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Abstract Evasion of cell death is a hallmark of cancer, and consequently the induction of cell death is a common strategy in cancer treatment. However, the molecular mechanisms regulating different types of cell death are poorly understood. We have formerly shown that in the epidermis of hypomorphic zebrafish hai1a mutant embryos, pre-neoplastic transformations of keratinocytes caused by unrestrained activity of the type II transmembrane serine protease Matriptase-1 heal spontaneously. This healing is driven by Matriptase-dependent increased sphingosine kinase (SphK) activity and sphingosine-1-phosphate (S1P)-mediated keratinocyte loss via apical cell extrusion. In contrast, amorphic hai1a fr26 mutants with even higher Matriptase-1 and SphK activity die within a few days. Here we show that this lethality is not due to epidermal carcinogenesis, but to aberrant tp53-independent apoptosis of keratinocytes caused by increased levels of pro-apoptotic C16 ceramides, sphingolipid counterparts to S1P within the sphingolipid rheostat, which severely compromises the epidermal barrier. Mathematical modelling of sphingolipid rheostat homeostasis, combined with in vivo manipulations of components of the rheostat or the ceramide de novo synthesis pathway, indicate that this unexpected overproduction of ceramides is caused by a negative feedback loop sensing ceramide levels and controlling ceramide replenishment via de novo synthesis. Therefore, despite their initial decrease due to increased conversion to S1P, ceramides eventually reach cell death-inducing levels, making transformed pre-neoplastic keratinocytes die even before they are extruded, thereby abrogating the normally barrier-preserving mode of apical live cell extrusion. Our results offer an in vivo perspective of the dynamics of sphingolipid homeostasis and its relevance for epithelial cell survival versus cell death, linking apical cell extrusion and apoptosis. Implications for human carcinomas and their treatments are discussed.

Abstract Understanding self-organized pattern formation is fundamental to biology. In 1952, Alan Turing proposed a pattern-enabling mechanism in reaction-diffusion systems containing chemical species later conceptualized as activators and inhibitors that are involved in feedback loops. However, identifying pattern-enabling regulatory systems with the concept of feedback loops has been a long-standing challenge. To date, very few pattern-enabling circuits have been discovered experimentally. This is in stark contrast to ubiquitous periodic patterns and symmetry in biology. In this work, we systematically study Turing patterns in 23 elementary biochemical networks without assigning any activator or inhibitor. These mass action models describe post-synthesis interactions applicable to most proteins and RNAs in multicellular organisms. Strikingly, we find ten simple reaction networks capable of generating Turing patterns. While these network models are consistent with Turing’s theory mathematically, there is no apparent connection between them and commonly used activator-feedback intuition. Instead, we identify a unifying network motif that enables Turing patterns via regulated degradation pathways with flexible diffusion rate constants of individual molecules. Our work reveals widespread biochemical systems for pattern formation, and it provides an alternative approach to tackle the challenge of identifying pattern-enabling biological systems.

AbstractIn this study, asymptotic formulas for complex order Tangent, Tangent-Bernoulli, and Tangent-Genocchi polynomials are obtained through the method of contour integration, strategically avoiding branch cuts in the process. By employing this technique, the paper elucidates the behavior of these polynomials in the complex plane. Additionally, the investigation expands upon the Taylor series expansion of these functions, revealing alternative asymptotic expansions. This dual approach not only enhances our understanding of the asymptotic properties of these polynomials but also offers alternative mathematical perspectives, enriching the existing body of knowledge in this field.

Abstract Hard ticks (Acari: Ixodidae) have been historically identified by morphological methods which require highly specialized expertise and more recently by DNA-based molecular assays that involve high costs. Although both approaches provide complementary data for tick identification, each method has limitations which restrict their use on large-scale settings such as regional or national tick surveillance programs. To overcome those obstacles, the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been introduced as a cost-efficient method for the identification of various organisms, as it balances performance, speed, and high data output. Here we describe the use of this technology to validate the distinction of two closely related Dermacentor tick species based on the development of the first nationwide MALDI-TOF MS reference database described to date. The dataset obtained from this protein-based approach confirms that tick specimens collected from United States regions west of the Rocky Mountains and identified previously as Dermacentor variabilis are the recently described species, Dermacentor similis. Therefore, we propose that this integrative taxonomic tool can facilitate vector and vector-borne pathogen surveillance programs in the United States and elsewhere.

Bertiella spp. is a mite-borne cestode parasite that inhabits the small intestine of wide range of mammals, including non-human primates. In the present study, the morphological and molecular analysis of Bertiella studeri recovered from the small intestine of a bonnet macaque (Macaca radiata) from Wayanad, Kerala (South India) was performed. Acetic alum carmine staining identified the cestode morphologically based on the characters like broader proglottids, which contain irregularly alternating genital pores, single set of reproductive organs, 280 testes and a tubular transverse uterus. Molecular characterization was done using 18SrRNA, ITS1-5.8S and COX1 genes. Phylogenetic trees were constructed using MEGA X based on the Maximum Likelihood (ML) method (Hasegawa-Kishino-Yano (HKY) model). Cytochrome oxidase I gene could detect the existence of genetic variation in the parasite from two different hosts viz., monkey (Kerala, Argentina, and Kenya) and human (Sri Lanka). A minimum spanning network of haplotypes was generated by the haplotype networking with the above sequences using the popARTv1.7. Haplotype analysis based on COX1 revealed that the parasite haplotype was different in each country with highest population frequency in Sri Lanka.

Abstract Macrophages provide a crucial environment for Salmonella enterica serovar Typhi (S. Typhi) to multiply during typhoid fever, yet our understanding of how human macrophages and S. Typhi interact remains limited. In this study, we delve into the dynamics of S. Typhi replication within human macrophages and the resulting heterogeneous transcriptomic responses of macrophages during infection. Our study reveals key factors that influence macrophage diversity, uncovering distinct immune and metabolic pathways associated with different stages of S. Typhi intracellular replication in macrophages. Of note, we found that macrophages harboring replicating S. Typhi are skewed towards an M1 pro-inflammatory state, whereas macrophages containing non-replicating S. Typhi exhibit neither a distinct M1 pro-inflammatory nor M2 anti-inflammatory state. Additionally, macrophages with replicating S. Typhi were characterized by the increased expression of genes associated with STAT3 phosphorylation and the activation of the STAT3 transcription factor. Our results shed light on transcriptomic pathways involved in the susceptibility of human macrophages to intracellular S. Typhi replication, thereby providing crucial insight into host phenotypes that restrict and support S. Typhi infection.

