variable set to missing. The number of cases of ID with known cause was 31 (0.22% of the cohort, 19.6% of those with ID). Conclusions: The multisource variable of ID can be used in future analyses on ID in ALSPAC children.

Introduction: Linking longitudinal cohort resources with police-recorded records of criminal activity has the potential to inform public health style approaches to policing, and may reduce potential sources of bias from self-reported criminal data collected by cohort studies. A pilot linkage of police records to the Avon Longitudinal Study of Parents and Children (ALSPAC) allows us to consider the acceptability of this linkage, its utility as a data resource, differences in self-reported crime according to consent status for data linkage, and the appropriate governance mechanism to support such a linkage. Methods: We carried out a pilot study linking data from the ALSPAC birth cohort to Ministry of Justice (MoJ) records on criminal cautions and convictions. This pilot was conducted on a fully anonymous basis, meaning we cannot link the identified records to any participant or the wider information within the dataset. Using ALSPAC data, we used summary statistics to investigate differences in socio-economic background and self-reported criminal activity by consent status for crime linkage. We used MoJ records to identify the geographic and temporal concentration of criminality in the ALSPAC cohort. Results: We found that the linkage appears acceptable to participants (4% of the sample opted out), levels of criminal caution and conviction are high enough to support research, and that the majority of crimes occurred in Avon & Somerset (the policing area local to ALSPAC). Those who did not respond to consent requests had higher levels of self-reported criminal behaviour compared to participants who provided explicit consent. Conclusions: These findings suggest that data linkage in ALSPAC provides opportunities to study criminal behaviour and that linked individual-level records could provide robust research in the area. Our findings also suggest the potential for bias when only including participants who have explicitly consented to data linkage, highlighting the limitations of opt-in consent strategies.

Objectives The UK Longitudinal Linkage Collaboration (UKLLC) was established to link and integrate data from many longitudinal population studies (LPS) with participants’ records from diverse governmental data owners across the UK. The UKLLC aims to unify disparate requirements from many data owners in different legal jurisdictions into one, predictable, access framework. Approach The UKLLC framework provides a legal and governance ‘funnel’ which enables diverse data owner requirements to be captured; for UKLLC to centrally control these; and - from a research applicants perspective - there to be a predictable single process that is bound into emerging national standards for data science (e.g., the ‘Five Safes’ framework). This is applied through a Trusted Research Environment (TRE) approach where ISO27001 and Digital Economy Act accredited contracts, data sharing agreements, policies and procedures define and permit data flows and provide organisational separation of key functions including the third-party processing of participant identifiers for linkages. Results We developed a project review mechanism enabling UKLLC to efficiently process applications whilst respecting core data owners requirements: each aspect of this is tailored to relevant legal, jurisdictional and accreditation requirements. Contracting specialist processors enabled UKLLC to implement ‘organisational separation’ between use of participant identifiers and de-personalised data, enabling a ‘functionally anonymous’ approach facilitating efficient onward sharing of integrating data. The processes we have developed promote transparency and trust with regulators, participants and public. UKLLC host (University of Bristol) is able to be the data controller of data within the UKLLC; make application decisions; create the Licenced Dataset; and, curate and reuse data and metadata products of the research whilst data is maintained functionally anonymous. Large-scale complex linked data-sets are provisioned in a timely manner. Conclusion The UKLLC is part of a large ecosystem of organisations. A delegated and distributed model has been established supported by our contracts and policy. This configuration has allowed the delivery of cross-cutting data-sets to address priority Covid-19 research questions and a generalisable and sustainable model for the future

