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Abstract Background Acoustic telemetry has become a fundamental tool to monitor the movement of aquatic species. Advances in technology, in particular the development of batteries with lives of > 10 years, have increased our ability to track the long-term movement patterns of many species. However, logistics and financial constraints often dictate the locations and deployment duration of acoustic receivers. Consequently, there is often a compromise between optimal array design and affordability. Such constraints can hinder the ability to track marine animals over large spatial and temporal scales. Continental-scale receiver networks have increased the ability to study large-scale movements, but significant gaps in coverage often remain. Methods Since 2007, the Integrated Marine Observing System’s Animal Tracking Facility (IMOS ATF) has maintained permanent receiver installations on the eastern Australian seaboard. In this study, we present the recent enhancement of the IMOS ATF acoustic tracking infrastructure in Queensland to collect data on large-scale movements of marine species in the northeast extent of the national array. Securing a relatively small initial investment for expanding receiver deployment and tagging activities in Queensland served as a catalyst, bringing together a diverse group of stakeholders (research institutes, universities, government departments, port corporations, industries, Indigenous ranger groups and tourism operators) to create an extensive collaborative network that could sustain the extended receiver coverage into the future. To fill gaps between existing installations and maximise the monitoring footprint, the new initiative has an atypical design, deploying many single receivers spread across 2,100 km of Queensland waters. Results The approach revealed previously unknown broad-scale movements for some species and highlights that clusters of receivers are not always required to enhance data collection. However, array designs using predominantly single receiver deployments are more vulnerable to data gaps when receivers are lost or fail, and therefore “redundancy” is a critical consideration when designing this type of array. Conclusion Initial results suggest that our array enhancement, if sustained over many years, will uncover a range of previously unknown movements that will assist in addressing ecological, fisheries, and conservation questions for multiple species.

Background: The benefit of prophylactic whole pelvis radiation therapy (WPRT) in prostate cancer has been debated for decades, with evidence based mainly on conventional fractionation targeting pelvic nodes. Aim: This retrospective cohort study aimed to explore the impact of adding moderately hypofractionated pelvic radiotherapy to prostate-only irradiation (PORT) on prognosis, toxicity, and quality of life in real-world settings. Materials and methods: Patients with high-risk and conventionally staged prostate cancer (cT1-3N0M0) treated with moderately hypofractionated WPRT or PORT, using external beam radiotherapy alone or combined with high-dose-rate brachytherapy, at Örebro University Hospital between 2008 and 2021 were identified. Biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier method and Cox proportional hazards. Toxicity and quality of life measures were also analysed. Results: Among 516 patients (227 PORT, 289 WPRT), 5-year BFFS rates were 77 % (PORT) and 74 % (WPRT), adjusted HR=1.50 (95 % CI=0.88–2.55). No significant differences were found in MFS, PCSS, or OS in main analyses. WPRT was associated with a higher risk of acute grade ≥ 2 and 3 genitourinary toxicities whereas no differences in late toxicities or quality of life between PORT and WPRT were observed. Conclusion: We found no significant differences in oncological outcomes or quality of life when comparing moderately hypofractionated PORT to WPRT. Some differences in toxicity patterns were observed. Despite caveats related to study design, our findings support the need for further research on WPRT’s impact on treatment-related and patient-reported outcomes.