Background In the UK, one in four patients are in work at the time of their hip or knee replacement surgery. These patients receive little support about their return to work (RTW). There is a need for an occupational support intervention that encourages safe and sustained RTW which can be integrated into National Health Service practice. We developed a two-arm intervention trial, based on a feasibility study, to assess whether an occupational support intervention (the OPAL (Occupational support for Patients undergoing Arthroplasty of the Lower limb) intervention) is effective in supporting a reduced time to full, sustained RTW compared with usual care in patients undergoing hip and knee replacement.Methods and analysis This is a multicentre, individually randomised controlled superiority trial comparing the OPAL intervention to usual care. 742 working adults listed for elective primary hip or knee replacement, who intend to RTW, will be randomised to the OPAL intervention or usual care. The intervention comprises: (1) multimedia information resources; and (2) support from a designated RTW coordinator. The primary outcome is time until ‘full’ sustained RTW without sick leave for a consecutive 4-week period. Secondary outcomes are: time to any RTW, measures of functional recovery, number of ‘sick days’ between surgery and ‘full’ sustained RTW and the use of workplace modifications to facilitate their return. A health economic evaluation and a mixed methods process evaluation will assess cost-effectiveness and the implementation, fidelity and acceptability of the intervention, respectively. Outcomes will be collected at baseline, 3, 6, 9 and 12-month follow-up time points, as well as a monthly RTW questionnaire.Ethics and dissemination Dissemination will focus on supporting the wider adoption and implementation of the intervention (if effective) and will target groups for whom the results will be relevant. This trial was approved by West Midlands—Edgbaston REC 23/WM/0013.Trial registration number ISRCTN13694911.

A 28-year-old female, a known case of neurofibromatosis 1, presented to the respiratory medicine department with complaints of breathlessness and cough for 2 weeks’ duration. Clinical examination revealed right-sided moderate pleural effusion. Computed tomography (CT) chest revealed a large anterior mediastinal mass with chest wall infiltration. Histopathology showed neoplasm with epithelioid cells, arranged as sheets and interlacing spindle cells with a moderate amount of eosinophilic cytoplasm and inconspicuous nucleoli. Histopathological examination of excised specimen showed a malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation also known as malignant triton tumor. After palliative chemotherapy, later on follow-up, CT-guided biopsy from right side chest wall lesion also showed the same. Because of this rare presentation, we are reporting this case.

Immunoglobulin G4-related Disease (IgG4-RD) is an immune-mediated fibroinflammatory disease that affects multiple organs, resulting in tumefactive lesions and/or organ dysfunction. This chronic, multiorgan inflammatory process is characterised by the infiltration of IgG4-positive plasma cells and has a variable clinical presentation depending on the organ involved. The present case series discusses four cases (two males and two females) of IgG4-RD involving different sites in patients presented to present Institution. The authors reviewed four cases of IgG4-RD, including clinical details, biochemical, radiological, and histopathological features. The case series includes IgG4-RD masquerading as meningioma, IgG4-related sclerosing cholangitis, IgG4-RD of the thyroid gland, and IgG4-RD of the lacrimal gland. Since IgG4-RD has non specific clinical features, histopathological analysis and immunohistochemistry play a pivotal role in diagnosis. Despite its diagnostic difficulties, earlier recognition is crucial to prevent significant morbidity and extensive fibrosis leading to organ failure.

This paper documents the results of an intervention conducted in Nigeria to test the effectiveness of a mobile phone technology, text4life, in enabling women to self-report gender-based violence (GBV). Women experiencing GBV and other challenges related to sexual and reproductive health and rights were requested to use their mobile phones to text a code to a central server. In turn, the server relayed the messages to trained nearby health providers and civil society organization (CSO) officials who reached out to provide health care and social management services to the callers. Interviews were conducted with some callers, health care providers, and CSO staff to explore their experiences with the device. The interviews and data from the server were analyzed qualitatively and quantitatively. The results indicate that over a 27-month period, 3,403 reports were received by the server, 34.9% of which were reporting GBV. While interviewees perceived that a large proportion of the women were satisfied with the use of text4life, and many received medical treatment and psychological care, the consensus opinion was that many women reporting GBV did not wish to pursue police or legal action. This was due to women’s perceptions that there would be negative cultural and social backlash should they pursue civil punishments for their partners. We conclude that a mobile phone device can be used effectively to report GBV in low-resource settings. However, the device would be more useful if it contributes to equitable primary prevention of GBV, rather than secondary prevention measures.

Precision medicine has emerged as a cornerstone in cancer treatment revolutionizing our approach across malignancies. Molecular profiling of biliary tract cancers (BTCs) has changed the treatment landscape positively by prolonging survival in an aggressively fatal malignancy in its advanced stages. The acquisition of tissue tumor DNA for genomic analysis in BTC is often anatomically challenging, limited by quantity and quality. In response, ctDNA has emerged as a noninvasive means of molecular profiling. The utility of both plasma and bile ctDNA has been explored in several studies demonstrating the high mutation detection rates and the ability to isolate targetable mutations when present. In addition, the concordance between plasma and tissue DNA provides validity in utilizing ctDNA results to infer treatment decisions. Analysis of ctDNA in BTC has also provided prognostic information and facilitated evaluation of clonal evolution with ease of serial measurements. Insight into novel mechanisms of resistance to targeted therapies are being uncovered in ctDNA. As research endeavors continue to deepen our understanding in the field particularly in the space of ctDNA surveillance after curative intent, the tremendous progress made so far has enabled integration of ctDNA into the clinical practice of BTCs.

AbstractA drastic decline in the number of students that are enrolled for Engineering is now being experienced in developed as well as developing countries. Learning is becoming boring as a generation brought up on technology is losing the ability to pay attention in traditional classes for a long stretch of time. This has led to the idea that other teaching methods do exist and can be applied in teaching/learning. This work leveraged the use of Digital Game-Based Learning (DGBL) in Engineering classrooms to develop a serious game named LogicHouse Version 1 (LogicHouse-V1 or LogicHouse for short). The game, is a web-based serious game prototype that targets selected topics in Digital Electronics course. This course is a core component of undergraduate curriculum in Electrical & Electronics Engineering, Computer Engineering, Information Technology, Communication Engineering, Computer Science and other related Science Technology Engineering and Mathematics (STEM) courses. LogicHouse involves a virtual broken house where the player has to play the various levels to fix the house and gain points along the way. This game was designed based on the Learning Mechanics-Game Mechanics (LM-GM) model and the Unified Modeling Language (UML). Furthermore, the design was implemented using Adobe Illustrator, Procreate, Unity Engine, C#, Microsoft Azure Playfab and deployed on itch.io. Preliminary evaluation results indicate that students are interested in the game and its application. Based on this, there is a prospect of improved performance in any course in which the game is implemented.

The known intrinsic and polymorphic blaOXA-51-like genes of Acinetobacter baumannii were recently reported in other non-A. baumannii Gram-negative pathogens. Accurate detection of this potentially transferrable carbapenemase gene in the clinical setting is critical. This study developed a loop-mediated isothermal amplification (LAMP) assay targetting multiple alleles of blaOXA-51-like genes. Specifically, an alignment-based primer design, in silico primer screening, and in vitro assay confirmation were conducted. Both in silico and in vitro results revealed the tolerance of the LAMP assay to up to five primer-template mismatches outside the 3′-end primer regions. Within 90 min, the LAMP assay also detected the gene targets in other Gram-negative bacteria with known and novel blaOXA-51-like genes. Finally, it showed a superior limit of detection (as low as 101 CFU/mL) compared with polymerase chain reaction, and high specificity against non-targets. This study developed a highly adaptable LAMP assay to monitor blaOXA-51-like genes in the clinical setting and provided important insights into LAMP primer design and screening.