Objectives The COVID-19 Longitudinal Health and Wellbeing National Core Study utilises data from Longitudinal Population Studies (LPS) and whole-population NHS databases: yet no resource existed linking multiple LPS to COVID-19 records. A centralised infrastructure was needed to pool LPS data and systematically link participants’ routine health, administrative and environmental records. Approach The UK Longitudinal Linkage Collaboration (UK LLC) is an unprecedented infrastructure integrating data from major inter-disciplinary and pan-UK LPS and systematically linking these to participants’ COVID-19 relevant records. Integrated and curated data are made available for pooled analysis within a functionally anonymous Trusted Research Environment (TRE). We commissioned a “Secure eResearch Platform - SeRP” to provide an underlying secure computing system including trusted third-party processing of participant identifiers. We developed a bespoke governance and data curation framework designed collaboratively with LPS data managers and with an access mechanism enabling LPS to retain key decision-making controls. Public/participant involvement guided our approach. Results Data from >20 LPS and >250,000 Participants' are linked to NHS records (primary, secondary, community care; COVID-19; civic registers; prescriptions; mental health) and geo-coded environmental exposures (pollution, green space, neighbourhood indicators). UKLLC is now accessible to UK-wide researchers for COVID-19 research. Our pipeline/resource/provision of linked data is based on three key innovations: (1) a “Linkage brokerage” model where our trusted third-party processes participant identifiers for many different data owners; (2) a novel longitudinal data pipeline with NHS records which enables linkage and data extraction and update of records over time; (3) a “Delegated & Distributed Access Framework” enabling UK LLC Data Access Panel to consider applications on behalf of data owners (e.g., the NHS) whilst distributing applications to LPS for approval of appropriate data use. Conclusion UK LLC provides a strategic research-ready platform for longitudinal research: a clear step change from pre-pandemic capability. With sustained investment, and through exploring options to extend linkages and generalise to wider purposes, UK LLC is positioned to inform cross-cutting themes such as understanding health and social inequalities, health-social-environmental interactions, and managing the COVID-19 recovery.

Objectives The UK Longitudinal Linkage Collaboration (UK LLC) is a new, unprecedented infrastructure enabling research into the COVID-19 pandemic. The UK LLC integrates data from >20 UK longitudinal studies with systematically linked health, administrative and environmental records to facilitate cross-disciplinary COVID-19 research for accredited UK based researchers. Approach Bringing together all of the key components that form the UK LLC was a huge challenge that may have only been possible in the midst of the pandemic. First, we collaborated with the Longitudinal Population Studies (LPS) to create and agree how data linkage, data provision and applications to access the UK LLC would work. In parallel, public contributors helped to create fair processing materials. Finally, we worked closely with NHS Digital and other key national data providers to organise approvals for all studies to be linked, and for the UK LLC to have delegated decision-making for research applications. Results We faced a myriad of challenges creating the UK LLC including: • Short timeframe and short-term funding structure – initial funding for six months with an 18-month extension. • Working across >20 different LPS and four nations with different structures for access, consent and data provision. • Lack of capacity at various points in the data pipeline due to the volume of COVID-19 research required and underway across the involved organisations. • Data processing complexities – split data method means no one can see the entire process therefore catching linkage errors requires working across four different organisations. • With such complex data flows it is challenging to find the balance with communications about data to the public – being accurate about what we are doing, but expressing the complexity in lay terms. Conclusion Creating the UK LLC required collaboration with LPS, data providers and researchers. An iterative approach to creating the data application and data provision pipelines was crucial in developing these processes. The UK LLC was built quickly, from initial funding in October 2020 to provisioning data to researchers in December 2021.

India has the largest area of rainfed dryland agriculture globally, with a variety of distinct types of farming systems producing most of its coarse cereals, food legumes, minor millets, and large amounts of livestock. All these are vital for national and regional food and nutritional security. Yet, the rainfed drylands have been relatively neglected in mainstream agricultural and rural development policy. As a result, significant social-ecological challenges overlap in these landscapes: endemic poverty, malnutrition and land degradation. Sustainable intensification of dryland agriculture is essential for helping to address these challenges, particularly in the context of accelerating climate change. In this paper, we present 100 questions that point to the most important knowledge gaps and research priorities. If addressed, these would facilitate and inform sustainable intensification in Indian rainfed drylands, leading to improved agricultural production and enhanced ecosystem services. The horizon scanning method used to produce these questions brought together experts and practitioners involved in a broad range of disciplines and sectors. This exercise resulted in a consolidated set of questions covering the agricultural drylands, organized into 13 themes. Together, these represent a collective programme for new cross- and multi-disciplinary research on sustainable intensification in the Indian rainfed drylands.