Background and purpose: In many clinics, positron-emission tomography is unavailable and clinician time extremely limited. Here we describe a deep-learning model for autocontouring gross disease for patients undergoing palliative radiotherapy for primary lung lesions and/or hilar/mediastinal nodal disease, based only on computed tomography (CT) images. Materials and methods: An autocontouring model (nnU-Net) was trained to contour gross disease in 379 cases (352 training, 27 test); 11 further test cases from an external centre were also included. Anchor-point-based post-processing was applied to remove extraneous autocontoured regions. The autocontours were evaluated quantitatively in terms of volume similarity (Dice similarity coefficient [DSC], surface Dice coefficient, 95th percentile Hausdorff distance [HD95], and mean surface distance), and scored for usability by two consultant oncologists. The magnitude of treatment margin needed to account for geometric discrepancies was also assessed. Results: The anchor point process successfully removed all erroneous regions from the autocontoured disease, and identified two cases to be excluded from further analysis due to ‘missed’ disease. The average DSC and HD95 were 0.8 ± 0.1 and 10.5 ± 7.3 mm, respectively. A 10-mm uniform margin-distance applied to the autocontoured region was found to yield “full coverage” (sensitivity > 0.99) of the clinical contour for 64 % of cases. Ninety-seven percent of evaluated autocontours were scored by both clinicians as requiring no or minor edits. Conclusions: Our autocontouring model was shown to produce clinically usable disease outlines, based on CT alone, for approximately two-thirds of patients undergoing lung radiotherapy. Further work is necessary to improve this before clinical implementation.

Accurately predicting grape yield in vineyards is essential for strategic decision-making in the wine industry. Current methods are labour-intensive, costly, and lack spatial coverage, reducing accuracy and cost-efficiency. Efforts to automate and enhance yield estimation focus on scaling fruit weight assessments. Machine learning, particularly deep learning, shows promise in improving accuracy through automatic feature extraction and hierarchical representation. However, most of these methods have been developed for analyses at a particular time point and solutions able to consider temporal information captured across sequential frames are currently poorly developed. This paper addresses this gap by introducing a system for yield estimation, utilising publicly available data repositories, such as Embrapa WGISD, alongside an in-house dataset collected by a Blackmagic camera at the pre-harvest stage. We introduce a system that utilises bunch weight regression to estimate grape yield. Bunch weight estimates are obtained by summing samples randomly drawn from the grape bunch weight distribution through empirical calibration. Grapevine bunches are identified and segmented using Mask R-CNN with Swin Transformer, and a SiamFC-based tracking mechanism is employed to estimate the number of unique bunches per panel or row. The number of berries for each tracked bunch is determined using a density approach known as multitask point supervision. In our experiments, we demonstrate the effectiveness of the proposed system for yield estimation, achieving harvested weight errors of less than 5% in two of the three vineyard panels. Larger harvest weight errors (around 15%) were observed due to inaccuracies in tracking certain bunches caused by dense concentration of bunches in one panel. However, these errors should be contrasted with the current practice error of up to 30%, highlighting the potential of machine vision for hands-off yield estimation at scale.

Aims To compare receipt of acute cardiac care in people with versus without severe mental illness (SMI) and investigate the impact of the COVID-19 pandemic on any differences in care. We hypothesised that, compared with those without SMI, patients with an SMI are less likely to receive guideline recommended acute cardiac care and that disparities worsened as a result of the pandemic. Methods We conducted a cohort study using data from the CVD-COVID-UK resource, which links electronic health data from multiple sources. Our cohort included 95,125 adults with a non-ST-elevation MI (NSTEMI) recorded in the Myocardial Infarction National Audit Programme (MINAP) dataset between 1 November 2019 and 31 March 2022. We defined SMI as schizophrenia, schizoaffective disorders or bipolar disorder (BD), ascertained through recorded diagnosis in primary care or hospital admission records. We examined receipt of cardiac care standards for NSTEMI, including: admission to a cardiac ward; angiogram eligibility; receipt of angiogram (in those eligible); angiogram within 72 hours; secondary prevention medication prescribing at discharge, and arrangement of post-discharge cardiac rehabilitation. We used logistic regression to obtain odds ratios (ORs) for the association between SMI and receipt of each care indicator, adjusting for age, sex and time period. We tested for an interaction between SMI and time period in order to determine if any disparities had changed since the start of the COVID-19 pandemic. Results Within our cohort, 620 patients (0.6%) had schizophrenia and 575 (0.6%) had BD. Compared with people without SMI and after adjusting for age, sex and period, patients with an SMI were less likely to receive each of the cardiac care standards. For example, compared with those without SMI, those with SMI were less likely to: be admitted to a cardiac ward (schizophrenia: OR 0.72, 95% CI 0.61–0.85; BD: 0.74, 95% CI 0.63–0.88); be eligible for an angiogram (schizophrenia: 0.37, 95% CI 0.29–0.47; BD: 0.52, 95% CI 0.40–0.68); receive an angiogram (schizophrenia: 0.22, 95% CI 0.18–0.28; BD: 0.51, 95% CI 0.39–0.66); and receive an angiogram within 72 hours (schizophrenia: 0.71, 95% CI 0.56–0.90); BD: 0.80, 95% CI 0.64–1.00). We generally found no evidence that disparities had changed since the start of the COVID-19 pandemic. Conclusion We identified marked SMI disparities in receipt of acute cardiac care among people treated in hospital for a NSTEMI. Further research should seek to identify reasons for, and inform interventions to, address these disparities.