Background N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of cardiac ventricular wall stress that is incorporated into pulmonary hypertension (PH) risk stratification models. Sendaway sampling may enable patients to perform NT-proBNP tests remotely. This UK-wide study aimed to assess the agreement of sendaway NT-proBNP with standard venous NT-proBNP and to assess the effect of delayed processing.Methods Reference venous NT-proBNP was collected from PH patients. Samples for capillary and venous sendaway tests were collected contemporaneously, mailed to a reference laboratory and processed at 3 and 7 days using a Roche Cobas e411 device. Differences in paired measurements were analysed with Passing-Bablok regression, percentage difference plots and the % difference in risk strata.Results 113 patients were included in the study. 13% of day 3 capillary samples were insufficient. Day 3 capillary samples were not equivalent to reference samples (Passing Bablok analysis slope of 0.91 (95% CI 0.88 to 0.93) and intercept of 6.0 (95% CI 0.2 to 15.9)). The relative median difference was −7% and there were acceptable limits of agreement. Day 3 capillary NT-proBNP accurately risk stratified patients in 93.5% of cases. By comparison, day 3 venous results accurately risk stratified patients in 90.1% of cases and were equivalent by Passing-Bablok regression. Delayed sampling of sendaway tests led to an unacceptable level of agreement and systematically underestimated NT-proBNP.Conclusions Sendaway NT-proBNP sampling may provide an objective measure of right ventricular strain for virtual PH clinics. Results must be interpreted with caution in cases of delayed sampling.

In this paper, we outline our qualitative protocol for the largest, independent, mixed-method, evaluation of the High Volume-Low Complexity Surgical Hubs programme in England – The MEASURE study. In addition to serving as a protocol paper, we outline the key methodological considerations and adaptations that are needed when designing big qualitative studies – complex (multi-site, multi-stakeholder), multi-method (e.g. interviews, observations, documents) qualitative research involving a large number of participations ( n = 100+). This paper expands on our previous methodological work, where we used our experience of undertaking a big qualitative study as part of a mixed-method evaluation of a national emergency care-based initiative, to outline the methodological considerations and uncertainties for designing and analysing “big” qualitative studies. In this paper, we put these considerations into practice by providing a transparent account of our qualitative study design. The methodological reflections which we present are centred around the areas where we feel there is the most uncertainty for big qualitative research: study design, sampling (of case sites and stakeholders) and analysis. Underpinning this uncertainty are broader challenges which utilising this approach incite. Namely, that striving for both breadth (national-level insights) and depth (local variation and context), challenges paradigmatic norms and expectations and forces either methodological innovation, or the adaption of existing qualitative methods. We hope this paper provides transparency and insight into an area of qualitative research which has, potentially due to a perception of “safety in numbers” been inherently trusted and rarely scrutinised. Ultimately, we hope that by providing a transparent account of our study design and the challenges we have faced that we continue to encourage discussion and innovation in this evolving area of qualitative research.

Introduction Biological disease-modifying antirheumatic drugs (bDMARDs) have revolutionised the treatment of inflammatory arthritis (IA). However, many people with IA still require planned orthopaedic surgery to reduce pain and improve function. Currently, bDMARDs are withheld during the perioperative period due to potential infection risk. However, this predisposes patients to IA flares and loss of disease control. The question of whether to stop or continue bDMARDs in the perioperative period has not been adequately addressed in a randomised controlled trial (RCT).Methods and analysis PERISCOPE is a multicentre, superiority, pragmatic RCT investigating the stoppage or continuation of bDMARDs. Participants will be assigned 1:1 to either stop or continue their bDMARDs during the perioperative period. We aim to recruit 394 adult participants with IA. Potential participants will be identified in secondary care hospitals in the UK, screened by a delegated clinician. If eligible and consenting, baseline data will be collected and randomisation completed. The primary outcome will be the self-reported PROMIS-29 (Patient Reported Outcome Measurement Information System) over the first 12 weeks postsurgery. Secondary outcome measures are as follows: PROMIS - Health Assessment Questionnaire (PROMIS-HAQ), EQ-5D-5L, Disease activity: generic global Numeric Rating Scale (patient and clinician), Self-Administered Patient Satisfaction scale, Health care resource use and costs, Medication use, Surgical site infection, delayed wound healing, Adverse events (including systemic infections) and disease-specific outcomes (according to IA diagnosis). The costs associated with stopping and continuing bDMARDs will be assessed. A qualitative study will explore the patients’ and clinicians’ acceptability and experience of continuation/stoppage of bDMARDs in the perioperative period and the impact postoperatively.Ethics and dissemination Ethical approval for this study was received from the West of Scotland Research Ethics Committee on 25 April 2023 (REC Ref: 23/WS/0049). The findings from PERISCOPE will be submitted to peer-reviewed journals and feed directly into practice guidelines for the use of bDMARDs in the perioperative period.Trial registration number ISRCTN17691638.

Abstract Declining Arctic sea ice is increasing polar bear land use. Polar bears on land are thought to minimize activity to conserve energy. Here, we measure the daily energy expenditure (DEE), diet, behavior, movement, and body composition changes of 20 different polar bears on land over 19–23 days from August to September (2019–2022) in Manitoba, Canada. Polar bears on land exhibited a 5.2-fold range in DEE and 19-fold range in activity, from hibernation-like DEEs to levels approaching active bears on the sea ice, including three individuals that made energetically demanding swims totaling 54–175 km. Bears consumed berries, vegetation, birds, bones, antlers, seal, and beluga. Beyond compensating for elevated DEE, there was little benefit from terrestrial foraging toward prolonging the predicted time to starvation, as 19 of 20 bears lost mass (0.4–1.7 kg•day−1). Although polar bears on land exhibit remarkable behavioral plasticity, our findings reinforce the risk of starvation, particularly in subadults, with forecasted increases in the onshore period.

The satellite-derived surface urban heat island is often not properly distinguished from the in situ derived canopy-layer urban heat island in the field of remote sensing of urban climates. Yet, some studies have investigated their differences, focusing mainly on single urban agglomerations and limited periods. Moreover, a comparison of different urban heat island studies is impeded due to nonstandardized urban classifications. This study analyzes the impact of different definitions of urban and rural on the urban heat island intensity and investigates the differences between the surface and the canopy-layer urban heat island intensities for a long time period and a large number of urban agglomerations compared with most other urban heat island studies. We compare the urban heat island intensities for 91 European urban agglomerations using moderate-resolution imaging spectroradiometer land surface temperature and Netatmo-derived citizen weather station air temperature for the summers (June–August) of 2019–2021. The results show the following: First, the urban heat island types and their differences are significantly impacted by the underlying urban and rural classification. The findings underline that the studies based on different classification schemes should not be compared without considering the methodology. Second, the surface urban heat island is an all-day phenomenon, while the canopy-layer urban heat island is a nocturnal phenomenon and there is a substantial difference between both types during the diurnal cycle. Thus, land surface temperature should not be used as a proxy for the canopy-layer urban heat island. Third, the urban heat island does not indicate absolute temperatures. Intraseasonal changes in urban heat island intensities and urban temperatures can even have a different temporal evolution.