Blueberry, hailed as an antioxidant superfood, is the fruit of small shrubs in the genus Vaccinium (family Ericaceae). The fruits are a rich source of vitamins, minerals and antioxidants such as flavonoids and phenolic acids. The antioxidative and anti-inflammatory activities derived from the polyphenolic compounds, particularly from the abundantly present anthocyanin pigment, have been highlighted as the major contributing factor to the health-benefitting properties of blueberry. In recent years, blueberry cultivation under polytunnels has expanded, with plastic covers designed to offer protection of crop and fruit yield from suboptimal environmental conditions and birds. An important consideration is that the covers reduce photosynthetically active radiation (PAR) and filter out ultraviolet (UV) radiation that is critical for the fruit’s bioactive composition. Blueberry fruits grown under covers have been reported to have reduced antioxidant capacity as compared to fruits from open fields. In addition to light, abiotic stresses such as salinity, water deficit, and low temperature trigger accumulation of antioxidants. We highlight in this review how interventions such as light-emitting diodes (LEDs), photo-selective films, and exposure of plants to mild stresses, alongside developing new varieties with desired traits, could be used to optimise the nutritional quality, particularly the content of polyphenols, of blueberry grown under covers.

Abstract Cardiac magnetic resonance (CMR) is emerging as an important tool in the assessment of heart failure with preserved ejection fraction (HFpEF). This study sought to investigate the prognostic value of multiparametric CMR, including left and right heart volumetric assessment, native T1-mapping and LGE in HFpEF. In this retrospective study, we identified patients with HFpEF who have undergone CMR. CMR protocol included: cines, native T1-mapping and late gadolinium enhancement (LGE). The mean follow-up period was 3.2 ± 2.4 years. We identified 86 patients with HFpEF who had CMR. Of the 86 patients (85% hypertensive; 61% males; 14% cardiac amyloidosis), 27 (31%) patients died during the follow up period. From all the CMR metrics, LV mass (area under curve [AUC] 0.66, SE 0.07, 95% CI 0.54–0.76, p = 0.02), LGE fibrosis (AUC 0.59, SE 0.15, 95% CI 0.41–0.75, p = 0.03) and native T1-values (AUC 0.76, SE 0.09, 95% CI 0.58–0.88, p 133.24 g (hazard ratio [HR] 1.58, 95% CI 1.1–2.2, p 34.86% (HR 1.77, 95% CI 1.1–2.8, p = 0.01) and native T1 > 1056.42 ms (HR 2.36, 95% CI 0.9–6.4, p = 0.07). In multivariate cox regression, CMR score model comprising these three variables independently predicted mortality in HFpEF when compared to NTproBNP (HR 4 vs HR 1.65). In non-amyloid HFpEF cases, only native T1 > 1056.42 ms demonstrated higher mortality (AUC 0.833, p

Introduction Digital footprint records -- the tracks and traces amassed by individuals as a result of their interactions with the internet, digital devices and services -- can provide ecologically valid data on individual behaviours. These could enhance longitudinal population study databanks; but few UK longitudinal studies are attempting this. When using novel sources of data, study managers must engage with participants in order to develop ethical data processing frameworks that facilitate data sharing whilst safeguarding participant interests. Objectives This paper aims to summarise the participant involvement approach used by the ALSPAC birth cohort study to inform the development of a framework for using linked participant digital footprint data, and provide an exemplar for other data linkage infrastructures. Methods The paper synthesises five qualitative forms of inquiry. Thematic analysis was used to code transcripts for common themes in relation to conditions associated with the acceptability of sharing digital footprint data for longitudinal research. Results We identified six themes: participant understanding; sensitivity of location data; concerns for third parties; clarity on data granularity; mechanisms of data sharing and consent; and trustworthiness of the organisation. For cohort members to consider the sharing of digital footprint data acceptable, they require information about the value, validity and risks; control over sharing elements of the data they consider sensitive; appropriate mechanisms to authorise or object to their records being used; and trust in the organisation. Conclusion Realising the potential for using digital footprint records within longitudinal research will be subject to ensuring that this use of personal data is acceptable; and that rigorously controlled population data science benefiting the public good is distinguishable from the misuse and lack of personal control of similar data within other settings. Participant co-development informs the ethical-governance framework for these novel linkages in a manner which is acceptable and does not undermine the role of the trusted data custodian.