Aims To understand the challenges and barriers experienced by health-care professionals (HCPs) in providing acute cardiac care to patients with severe mental illness (SMI) (schizophrenia, bipolar disorder or severe depression) admitted to hospital following a myocardial infarction (MI). Methods Semi-structured 1:1 videocall interviews with 12 HCPs in two central-Scotland Health Boards involved in delivering pre-/hospital acute care for a MI (paramedics, cardiology/A&E nurses, cardiology/A&E doctors). Interviewee recruitment was via clinical and research networks and newsletters e.g. the Scottish Ambulance Service, the Royal College of Nursing and Royal College of Physicians and through professional connections. Interviews were audio-recorded, transcribed verbatim and analysed thematically drawing on Braun & Clarke and using NVivo software. Results HCPs identified a number of challenges/barriers to providing optimal post-MI acute cardiac care to patients with a SMI across 3 key themes: patient-related; practitioner-related and system/environment-related. Core patient-related challenges/barriers included: diminished patient history capacities especially relating to chronology; the time-consuming nature of effective HCP-patient communication and engagement; medication and intervention concordance concerns and challenging patient behaviour including physical and verbal aggression or severe distress. Practitioner-related challenges/barriers were: fears of appropriately managing patient behaviour; stigma towards patients with a SMI (putatively arising from knowledge deficits or generational/age-related effects); staff burnout due to length of service and pressures from extreme workloads. Systemic issues included insufficient staffing precluding the additional time required for effective communication and the distressing nature of hospital environments for patients with a SMI. Side rooms were not routinely available even though these were identified as improving the environment for some patients. A core systemic finding, cited by all interviewees, was the lack of adequate training provision on caring for patients with a SMI. Additional system-level findings were degrees of challenges accessing input from the hospital psychiatric team especially outwith standard hours and problems obtaining rarer psychiatric medications potentially impacting patients’ mental health stability. Positive findings included that HCPs are generally enthusiastic about providing high quality care to this patient group and to seek help with this. Some HCPs indicated that caring for mentally stable patients with a SMI does not differ from the general population. Conclusion Although HCPs aspired to providing optimal acute cardiac care for this patient group, patient-level, professional and systemic barriers often make this challenging. A key area for improvement is enhancing staff training in caring for patients with SMI, ideally delivered in-person.

Abstract Background Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. Methods Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. Results The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. Conclusion UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

Abstract Applying deep learning to images of cropping systems provides new knowledge and insights in research and commercial applications. Semantic segmentation or pixel-wise classification, of RGB images acquired at the ground level, into vegetation and background is a critical step in the estimation of several canopy traits. Current state of the art methodologies based on convolutional neural networks (CNNs) are trained on datasets acquired under controlled or indoor environments. These models are unable to generalize to real-world images and hence need to be fine-tuned using new labelled datasets. This motivated the creation of the VegAnn - Vegetation Annotation - dataset, a collection of 3775 multi-crop RGB images acquired for different phenological stages using different systems and platforms in diverse illumination conditions. We anticipate that VegAnn will help improving segmentation algorithm performances, facilitate benchmarking and promote large-scale crop vegetation segmentation research.