Background: Postnatal care (PNC) encompasses various aspects including recovery from childbirth, newborn care, breastfeeding, and family planning. Although recent guidelines on improving PNC services in low-resource settings focus on the timing and content of PNC services, there is lack of data on these services in Cross River State, Nigeria and most other low-resource settings. Objectives: To determine the pattern and utilization of PNC services among mothers attending the University of Calabar Teaching Hospital, Cross River State, Nigeria. Materials and Methods: A descriptive cross-sectional design was employed. A total of 341 mothers were selected using simple random sampling via balloting with replacement. Data were collected using a self-developed questionnaire and analyzed through descriptive statistics, Chi-square tests, and association analysis. Results: The results indicated that 23.4% of mothers initiated PNC services within 4–14 days after delivery. Mothers arriving for PNC services after receiving PNC health talks had better utilization of PNC services (OR: 1.50, 95% CI: 1.25–1.80). Conversely, postpartum mothers who were observed to be taking iron supplements (OR: 0.72, 95% CI: 0.57–0.91) and malaria drugs (OR: 0.49, 95% CI: 0.38–0.63) were linked to poorer PNC utilization. More than half (52.3%) of the mothers demonstrated poor PNC utilization. Factors negatively influencing utilization of PNC services included long distances to health facilities (OR: 1.50, 95% CI: 1.25–1.80), negative healthcare provider attitudes (OR: 0.73, 95% CI: 0.62–0.85), and lengthy waiting times (OR: 0.79, 95% CI: 0.67–0.93). Conclusion: This study highlights the need for interventions to promote timely and optimal utilization of PNC services. Addressing barriers related to distance, healthcare provider attitudes, and financial constraints are essential to encourage better access and utilization of PNC services. Targeted strategies can ultimately contribute to improved maternal and newborn health outcomes.

Introduction: The burden of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome in Nigeria remains one of the highest in the world, with the country having the highest number of people living with the infection in the West African subregion. Recent estimates put the HIV prevalence rate in Nigeria at 1.9%. In the early years of the HIV epidemic, attention on the reproductive preferences of people living with HIV was not really considered because of the high risk of mortality and few options to reduce mother-to-child transmission. Methodology: A descriptive cross-sectional study was carried out in November 2018 using quantitative and qualitative methods. A total of 400 participants were recruited for the quantitative part of the study and 10 respondents for each of the focus group discussion (FGD) sessions. Data were collected using an interviewer-administered questionnaire and a FGD guide. Frequencies and percentages were determined using descriptive analysis. Univariate analysis was used to explore the association between the outcome variables and the independent variables. The independent variables which showed a significant association in the univariate analysis were further subjected to multivariate analysis. Results: The desire to have children since their HIV diagnosis had been mooted by 255 (63.8%) respondents in the past and 64.5% of the respondents admitted to wanting to have children at some point in the future. More than half of the respondents (61%) currently wanted more children while a significant proportion of the respondents who wanted children (68.4%) wanted more than one child. Conclusion: The study observed that the desire to have children had largely not been affected by the HIV infection as respondents still had a fairly strong desire to continue to have more children in spite of the risks of transmission involved. The study recommended that government and HIV policymakers need to ensure that HIV prevention messages and programmes adopt cultural and socio-economic considerations when designing and planning HIV prevention programmes.

Background: Detecting breast cancer in its early stages remains a significant challenge in the present context and is a leading cause of death among women, primarily due to delayed identification. This paper presents a practical and accurate approach based on deep learning to identify breast cancer in cytology images.Method: The analytical approach leverages knowledge from a related problem through a technique known as transfer learning. Convolutional neural networks (CNNs) are employed due to their remarkable performance on large datasets. Image classification architectures such as Google network (GoogleNet), Visual geographical group network (VGGNet), residual network (ResNet), and dense convolution network (DenseNet) are utilized in this approach. By applying transfer learning, the images are classified into two categories: those containing cancer cells and those without them. The performance of the proposed ensemble method is evaluated using a breast cytology image dataset.Results: The results of our proposed ensemble framework outperform conventional CNN models in terms of precision, recall, and F1 measures, achieving an impressive 86% prediction accuracy. Visual representations of validation graphs for each classifier demonstrate that the ensemble framework surpasses the performance of pre-trained CNN architectures.Conclusion: Combining the outcomes of conventional CNN architectures into an ensemble framework enhances early breast cancer detection, leading to a reduction in mortality through timely medical interventions.

The results of the PISA study in 2018 showed that the mathematics ability of Indonesian students was still in the low performance category. One of the factors that causes this is the lack of student interest in learning mathematics. Interest is very important because it is interest that encourages students to be active and act in learning. This study aims to see whether the application of a smartphone-based discovery learning model can help increase interest in learning mathematics. The research method used is a descriptive qualitative research method using several research instruments. This research was conducted in one of the schools in South Tangerang at the junior high school level. The instruments used by the authors are observation sheets and reflection sheets and mentor feedback sheets. The results of this study concluded that the application of a smartphone-based discovery learning model is able to effect student interest in learning, which is shown by an increased willingness to learn, pleasure in learning, and student participation. BAHASA INDONESIA ABSTRACT: Hasil studi PISA pada 2018 menunjukkan kemampuan matematika siswa Indonesia masih berada dalam kategori low performance. Salah satu faktor yang menyebabkan hal ini adalah kurangnya minat siswa terhadap pembelajaran matematika. Minat menjadi hal yang sangat penting karena minatlah yang mendorong siswa untuk aktif dan bertindak dalam pembelajaran. Penelitian ini bertujuan untuk melihat penerapan model pembelajaran discovery learning berbasis smartphone dapat membantu mengupayakan minat belajar pada pembelajaran matematika. Metode penelitian yang digunakan adalah metode penelitian kualitatif deskriptif dengan menggunakan beberapa instrumen penelitian. Penelitian ini dilakukan di salah satu sekolah swasta di Tangerang Selatan pada jenjang SMP. Instrumen yang digunakan oleh penulis adalah lembar observasi, lembar refleksi, dan lembar umpan balik mentor. Penelitian ini memberikan hasil bahwa penerapan model pembelajaran discovery learning berbasis smartphone mampu mengupayakan minat belajar siswa yang ditunjukkan dengan meningkatnya kemauan untuk belajar, rasa senang siswa dan partisipasi siswa.

This paper presents a comprehensive study in which non-destructive testing utilizing ultrasonic pulse velocity (UPV), considering both pressure (P) waves and shear (S) waves, was used to assess the compressive strength (CS) of rubberized bricks. These innovative bricks were manufactured by blending lime kiln dust (LKD) waste with ground granulated blast furnace slag (GGBFS), sand, and fine waste tire crumb rubber (WTCR). This study introduces mathematical models to explain the relationships between the results of destructive tests (DTs), specifically compression strength (CS) tests, and non-destructive tests (NDTs) employing UPV. These models were subsequently used to conduct validation exercises to accurately predict the strength of the rubberized bricks produced. The outcomes of the validation tests underscore the effectiveness of the UPV method in predicting the CS of rubberized eco-friendly bricks produced using an LKD-GGBFS blend. Importantly, the prediction using the power model exhibited minimal errors, confirming the utility of the UPV method as a reliable tool for assessing the compressive strength of such sustainable construction materials. This research contributes to advancing the field of eco-friendly construction materials and highlights the practical applicability of non-destructive ultrasonic testing in assessing their structural properties.