Abstract Background What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL). Method The Analysis of Teaching of Medical Schools (AToMS) survey used detailed timetables provided by 25 schools with standard 5-year courses. Timetabled teaching events were coded in terms of course year, duration, teaching format, and teaching content. Ten schools used PBL. Teaching times from timetables were validated against two other studies that had assessed GP teaching and lecture, seminar, and tutorial times. Results A total of 47,258 timetabled teaching events in the academic year 2014/2015 were analysed, including SSCs (student-selected components) and elective studies. A typical UK medical student receives 3960 timetabled hours of teaching during their 5-year course. There was a clear difference between the initial 2 years which mostly contained basic medical science content and the later 3 years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2 years. Medical schools differed in duration, format, and content of teaching. Two main factors underlay most of the variation between schools, Traditional vs PBL teaching and Structured vs Unstructured teaching. A curriculum map comparing medical schools was constructed using those factors. PBL schools differed on a number of measures, having more PBL teaching time, fewer lectures, more GP teaching, less surgery, less formal teaching of basic science, and more sessions with unspecified content. Discussion UK medical schools differ in both format and content of teaching. PBL and non-PBL schools clearly differ, albeit with substantial variation within groups, and overlap in the middle. The important question of whether differences in teaching matter in terms of outcomes is analysed in a companion study (MedDifs) which examines how teaching differences relate to university infrastructure, entry requirements, student perceptions, and outcomes in Foundation Programme and postgraduate training.

Abstract Background Medical schools differ, particularly in their teaching, but it is unclear whether such differences matter, although influential claims are often made. The Medical School Differences (MedDifs) study brings together a wide range of measures of UK medical schools, including postgraduate performance, fitness to practise issues, specialty choice, preparedness, satisfaction, teaching styles, entry criteria and institutional factors. Method Aggregated data were collected for 50 measures across 29 UK medical schools. Data include institutional history (e.g. rate of production of hospital and GP specialists in the past), curricular influences (e.g. PBL schools, spend per student, staff-student ratio), selection measures (e.g. entry grades), teaching and assessment (e.g. traditional vs PBL, specialty teaching, self-regulated learning), student satisfaction, Foundation selection scores, Foundation satisfaction, postgraduate examination performance and fitness to practise (postgraduate progression, GMC sanctions). Six specialties (General Practice, Psychiatry, Anaesthetics, Obstetrics and Gynaecology, Internal Medicine, Surgery) were examined in more detail. Results Medical school differences are stable across time (median alpha = 0.835). The 50 measures were highly correlated, 395 (32.2%) of 1225 correlations being significant with p

Cancer therapy has evolved from being broadly directed towards tumor types, to highly specific treatment protocols that target individual molecular subtypes of tumors. With the ever-increasing data on imaging characteristics of tumor subtypes and advancements in imaging techniques, it is now often possible for radiologists to differentiate tumor subtypes on imaging. Armed with this knowledge, radiologists may be able to provide specific information that can obviate the need for invasive methods to identify tumor subtypes. Different tumor subtypes also differ in their patterns of metastatic spread. Awareness of these differences can direct radiologists to relevant anatomical sites to screen for early metastases that may otherwise be difficult to detect during cursory inspection. Likewise, this knowledge will help radiologists to interpret indeterminate findings in a more specific manner.

Novel anticancer agents have replaced conventional chemotherapy as first line agents for many cancers, with continued new and expanding indications. Small molecule inhibitors act on cell surface or intracellular targets and prevent the downstream signaling that would otherwise permit tumor growth and spread. Anticancer antibodies can be directed against growth factors or may be immunotherapeutic agents. The latter act by inhibiting mechanisms that cancer cells use to evade the immune system. Hormonal agents act by decreasing levels of hormones that are necessary for the growth of certain cancer cells. Cancer therapy protocols often include novel anticancer agents and conventional chemotherapy used successively or in combination, in order to maximize survival and minimize morbidity. A working knowledge of anti-cancer drug classification will aid the radiologist in assessing response on imaging.