Abstract Background Widening participation (WP) for underrepresented students through six-year gateway courses helps to widen the demographic representation of doctors in the UK. ‘Most students from gateway courses graduate, even though many enter with lower grades than standard entry medicine students.’ This study aims to compare the graduate outcomes of gateway and SEM cohorts from the same universities. Methods Data from 2007–13 from the UK Medical Education Database (UKMED) were available for graduates of gateway and SEM courses at three UK medical schools. Outcome measures were passing an entry exam on the first attempt, Annual Review of Competency Progression (ARCP) outcome and being offered a level one training position from the first application. The univariate analysis compared the two groups. Logistic regressions, predicting outcomes by course type, controlled for attainment on completion of medical school. Results Four thousand four hundred forty-five doctors were included in the analysis. There was no difference found in the ARCP outcome between gateway and SEM graduates. Gateway graduates were less likely to pass their first attempt at any membership exam than graduates of SEM courses (39% vs 63%). Gateway graduates were less likely to be offered a level 1 training position on their first application (75% vs 82%). Graduates of gateway courses were more likely to apply to General Practitioner (GP) training programmes than SEM graduates (56% vs 39%). Conclusions Gateway courses increase the diversity of backgrounds represented within the profession and importantly the number of applications to GP training. However, differences in cohort performance are shown to continue to exist in the postgraduate arena and further research is required to ascertain the reasons for this.

Axial resolution is one of the most important characteristics of a microscope. In all microscopes, a high axial resolution is desired in order to discriminate information efficiently along the longitudinal direction. However, when studying thick samples that do not contain laterally overlapping information, a low axial resolution is desirable, as information from multiple planes can be recorded simultaneously from a single camera shot instead of plane-by-plane mechanical refocusing. In this study, we increased the focal depth of an infrared microscope non-invasively by introducing a binary axicon fabricated on a barium fluoride substrate close to the sample. Preliminary results of imaging the thick and sparse silk fibers showed an improved focal depth with a slight decrease in lateral resolution and an increase in background noise.

Abstract N,N'‐dimethyl‐4,4'bipyridinium dichloride (Paraquat) is a potent herbicide used widely in agriculture. We report the effects of an ingestion of paraquat by a 28 year old male with cystic fibrosis and the diagnostic and management challenges this posed in both the acute and longer term setting. We describe the effects of direct paraquat toxicity on the lung tissue secondary to aspiration and review the long‐term sequelae of paraquat, namely osteonecrosis. Our case is the first to describe osteonecrosis of the knee in the context of paraquat toxicity. Survival following ingestion remains poor with a high associated mortality. However, timely treatment with NAC and immunosuppression may impact on survival. In those patients who do survive the acute phase post ingestion, follow‐up over years may be required to detect the long‐term effects of paraquat on bone health.

AbstractCarbon farming presents an opportunity for the land sector to generate income and transition to more sustainable land management practices. In Australia, establishing a carbon project and earning carbon credits is complex, with project proponents needing to satisfy eligibility requirements and adhere to rigorous measurement, verification, and reporting protocols of approved methods. To address these challenges, a human centered design (HCD) approach was used to deliver a digital solution, serving landowners’ needs related to method discovery and reconfiguring how the methodological and scientific complexity of abatement potentials was delivered. The solution, called LOOC-C (pronounced “Look-see”), supports the discovery of abatement methods that are available for a given land area and provides an initial estimate of the potential quantum of carbon sequestered/emitted and the nature of co-benefits associated with each eligible method. Reporting on LOOC-C development and its observed impact demonstrates the role that human centered digital tools have in promoting land management actions that are both sustainable and reasonable to undertake. It equally demonstrates the power of integrating environmental market and user requirements with a robust design methodology. With similar opportunities in environmental markets globally, additional applications of an HCD approach are proposed.