This study aimed to investigate the behavior of accelerated carbonation-cured laboratory specimens using the ultrasonic non-destructive testing (UNDT) method and compare the results with the destructive testing (DT) method. The materials used in the study included a blend of lime kiln dust and ground granulated blast furnace slag (LKD-GBFS) wastes, natural fine aggregate (sand), and alternative fine aggregates from waste tires. The chemical analysis of the LKD and GBFS samples highlighted them as suitable alternatives to OPC, hence their utilization in the study. A 60:40 (LKD-GBFS) blending ratio and a 1:2 mix design (one part LKD-GBFS blend and two part sand) was considered. The natural fine aggregate was partially replaced with fine waste tire rubber crumbs (TRCs) in stepped increments of 0, 5, and 10% by the volume of the sand. The samples produced were cured using three curing regimens: humid curing (HC), accelerated carbonation curing (ACC) with no water curing (NWC) afterwards, and water curing after carbonation (WC). From the results, an exponential model was developed, which showed a direct correlation between the UNDT and DT results. The developed model is a useful tool that can predict the CS of carbonated samples when cast samples are unavailable. Lastly, a total CO2 uptake of 15,912 g (15.9 kg) was recorded, which underscores ACC as a promising curing technique that can be utilized in the construction industry. This technique will bring about savings in terms of the time required to produce masonry units while promoting a change in the basic assumptions of a safer and cleaner environment.

Objectives To assess whether prednisone use and/or disease activity score (DAS) are associated with the development of hyperglycaemia and diabetes in rheumatoid arthritis (RA).Methods We included 504 non-diabetic early RA patients from the BeSt study (Dutch acronym for treatment strategies). Patients were randomised to four DAS-steered treatment arms and followed for 10 years. The associations between DAS and prednisone use with glucose levels and the occurrence of hyperglycaemia over time were assessed with linear and logistic mixed effects regression models. Development of diabetes was analysed with Cox regression. Sensitivity analyses were performed in patients who had a first episode of hyperglycaemia.Results 31 of 504 patients (6.2%) with a mean age of 54 years developed diabetes during follow-up; 11 of these (35%) had received prior treatment with prednisone. Prednisone use was not associated with development of hyperglycaemia or diabetes after correction for multiple testing in main or sensitivity analyses. In the main analyses, DAS was significantly associated with development of diabetes (HR 1.802 per 1 point DAS increase, 95% CI 1.284 to 2.529) but not with glucose levels nor hyperglycaemia. In patients with previous hyperglycaemia, DAS was associated with glucose levels, recurrence of hyperglycaemia and diabetes.Conclusions In non-diabetic early RA patients, the use of prednisone was not associated with developing hyperglycaemia or diabetes. However, high DAS increased the risk of diabetes. Potential risks associated with prednisone use may have been mitigated by its effect on DAS.

Introduction The waiting list for elective surgery in England recently reached over 7.8 million people and waiting time targets have been missed since 2010. The high-volume low complexity (HVLC) surgical hubs programme aims to tackle the backlog of patients awaiting elective surgery treatment in England. This study will evaluate the impact of HVLC surgical hubs on productivity, patient care and the workforce.Methods and analysis This 4-year project consists of six interlinked work packages (WPs) and is informed by the Consolidated Framework for Implementation Research. WP1: Mapping current and future HVLC provision in England through document analysis, quantitative data sets (eg, Hospital Episodes Statistics) and interviews with national service leaders. WP2: Exploring the effects of HVLC hubs on key performance outcomes, primarily the volume of low-complexity patients treated, using quasi-experimental methods. WP3: Exploring the impact and implementation of HVLC hubs on patients, health professionals and the local NHS through approximately nine longitudinal, multimethod qualitative case studies. WP4: Assessing the productivity of HVLC surgical hubs using the Centre for Health Economics NHS productivity measure and Lord Carter’s operational productivity measure. WP5: Conducting a mixed-methods appraisal will assess the influence of HVLC surgical hubs on the workforce using: qualitative data (WP3) and quantitative data (eg, National Health Service (NHS) England’s workforce statistics and intelligence from WP2). WP6: Analysing the costs and consequences of HVLC surgical hubs will assess their achievements in relation to their resource use to establish value for money. A patient and public involvement group will contribute to the study design and materials.Ethics and dissemination The study has been approved by the East Midlands—Nottingham Research Ethics Committee 23/EM/0231. Participants will provide informed consent for qualitative study components. Dissemination plans include multiple academic and non-academic outputs (eg, Peer-reviewed journals, conferences, social media) and a continuous, feedback-loop of findings to key stakeholders (eg, NHS England) to influence policy development.Trial registration Research registry: Researchregistry9364 (https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/64cb6c795cbef8002a46f115/).

Abstract Background Evidence is needed to support local action to reduce the adverse health impacts of climate change and maximise the health co-benefits of climate action. Focused on England, the study identifies priority areas for research to inform local decision making. Methods Firstly, potential priority areas for research were identified from a brief review of UK policy documents, and feedback invited from public and policy stakeholders. This included a survey of Directors of Public Health (DsPH) in England, the local government officers responsible for public health. Secondly, rapid reviews of research evidence examined whether there was UK evidence relating to the priorities identified in the survey. Results The brief policy review pointed to the importance of evidence in two broad areas: (i) community engagement in local level action on the health impacts of climate change and (ii) the economic (cost) implications of such action. The DsPH survey (n = 57) confirmed these priorities. With respect to community engagement, public understanding of climate change’s health impacts and the public acceptability of local climate actions were identified as key evidence gaps. With respect to economic implications, the gaps related to evidence on the health and non-health-related costs and benefits of climate action and the short, medium and longer-term budgetary implications of such action, particularly with respect to investments in the built environment. Across both areas, the need for evidence relating to impacts across income groups was highlighted, a point also emphasised by the public involvement panel. The rapid reviews confirmed these evidence gaps (relating to public understanding, public acceptability, economic evaluation and social inequalities). In addition, public and policy stakeholders pointed to other barriers to action, including financial pressures, noting that better evidence is insufficient to enable effective local action. Conclusions There is limited evidence to inform health-centred local action on climate change. More evidence is required on public perspectives on, and the economic dimensions of, local climate action. Investment in locally focused research is urgently needed if local governments are to develop and implement evidence-based policies to protect public health from climate change and maximise the health co-benefits of local action.