The past decade has witnessed a change in landscape of cancer management with the advent of precision oncology. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and have played an important role in improving patient survival. While the patients are living longer, treatment with ICIs are sometimes associated with adverse effects, some of which could be fatal. Radiologists can play a crucial role by early identification of some of these adverse effects during restaging scans. Our paper focuses on the imaging features of commonly occurring ICI toxicities based on organ system.

The female flowers of the Humulus lupulus plant or Hops have been used extensively within the brewing industry for their aroma and bitterness properties. It was also found that beer that contained hops was less likely to spoil, thus revealing the antimicrobial potential of these plants. One species of bacteria, Mycobacterium spp., is of particular interest as it is the causative agent of both human and animal forms of tuberculosis (TB). In this study an aqueous extraction process was employed to analyse the antibacterial properties of 50 hop extracts (45 individual variants); against M. bovis BCG. Using an agar well diffusion assay we found that all hops exhibited a level of inhibitory activity which ranged from 1.2 mm (+/− 0.08 mm) in the case of hop variant; Target, to 15.7 mm (+/− 0.45 mm) in the case of hop variant Citra. The Citra variant had a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 16% v/v. This is the first study to analyse a wide range of hops for their antimicrobial potential against M. bovis BCG and recommends that further research focuses on other Mycobacteria spp., the potential for antimicrobial synergy and the antibacterial effect of individual components.

Congenital anomalies (CAs) are structural or functional disorders that occur during intrauterine life. Longitudinal cohort studies provide unique opportunities to investigate potential causes and consequences of these disorders. In this data note, we describe how we identified cases of major CAs, with a specific focus on congenital heart diseases (CHDs), in the Avon Longitudinal Study of Parents and Children (ALSPAC). We demonstrate that combining multiple sources of data including data from antenatal, delivery, primary and secondary health records, and parent-reported information can improve case ascertainment. Our approach identified 590 participants with a CA according to the European Surveillance of Congenital Anomalies (EUROCAT) guidelines, 127 of whom had a CHD. We describe the methods that identified these cases and provide statistics on subtypes of anomalies. The data note contains details on the processes required for researchers to access these data.

Background Discharge summaries need to be completed in a timely manner, to improve communication between primary and secondary care, and evidence suggests that delays in discharge summary completion can lead to patient harm.Following a hospital health and safety review due to the sheer backlog of notes in the doctor’s room and wards, urgent action had to be undertaken to improve the discharge summary completion process at our hospital’s paediatric assessment unit. It was felt that the process would best be carried out within a quality improvement (QI) project.Methods Kotter’s ‘eight-step model for change’ was implemented in this QI project with the aim to clear the existing backlog of pending discharge summaries and improve the timeliness of discharge summary completion from the hospital’s paediatric assessment unit. A minimum target of 10% improvement in the completion rate of discharge summaries was set as the primary goal of the project.Results Following the implementation of the QI processes, we were able to clear the backlog of discharge summaries within 9 months. We improved completion within 24 hours, from