Abstract Mungbean (Vigna radiata (L.) R. Wilczek var. radiata) is a significant food and cash crop grown in tropical and subtropical regions. Mungbean production and consumer demand have increased substantially over the last two decades, owing to its agronomic, nutritional and economic benefits. Despite increased breeding efforts and the expansion of mungbean production in various agro‐climatic regions, further production is hindered by low yield and variability, which is partly attributed to the impacts of abiotic stress. Abiotic stress impacts on the physiology, morphology and reproductive ability of mungbean which influences yield. Exposure to abiotic stresses at the reproductive stage is considered the most critical for yield production. In this review, we evaluate how abiotic stress impacts mungbean growth and productivity when occurring during the reproductive stage and traits that may confer adaptation. We present the limitations of current research including limited number of genotypes, lack of field experiments and detailed experimental information. We highlight the opportunities to exploit new tools and technologies, such as high‐throughput phenotyping platforms, gene editing, and genomic selection, to accelerate breeding efforts to develop more resilient mungbean cultivars for today and tomorrow.

Abstract Introduction Personalized disease management informed by quantitative risk prediction has the potential to improve patient care and outcomes. The integration of risk prediction into clinical workflow should be informed by the experiences and preferences of stakeholders, and the impact of such integration should be evaluated in prospective comparative studies. The objectives of the IMplementing Predictive Analytics towards efficient chronic obstructive pulmonary disease (COPD) treatments (IMPACT) study are to integrate an exacerbation risk prediction tool into routine care and to determine its impact on prescription appropriateness (primary outcome), medication adherence, quality of life, exacerbation rates, and sex and gender disparities in COPD care (secondary outcomes). Methods IMPACT will be conducted in two phases. Phase 1 will include the systematic and user-centered development of two decision support tools: (1) a decision tool for pulmonologists called the ACCEPT decision intervention (ADI), which combines risk prediction from the previously developed Acute COPD Exacerbation Prediction Tool with treatment algorithms recommended by the Canadian Thoracic Society’s COPD pharmacotherapy guidelines, and (2) an information pamphlet for COPD patients (patient tool), tailored to their prescribed medication, clinical needs, and lung function. In phase 2, we will conduct a stepped-wedge cluster randomized controlled trial in two outpatient respiratory clinics to evaluate the impact of the decision support tools on quality of care and patient outcomes. Clusters will be practicing pulmonologists (n ≥ 24), who will progressively switch to the intervention over 18 months. At the end of the study, a qualitative process evaluation will be carried out to determine the barriers and enablers of uptake of the tools. Discussion The IMPACT study coincides with a planned harmonization of electronic health record systems across tertiary care centers in British Columbia, Canada. The harmonization of these systems combined with IMPACT’s implementation-oriented design and partnership with stakeholders will facilitate integration of the tools into routine care, if the results of the proposed study reveal positive association with improvement in the process and outcomes of clinical care. The process evaluation at the end of the trial will inform subsequent design iterations before largescale implementation. Trial registration NCT05309356.

Abstract Introduction Pulmonary rehabilitation is recommended for people with bronchiectasis. Various education topics are included in these programmes, but the content is largely guided by the needs of people with other respiratory conditions. Objectives With the education topics applicable to people with bronchiectasis unclear, we aimed to explore the perspective of adults with this condition on relevant educational topics in a pulmonary rehabilitation context. Methods Participants from the Australian Bronchiectasis Registry were invited to undertake a semi‐structured interview. Interview transcripts were coded independently, with themes established by consensus (two researchers). Results Twenty‐one people participated. The major themes were greater clarity on the underlying cause of bronchiectasis and prognosis. Most sought knowledge about self‐management strategies and treatments to address extra‐pulmonary symptoms. Participants requested more information on physiotherapy options and the role of exercise and physical activity outside of pulmonary rehabilitation. Preferences were mixed for the education delivery model. Conclusions We have identified unmet educational topics of interest for people with bronchiectasis. Our study provides a framework for education topics desired by adults with bronchiectasis within a pulmonary rehabilitation setting. The topics identified will guide development of an education curriculum for pulmonary rehabilitation that is more fit‐for‐purpose for people with bronchiectasis.