The global challenge faced due to the impact of the construction industry on climate change, along with the issues surrounding sustainable waste disposal, has necessitated various research on using waste products as eco-friendly alternatives in construction. In this study, the avoidance of waste disposal through landfills in Australia was encouraged by incorporating lime kiln dust (LKD) and tire rubber waste (TRW) into masonry mixes to manufacture green bricks. Furthermore, the investigations in this article highlight the use of mercury intrusion porosimetry (MIP) to determine the durability of the LKD-TRW bricks when exposed to freeze–thaw (F-T) cycles by examining the pore size distribution within the bricks. The LKD waste was blended with ground granulated blast furnace slag (GGBFS) at a 70:30 blending ratio and combined with the TRW in stepped increments of 5% from 0 to 20% to produce these eco-friendly bricks. The compressive strength (CS), flexural strength (FS), frost resistance (FR), pore size distribution according to mercury intrusion porosimetry (MIP), and the water absorption (WA) properties of the bricks were assessed. The CS and FS values at 28 days of curing were recorded as 6.17, 5.25, and 3.09 MPa and 2.52, 2, and 1.55 MPa for 0, 5, and 10% TRW contents, respectively. Durability assessments using the F-T test showed that the bricks produced with 0% TRW passed as frost-resistant bricks. Furthermore, the results from the MIP test showed a total pore volume of 0.033 mL/g at 3 µm pore size for the 0% TRW content, further confirming its durability. Hence, the 0% LKD-TRW bricks can be utilized in cold regions where temperatures can be as low as −43 °C without deteriorating. Lastly, WA values of 7.25, 11.76, and 14.96% were recorded for the bricks with 0, 5, and 10% TRW, respectively, after the 28-day curing period. From all of the results obtained from the laboratory investigations, the LKD-TRW bricks produced with up to 10% TRW were within the satisfactory engineering requirements for masonry units.

Background Supravalvar aortic stenosis (SVAS) is a characteristic feature of Williams–Beuren syndrome (WBS). Its severity varies: ~20% of people with Williams–Beuren syndrome have SVAS requiring surgical intervention, whereas ~35% have no appreciable SVAS. The remaining individuals have SVAS of intermediate severity. Little is known about genetic modifiers that contribute to this variability. Methods and Results We performed genome sequencing on 473 individuals with Williams–Beuren syndrome and developed strategies for modifier discovery in this rare disease population. Approaches include extreme phenotyping and nonsynonymous variant prioritization, followed by gene set enrichment and pathway‐level association tests. We next used GTEx v8 and proteomic data sets to verify expression of candidate modifiers in relevant tissues. Finally, we evaluated overlap between the genes/pathways identified here and those ascertained through larger aortic disease/trait genome‐wide association studies. We show that SVAS severity in Williams–Beuren syndrome is associated with increased frequency of common and rarer variants in matrisome and immune pathways. Two implicated matrisome genes (ACAN and LTBP4) were uniquely expressed in the aorta. Many genes in the identified pathways were previously reported in genome‐wide association studies for aneurysm, bicuspid aortic valve, or aortic size. Conclusions Smaller sample sizes in rare disease studies necessitate new approaches to detect modifiers. Our strategies identified variation in matrisome and immune pathways that are associated with SVAS severity. These findings suggest that, like other aortopathies, SVAS may be influenced by the balance of synthesis and degradation of matrisome proteins. Leveraging multiomic data and results from larger aorta‐focused genome‐wide association studies may accelerate modifier discovery for rare aortopathies like SVAS.

ObjectiveTo assess whether case finding for depression among people aged 65 and above improves mental health.DesignOpportunistic evaluation using a regression discontinuity analysis with data from a randomised controlled trial.SettingThe REFORM trial, a falls prevention study that recruited patients from NHS podiatry clinics.Participants1010 community-dwelling adults over the age of 65 with at least one risk factor for falling (recent previous fall or fear of falling).InterventionLetter sent to patient's General Practitioner if they scored 10 points or above on the 15-item Geriatric Depression Scale (GDS-15) informing them of the patient's risk of depression.Main outcome measureGDS-15 score six months after initial completion of GDS-15.Results895 (88.6%) of the 1010 participants randomised into REFORM had a valid baseline and six-month GDS-15 score and were included in this study. The mean GDS-15 baseline score was 3.5 (SD 3.0, median 3.0, range 0-15); 639 (71.4%) scored 0-4, 204 (22.8%) scored 5-9 indicating mild depression, and 52 (5.8%) scored 10 or higher indicating severe depression. At six months follow-up, those scoring 10 points or higher at baseline had, on average, a reduction of 1.08 points on the GDS-15 scale (95% confidence interval -1.83 to -0.33, p = 0.005) compared to those scoring less than 10, using the simplest linear regression model.ConclusionCase finding of depression in podiatry patients based on a GDS-15 score of 10 or more followed by a letter to their General Practitioner significantly reduced depression severity. Whether this applies to all older patients in primary care is unknown. Further research is required to confirm these findings. Regression discontinuity analyses could be prespecified and embedded within other existing research studies.

IntroductionThis qualitative study explores older adults' attitudes towards hearing difficulties, health-seeking behaviour and hearing aid use in Samutprakarn, Thailand.MethodThree focus groups (n=25), with adults aged 60-88 years, were conducted within a residential complex for older adults. Qualitative data analysis, employing a phenomenological approach was completed.ResultsFour themes are presented: (1) Perception of hearing difficulties, (2) Experience of receiving care, (3) Attitudes towards wearing hearing aids, and (4) Raising awareness of hearing difficulties in older adults. Findings indicate that Thai older adults may not be aware or accepting of their hearing difficulties, due to the stigma associated hearing loss, older age, and disability. The consequential impact of these unacknowledged issues manifest in communication challenges and the adoption of avoidance behaviours across diverse situational contexts.ConclusionThis study enhances our understanding of how Thai older adults perceive hearing problems and ear care. Findings underscore the potential pivotal role of familial and social networks in mitigating barriers associated with hearing difficulties among older adults in Thailand. These insights can raise awareness and inform effective management for older adults and their families. Additionally, the findings could guide healthcare providers, researchers, and policy makers, fostering improved care for this demographic.

This paper explores Itinerant Medicine Sellers’ (IMSs) operations at loading bays within bus terminals in the Kumasi metropolis. The paper examines how the sellers negotiated access into the loading bays, how they marketed their medicines, where they sourced their medicines from, and the challenges they faced. An exploratory qualitative survey design was adopted for the study. Through convenience sampling, 18 IMSs operating within the bus terminals in the Kumasi metropolis participated in this study. In-depth interviews were conducted, audio-recorded and transcribed. The transcripts were thematically analysed. The study found that these hawkers negotiated access to the loading bays through multiple informal gatekeepers and employed direct customer engagement in marketing their medicines. It was further revealed that the IMSs sourced their medicines from both formal and informal sources for different reasons, such as affordability and informality of medicines acquisition. The participants operated outside government-prescribed regulations and faced challenges of low capital and sales revenue, poor reception by prospective clients, and government clampdown. The study concludes that medicine hawking is an illegal livelihood strategy and a public health concern. As a phenomenon outside government’s policy guidelines, it is recommended that government intensifies its clampdown activities on these hawkers and engage in public health education on the negative implications of accessing medicines from these IMSs.