Avian schistosomes are blood flukes parasitizing aquatic birds and snails, which are responsible for a zoonotic disease known as cercarial dermatitis, a hypersensitive reaction associated to the cutaneous penetration of furcocercariae. Despite its worldwide distribution, its knowledge is fragmentary in the Neotropics, with most of data coming from Argentina and Brazil. In Chile, there are only two mentions of these parasites from birds, and one human outbreak was associated to the genus “Trichobilharzia”. However, the identity of such parasites is pending. The aim of this study was to identify the furcocercariae of avian schistosomes from Southern Chile using an integrative approach. Thus, a total of 2283 freshwater snails from different families were collected from three different regions. All snails were stimulated for the shedding of furcocercariae, but only Chilina dombeyana (Chilinidae) from the Biobío region was found to be parasitized. The morphology and phylogenetic analyses of 28S and COI genes stated two lineages, different from Trichobilharzia, shared with Argentina. This study provides new information on Neotropical schistosomes, highlighting the need for major research on these neglected trematodes, which are considered to be emerging/re-emerging parasites in other parts of the globe as consequence of anthropogenic disturbances and climatic change. Highlights: 1. Two different lineages (Lineage I and II) were described and molecularly characterized (28S and COI genes); 2. Cercaria chilinae I y II are proposed as a synonymous of Lineage II. Thus, a total of four different lineages of avian schistosomes are related to Chilina spp.; 3. Chilina spp. represents an important intermediate host for avian schistosomes in South America, constituting a reservoir de schistosomes with zoonotic potential; 4. Coinfection between the two different lineages was found, a finding previously not reported for avian schistosomes; 5. Expansion in the geographic distribution of Nasusbilharzia melancorhypha from its original record in Argentina, with Chilina dombeyana as an additional intermediate host.

Congenital anomalies (CAs) are structural or functional disorders that occur during intrauterine life. Longitudinal cohort studies provide unique opportunities to investigate potential causes and consequences of these disorders. In this data note, we describe how we identified cases of major CAs, with a specific focus on congenital heart diseases (CHDs), in the Avon Longitudinal Study of Parents and Children (ALSPAC). We demonstrate that combining multiple sources of data including data from antenatal, delivery, primary and secondary health records, and parent-reported information can improve case ascertainment. Our approach identified 590 participants with a CA according to the Euro Registers of Congenital Anomalies (EUROCAT) guidelines, 127 of whom had a CHD. We describe the methods that identified these cases and provide statistics on subtypes of anomalies. The data note contains details on the processes required for researchers to access these data.

This study aims to illustrate the impact of adopting Regulatory technology (RegTech) innovations in banks on money laundering prevention effectiveness using Bahrain as a case study. Bahrain has strived to position itself as the banking center of the Arabian Gulf, hence the results of this novel research are informative of the practices in the region. The primary data for this study was collected through a survey instrument distributed to 100 bankers working in Bahrain with expertise in compliance. The results of multivariate analysis indicate that transactions monitoring through RegTech and cost- and time-saving aspects of RegTech, drive money laundering prevention effectiveness to a highly statistically significant extent. However, electronic know your customer (KYC) technologies are insignificant as drivers. This research not only sheds light on the efficacy of RegTech but also raises general awareness concerning the adoption and integration of RegTech platforms for fighting money laundering. In particular, the findings provide specific insights about the deployment of RegTech capabilities in banks in regional banking centers of modest scale.

Abstract The Neotropic cormorant Nannopterum (Phalacrocorax) brasilianus (Suliformes: Phalacrocoracidae) is widely distributed in Central and South America. In Chile, information about parasites for this species is limited to helminths and nematodes, and little is known about other parasite groups. This study documents the parasitic fauna present in 80 Neotropic cormorants’ carcasses collected from 2001 to 2008 in Antofagasta, Biobío, and Ñuble regions. Birds were externally inspected for ectoparasites and necropsies were performed to examine digestive and respiratory organs in search of endoparasites. Ectoparasites collected were cleared and mounted for identification under a microscope. Fecal samples were also evaluated to determine the presence of protozoan parasites employing a flotation technique. A total of 44 (42.5%) of birds were infested with at least one ectoparasite species, while 77 (96.25%) were carrying endoparasites. No protozoan forms were found after examination. Most prevalent endoparasite species found were Contracaecum rudolphii s. l. (72/80, 90%), followed by Pectinopygus gyroceras (33/80, 41.25%), and Profilicollis altmani (26/80, 32.5%). This is the first report of P. altmani, Baruscapillaria carbonis, Avioserpens sp., Cyathostoma (Cyathostoma) phenisci, and Eidmaniella pelucida in the Neotropic cormorant. These findings also expand the distributional range of Andracantha phalacrocoracis, Paradilepis caballeroi, Hysteromorpha triloba, and P. gyroceras to Chile.

Background: Residing in greener areas is increasingly linked to beneficial health outcomes, but little is known about its effect on respiratory health. Objective: We examined associations between residential greenness and nearby green spaces with lung function up to 24 years in the UK Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Methods: Lung function was measured by spirometry at eight, 15 and 24 years of age. Greenness levels within circular buffers (100–1000 m) around the birth, eight-, 15- and 24-year home addresses were calculated using the satellite-derived Normalized Difference Vegetation Index and averaged (lifetime greenness). The presence and proportion of green spaces (urban green spaces, forests and agricultural land) within a 300 m buffer was determined. First, associations between repeated greenness and green space variables and repeated lung function parameters were assessed using generalized estimation equations (N = 7094, 47.9% male). Second, associations between lifetime average greenness and lifetime average proportion of green spaces with lung function at 24-years were assessed using linear regression models (N = 1763, 39.6% male). All models were adjusted for individual and environmental covariates. Results: Using repeated greenspace and lung function data at eight, 15 and 24 years, greenness in a 100 m buffer was associated with higher FEV1 and FVC (11.4 ml [2.6, 20.3] and 12.2 ml [1.8, 22.7], respectively, per interquartile range increase), as was the presence of urban green spaces in a 300 m buffer (20.3 ml [−0.1, 40.7] and 23.1 ml [-0.3, 46.5] for FEV1 and FVC, respectively). These associations were independent of air pollution, urbanicity and socio-economic status. Lifetime average greenness within a 100 m buffer and proportion of agricultural land within a 300 m buffer were associated with better lung function at 24 years but adjusting for asthma attenuated these associations. Discussion: This study provides suggestive evidence that children whose homes are in more vegetated places or are in close proximity of green spaces have better lung function up to 24 years of age.

Despite the growing number of biologic and JAK inhibitor therapeutic agents available to treat various systemic autoimmune illnesses, the lack of a validated companion diagnostic (CDx) to accurately predict drug responsiveness for an individual results in many patients being treated for years with expensive, ineffective, or toxic drugs. This review will focus primarily on rheumatoid arthritis (RA) therapeutics where the need is greatest due to poor patient outcomes if the optimum drug is delayed. We will review current FDA-approved biologic and small molecule drugs and why RA patients switch these medications. We will discuss the sampling of various tissues for potential CDx and review early results from studies investigating drug responsiveness utilizing advanced technologies including; multiplex testing of cytokines and proteins, autoantibody profiling, genomic analysis, proteomics, miRNA analysis, and metabolomics. By using these new technologies for CDx the goal is to improve RA patient outcomes and achieve similar successes like those seen in oncology using precision medicine guided therapeutics.

Background: Radon (and its decay products) is a known human carcinogen and the leading cause of lung cancer in never-smokers and the second in ever-smokers. The carcinogenic mechanism from radiation is a combination of genetic and epigenetic processes, but compared to the genetic mechanisms, epigenetic processes remain understudied in humans. This study aimed to explore associations between residential radon exposure and DNA methylation in the general population. Methods: Potential residential radon exposure for 75-metre area buffers was linked to genome-wide DNA methylation measured in peripheral blood from children and mothers of the Accessible Resource for Integrated Epigenomic Studies subsample of the ALSPAC birth cohort. Associations with DNA methylation were tested at over 450,000 CpG sites at ages 0, 7 and 17 years (children) and antenatally and during middle-age (mothers). Analyses were adjusted for potential residential and lifestyle confounding factors and were determined for participants with complete data (n = 786 to 980). Results: Average potential exposure to radon was associated in an exposure-dependent manner with methylation at cg25422346 in mothers during pregnancy, with no associations at middle age. For children, radon potential exposure was associated in an exposure-dependent manner with methylation of cg16451995 at birth, cg01864468 at age 7, and cg04912984, cg16105117, cg23988964, cg04945076, cg08601898, cg16260355 and cg26056703 in adolescence. Conclusions: Residential radon exposure was associated with DNA methylation in an exposure-dependent manner. Although chance and residual confounding cannot be excluded, the identified associations may show biological mechanisms involved in early biological effects from radon exposure.