Abstract Background Investigations conducted among healthcare providers to assess their knowledge and perceptions towards the integration of anti-retroviral therapy (ART) related services in Sub-Saharan Africa are limited. This study explored the knowledge and perceptions of primary healthcare providers towards the integration of ART management services at departmental levels in health facilities in Lira district. Methods We conducted a descriptive cross-sectional survey that employed qualitative methods of data collection in four selected health facilities in Lira district between January and February 2022. The study involved in-depth interviews with key informants and focus group discussions. The study population consisted exclusively of primary healthcare providers; however, those who were not full-time employees of the participating health facilities were excluded. We used thematic content analysis. Results A significant proportion of staff (especially those who are not directly involved in ART) still lack full knowledge of ART services integration. There was generally a positive perception, with some suggesting ART integration can minimize stigma and discrimination. The potential barriers to integration included limited knowledge and skills for providing comprehensive ART services, insufficient staffing and space, funding gaps, and inadequate drug supplies, coupled with increased workload due to enlarged clientele. Conclusion Whereas healthcare workers are generally knowledgeable about ART integration, but their knowledge was limited to partial integration. The participants had a basic understanding of ART services being provided by different health facilities. Furthermore, participants viewed integration as critical, but it should be implemented in conjunction with ART management training. Given that respondents reported a lack of infrastructure, increased workload, and understaffing, additional investments in staff recruitment, motivation through training and incentives, and other means are needed if ART integration is to be implemented.

Abstract Introduction COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. Methods Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. Results Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 – 1.39; targeted therapy OR 1.89, 95% CI 0.64 – 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 – 2.35). Conclusions Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.

Abstract Background Difficulty in transportation to access skilled providers has been cited repeatedly as a major barrier to utilization of emergency obstetric care in Nigeria. Objective The objective of this paper is to describe the design, implementation, and outcomes of a mobile phone technology aimed at rapidly reaching rural Nigerian women who experience pregnancy complications with emergency transportation and access to providers. Method The project was implemented in 20 communities in two predominantly rural Local Government Areas (LGAs) of Edo State, in southern Nigeria, as part of a larger implementation project aimed at improving the access of rural women to skilled pregnancy care. The digital health innovation named Text4Life, allowed women to send a brief message from their mobile phone to a server linked to Primary Health Care (PHC) facilities and to access pre-registered transport owners. Pregnant women were registered and taught to text short messages to a server from their mobile phones or those of a friend or relative when they experience complications. Results Over 18 months, 56 women out of 1620 registered women (3.5%) texted the server requesting emergency transportation. Of this number, 51 were successfully transported to the PHC facilities, 46 were successfully treated at the PHC, and five were referred to higher-level care facilities. No maternal deaths occurred during the period, while four perinatal deaths were recorded. Conclusion We conclude that a rapid short message sent from a mobile phone to a central server and connected to transport providers and health facility managers is effective in increasing the access of pregnant women to skilled emergency obstetric services in rural Nigeria.

An animal’s responses to environmental cues are critical for its reproductive program. Thus, a mechanism that allows the animal to sense and adjust to its environment should make for a more efficient reproductive physiology. Here, we demonstrate that in Caenorhabditis elegans specific sensory neurons influence onset of oogenesis through insulin signaling in response to food-derived cues. The chemosensory neurons ASJ modulate oogenesis onset through the insulin-like peptide (ILP) INS-6. In contrast, other sensory neurons, the olfactory neurons AWA, regulate food type-dependent differences in C. elegans fertilization rates, but not onset of oogenesis. AWA modulates fertilization rates at least partly in parallel to insulin receptor signaling, since the insulin receptor DAF-2 regulates fertilization independently of food type, which requires ILPs other than INS-6. Together our findings suggest that optimal reproduction requires the integration of diverse food-derived inputs through multiple neuronal signals acting on the C. elegans germline.

Abstract Cardiac electrophysiology mapping and ablation are widely used to treat heart rhythm disorders such as atrial fibrillation (AF) and ventricular tachycardia (VT). Here, we describe an approach for rapid production of three dimensional (3D)‐printed mapping devices derived from magnetic resonance imaging. The mapping devices are equipped with flexible electronic arrays that are shaped to match the epicardial contours of the atria and ventricle and allow for epicardial electrical mapping procedures. We validate that these flexible arrays provide high‐resolution mapping of epicardial signals in vivo using porcine models of AF and myocardial infarction. Specifically, global coverage of the epicardial surface allows for mapping and ablation of myocardial substrate and the capture of premature ventricular complexes with precise spatial–temporal resolution. We further show, as proof‐of‐concept, the localization of sites of VT by means of beat‐to‐beat whole‐chamber ventricular mapping of ex vivo Langendorff‐perfused human hearts.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32–1.67]); Black patients (aOR 1.74; 95 CI 1.24–2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70–6.79) and Other (aOR 2.97; 95 CI 1.71–5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83–12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63–3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20–2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66–3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89–22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.

Background & Aim: Breach awareness in relation to types, mitigation, and reporting should be a routine part of infection prevention training. Understanding breaches can reduce the risk of disease transmission to staff and communities when contextualized to the infectious disease, environment, and situation. At a large-scale Australian COVID-19 quarantine facility, this study examined the core personal protective equipment and infection prevention breaches new quarantine workers identified during their site orientation to inform future breach training. Methods & Materials: Through the application of a qualitative approach, the project implemented a descriptive thematic analysis to identify the different types of breaches staff presented. An additional summative content analysis method was applied to determine if the breaches staff identified were breaching and if the risk level staff allocated to the breach was mapped to the risk of disease transmission. Data were collected from 30 orientation sessions and included 603 breach risk responses for analysis.Results: There were five core breach areas identified: donning and doffing of personal protective equipment, failure of personal protective equipment or lack of equipment, environmental factors, staff behaviors, and resident behaviors. The breach allocations by staff demonstrated knowledge deficits across health and non-health staff in disease transmission, particularly in the actual level of risk for transmission. Conclusion: Breaches awareness in relation to types, mitigation, and reporting should be a routine part of infection prevention training. The five areas of breaches present an adaptable foundation to base infection prevention breach training for any health facility. When contextualized to the communicable disease, environment, and situation, understanding breaches can reduce the risk of disease transmission to staff and communities.

Personal life and professional life are two significant grounds that may affect one another. A profession can distract personal life while personal life can hinder professional life. Both conflicts may lead to unfavorable outcomes in personal and professional life. The study focused on the experiences of the faculty from Polytechnic University of the Philippines Bataan Branch during the implementation of an alternative work scheme because of quarantine implementation and a series of lockdowns. Forty-six (46) or 70% faculty members participated in the study regardless of their status. It was conducted during the Academic Year 2020 to 2021, second Semester. The study revealed that time management was found out to have a positive correlation to availability, preparation, and work environment at a low extent but negatively correlated to the family conflict to a moderate extent. On the other hand, time management has a positive correlation to the overall home-related factors to a moderate extent. Instructional materials were found out to have a positive correlation to availability, work environment, internet connection, and overall home-related factors to a moderate extent. Class monitoring was positively correlated to availability, work environment, and to the internet connection to a low extent but negatively correlated to a low extent with family conflict. On the contrary, class monitoring has a positive correlation to a moderate extent to overall home-related factors. Overall work-related factors were found out to be positively correlated to availability, preparation, work environment, internet connection, and overall home-related factors to a moderate extent.