Introduction:The consequences of low partial pressure of O2 include low arterial O2 saturations (SaO2), low blood O2 content (CaO2), elevated mean pulmonary artery pressure (PAP), and decreased O2 consumption VO2. 5-hydroxymethyl-2-furfural (5-HMF) binds to the N-terminal valine of hemoglobin (HgB) and increases its affinity to O2. We used an instrumented, sedated swine model to study the effect of 5-HMF on cardiovascular parameters during exposure to acute normobaric hypoxia (NH).MethodsTwenty-three sedated and instrumented swine were randomly assigned to one of three treatment groups and received equal volume of normal saline (VEH), 20 mg/kg 5-HMF (5-HMF-20) or 40 mg/kg 5-HMF (5-HMF-40). Animals then breathed 10% FiO2 for 120 min. Parameters recorded were Cardiac Output (CO), Mean Arterial Blood Pressure (MAP), Heart Rate (HR), Mean Pulmonary Artery Pressure (PAP), SaO2 and saturation of mixed venous blood (SvO2). The P50 was measured at fixed time intervals prior to and during NH.Results5-HMF decreased P50. In the first 30 min of NH, treatment with 5-HMF-20 and 5-HMF-40 resulted in a (1) significantly smaller decrement in SaO2 and SvO2, (2) significantly lower HR and CO, and (3) smaller increase in PAP compared to VEH. In the 120 min of NH there was a trend toward improved mortality with 5-HMF treatment.Conclusion5-HMF treatment decreased P50, improved SaO2, and mitigated increases in PAP in this swine model of NH.

Background: Radon (and its decay products) is a known human carcinogen and the leading cause of lung cancer in never-smokers and the second in ever-smokers. The carcinogenic mechanism from radiation is a combination of genetic and epigenetic processes, but compared to the genetic mechanisms, epigenetic processes remain understudied in humans. This study aimed to explore associations between residential radon exposure and DNA methylation in the general population. Methods: Potential residential radon exposure for 75-metre area buffers was linked to genome-wide DNA methylation measured in peripheral blood from children and mothers of the Accessible Resource for Integrated Epigenomic Studies subsample of the ALSPAC birth cohort. Associations with DNA methylation were tested at over 450,000 CpG sites at ages 0, 7 and 17 years (children) and antenatally and during middle-age (mothers). Analyses were adjusted for potential residential and lifestyle confounding factors and were determined for participants with complete data (n = 786-980). Results: Average potential exposure to radon was associated in an exposure-dependent manner with methylation at cg25422346 in mothers during pregnancy, with no associations at middle age. For children, radon potential exposure was associated in an exposure-dependent manner with methylation of cg16451995 at birth, cg01864468 at age 7, and cg04912984, cg16105117, cg23988964, cg04945076, cg08601898, cg16260355 and cg26056703 in adolescence. Conclusions: Residential radon exposure was associated with DNA methylation in an exposure-dependent manner. Although residual confounding cannot be excluded, the identified associations may show biological mechanisms involved in early biological effects from radon exposure.

Across medieval Europe, cattle commanded a major, if shifting, economic and social value, and their use for meat, milk, and traction is well established. Although the changing roles of cattle throughout this period may have influenced relationships between humans and cattle, this has been largely neglected in historical and zooarchaeological studies. Data from nearly 700 archaeological assemblages of animal remains have been used to provide an overview of the herd structures (age and sex) of cattle populations for England between AD 450 and 1400. These have been analysed alongside pathological and sub-pathological changes in over 2800 lower limb bones of cattle from seventeen archaeological sites to provide a better understanding of the use of cattle for ploughing, hauling, and carting. The findings were considered alongside historical documents and ethnographic evidence to chart changing human–cattle relationships. Results indicate that human–cattle relations varied with changing economic, agricultural, and social practices. From the mid-fifth century, cattle were a form of portable wealth, however, by the mid-ninth century, they were perceived as a commodity with monetary value. From this period, close human–cattle bonds are likely to have been widespread between plough hands and working animals. Such bonds are may have diminished with the increasing number of young beef cattle kept to supply the urban population from the mid-eleventh century.