Abstract Plant biostimulants include beneficial fungi and bacteria, and are often applied to foliage to improve crop growth, yield, and/or crop quality. Crop improvements due to biostimulant addition may be modest; therefore, solo applications may not be economical or climate smart. However, biostimulants combined with other postemergence treatments, such as herbicides, may provide an alternative application method, if mixtures do not harm the living organism(s). The growth of Bradyrhizobium japonicum, as a biostimulant surrogate, was assessed in solutions of glyphosate [N‐(phosphonomethyl)glycine] and dicamba (3,6‐dichloro‐2‐methoxybenzoic acid), with and without common spray additives (ammonium sulfate [AMS] and nonionic surfactant) in laboratory studies over 72 h. Solution turbidity, using optical density as a surrogate of bacterial growth, was measured at 600 nm at 24, 48, and 72 h after inoculation, and colony forming units (CFUs) per milliliter were estimated. Growth was not detected in either the glyphosate or AMS solutions, most likely due to the low pH and high electrical conductivity of the solutions, respectively. When herbicides were mixed with a nonionic surfactant, CFUs per milliliter were about 25% greater than the positive control. These data suggest that mixing bacteria with postemergence herbicide + surfactants/additives combinations can hinder or maintain growth when preparing for agrochemical applications. Biostimulant type and the agrichemical combination(s) should be evaluated prior to tank mixing to determine if detrimental interactions occur. After application, an evaluation of the effectiveness of the biostimulant to the crop and efficacy of the agrichemical to the target organism should be conducted.

Background: A screening tool to predict response to cardiac resynchronization therapy (CRT) could improve patient selection and outcomes. Objective: The purpose of this study was to investigate the feasibility and safety of noninvasive CRT via transcutaneous ultrasonic left ventricular (LV) pacing applied as a screening test before CRT implants. Methods: P-wave–triggered ultrasound stimuli were delivered during bolus dosing of an echocardiographic contrast agent to simulate CRT noninvasively. Ultrasound pacing was delivered at a variety of LV locations with a range of atrioventricular delays to achieve fusion with intrinsic ventricular activation. Three-dimensional cardiac activation maps were acquired via the Medtronic CardioInsight 252-electrode mapping vest during baseline, ultrasound pacing, and after CRT implantation. A separate control group received only the CRT implants. Results: Ultrasound pacing was achieved in 10 patients with a mean of 81.2 ± 50.8 ultrasound paced beats per patient and up to 20 consecutive beats of ultrasound pacing. QRS width at baseline (168.2 ± 17.8 ms) decreased significantly to 117.3 ± 21.5 ms (P

Aims: Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set. Methods: A total of 11 databases were searched. A subset of studies published between 1 October 2020 and 1 January 2011 from a larger review mapping research on limb reconstruction and limb amputation for the management of lower limb COM were eligible. All outcomes were extracted and recorded verbatim. Outcomes were grouped and categorized as per the revised Williamson and Clarke taxonomy. Results: A total of 3,303 records were screened, of which 99 studies were included. Most studies were case series (77/99; 78%) and assessed one method of reconstruction (68/99; 69%). A total of 511 outcomes were reported, which were grouped into 58 distinct outcomes. Overall, 143/511 of all outcomes (28%) were provided with a clear, in-text definition, and 231 outcomes (45%) had details reported of how and when they were measured. The most commonly reported outcome was ‘recurrence of osteomyelitis’ (62; 12%). The single-most patient-reported outcome measure was ‘pain’. Conclusion: This study has highlighted significant inconsistencies in the defining, reporting, and measuring of outcomes across studies investigating surgical management for chronic osteomyelitis of the lower limb in adults. Future studies should clearly report complete details of how outcomes are defined and measured, including timing. The development of a standardized core outcome set would be of significant benefit in order to allow evidence synthesis and comparison across studies. Cite this article: Bone Jt Open 2023;4(3):146–157.

Abstract Background Since the onset of the recent COVID-19 pandemic, there have been growing concerns regarding multisystem inflammatory syndrome in children (MIS-C). This study aims to describe the clinico-epidemiological profile and challenges in management of MIS-C in low-middle income countries by highlighting the Kenyan experience. Methods A retrospective study at the Aga Khan University Hospital Nairobi, Avenue Hospital Kisumu and Kapsabet County Referral Hospital was undertaken to identify cases of MIS-C. A detailed chart review using the World Health Organization (WHO) data collection tool was adapted to incorporate information on socio-demographic details and treatment regimens. Findings Twenty children with MIS-C were identified across the three facilities between August 1st 2020 and August 31st 2021. Seventy percent of the children were male (14 of 20). COVID-19 PCR testing was done for five children and only one was positive. The commonest clinical symptoms were fever (90%), tachycardia (80%), prolonged capillary refill (80%), oral mucosal changes (65%) and peripheral cutaneous inflammation (50%). Four children required admission into the critical care unit for ventilation support and inotropic support. Cardiac evaluation was available for six patients four of whom had myocardial dysfunction, three had valvulitis and one had pericarditis. Immunoglobulin therapy was availed to two children and systemic steroids provided for three children. There were no documented mortalities. Interpretation We describe the first case series of MIS-C in East and Central Africa. Majority of suspected cases of MIS-C did not have access to timely COVID-19 testing and other appropriate evaluations which highlights the iniquity in access to diagnostics and treatment.

The current earthquake monitoring system uses a seismometer that can capture seismic vibrations very well but is expensive, heavy, and difficult to launch. Therefore, earthquake monitoring stations can only be launched in a few places in small numbers. This study aims to implement a Wireless Sensor Network (WSN) system for earthquake monitoring. The WSN system has advantages in cost, size, and ease of launch, so it is very appropriate to be used for this purpose. An earthquake detection sensor system has been designed in this study using a vibration sensor and a piezoelectric sensor. When an earthquake occurs, the resulting shock will trigger the vibration sensor and activate the sensor node. The shock data is then captured by the piezo sensor and processed by the microcontroller using Fast Fourier Transform (FFT) to determine the frequency value of the shock. The data is then sent to a gateway via a sensor network and uploaded to the Cayenne monitoring website. Operators can then view the data on the website. Three sensor nodes are implemented in this study. The test is done by placing those sensor nodes together in random positions. A shock is then given to the three sensor nodes, and the resulting data is then observed. The results show that the three sensors can detect, retrieve, process, and send shock data to the Cayenne monitoring website.

Abstract The internal mechanisms responsible for modulating physiological condition, particularly those performed by the gut microbiome (GMB), remain under-explored in wildlife. However, as latitudinal and seasonal shifts in resource availability occur, the myriad micro-ecosystem services facilitated by the GMB may be especially important to wildlife health and resilience. Here, we use brown bears (Ursus arctos) as an ecological model to quantify the relationship between wildlife body condition metrics that are commonly used to assess individual and population-level health and GMB community composition and structure. To achieve these aims, we subsampled brown bear fecal samples collected during United States National Park Service research activities at three National Parks and Preserves (Katmai, Lake Clark, and Gates of the Arctic) and extracted microbial DNA for 16S rRNA amplicon sequencing and microbial taxonomic classification. We analyzed GMB communities using alpha diversity indices, subsequently using Spearman’s correlation analysis to examine relationships between alpha diversity and brown bear health metrics. We found no differences in GMB composition among bears with differing body conditions, nor any correlations between alpha diversity and body condition. Our results indicate that GMB composition reflects diverse foraging strategies while allowing brown bears to achieve similar body condition outcomes.