Emerging applications of optical technologies are driving the development of miniaturised light sources, which in turn require the fabrication of matching micro-optical elements with sub-1 mm cross-sections and high optical quality. This is particularly challenging for spatially constrained biomedical applications where reduced dimensionality is required, such as endoscopy, optogenetics, or optical implants. Planarisation of a lens by the Fresnel lens approach was adapted for a conical lens (axicon) and was made by direct femtosecond 780 nm/100 fs laser writing in the SZ2080™ polymer with a photo-initiator. Optical characterisation of the positive and negative fraxicons is presented. Numerical modelling of fraxicon optical performance under illumination by incoherent and spatially extended light sources is compared with the ideal case of plane-wave illumination. Considering the potential for rapid replication in soft polymers and resists, this approach holds great promise for the most demanding technological applications.

Abstract Background The rapid course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic calls for fast implementation of clinical trials to assess the effects of new treatment and prophylactic interventions. Building trial platforms embedded in existing data infrastructures is an ideal way to address such questions within well-defined subpopulations. Methods We developed a trial platform building on the infrastructure of two established national cohort studies: the Swiss human immunodeficiency virus (HIV) Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS). In a pilot trial, termed Corona VaccinE tRiAL pLatform (COVERALL), we assessed the vaccine efficacy of the first two licensed SARS-CoV-2 vaccines in Switzerland and the functionality of the trial platform. Results Using Research Electronic Data Capture (REDCap), we developed a trial platform integrating the infrastructure of the SHCS and STCS. An algorithm identifying eligible patients, as well as baseline data transfer ensured a fast inclusion procedure for eligible patients. We implemented convenient re-directions between the different data entry systems to ensure intuitive data entry for the participating study personnel. The trial platform, including a randomization algorithm ensuring balance among different subgroups, was continuously adapted to changing guidelines concerning vaccination policies. We were able to randomize and vaccinate the first trial participant the same day we received ethics approval. Time to enroll and randomize our target sample size of 380 patients was 22 days. Conclusion Taking the best of each system, we were able to flag eligible patients, transfer patient information automatically, randomize and enroll the patients in an easy workflow, decreasing the administrative burden usually associated with a trial of this size.

One of the most prolific fields of research in biblical studies in the twenty-first century – in both Old and New Testament studies – is the analysis of biblical texts in relation to the events of the Neo-Babylonian conquests of Judah. The first conquest led to a surrender in 597 BCE, which was followed by a second, destructive, conquest of Jerusalem and surrounding areas in 586 BCE. Both conquests were accompanied by substantial deportations of Judeans into the Mesopotamian heartland. In addition to continued debates on about the historical events themselves, and the challenge of reading different biblical texts in relation to these historical events, the ‘exile’ has also been the focus of ongoing discussions in biblical theology. This attention to ‘exile’ has taken two different forms: through an analysis of the theology of the texts themselves in their own times; and through modern theological reflections on ‘exile’ as a theme. The latter approach appears in twenty-first century proposals for a (mainly Christian) biblical theology, which takes these historical events seriously, and examines how they inform contemporary Christian faith and practice. Finally, discussion on ‘exile’ themes in theology now incorporates scholars in both Old and New Testament work.

BackgroundProviding user-friendly electronic data collection tools for large multicenter studies is key for obtaining high-quality research data. Research Electronic Data Capture (REDCap) is a software solution developed for setting up research databases with integrated graphical user interfaces for electronic data entry. The Swiss Mother and Child HIV Cohort Study (MoCHiV) is a longitudinal cohort study with around 2 million data entries dating back to the early 1980s. Until 2022, data collection in MoCHiV was paper-based. ObjectiveThe objective of this study was to provide a user-friendly graphical interface for electronic data entry for physicians and study nurses reporting MoCHiV data. MethodsMoCHiV collects information on obstetric events among women living with HIV and children born to mothers living with HIV. Until 2022, MoCHiV data were stored in an Oracle SQL relational database. In this project, R and REDCap were used to develop an electronic data entry platform for MoCHiV with migration of already collected data. ResultsThe key steps for providing an electronic data entry option for MoCHiV were (1) design, (2) data cleaning and formatting, (3) migration and compliance, and (4) add-on features. In the first step, the database structure was defined in REDCap, including the specification of primary and foreign keys, definition of study variables, and the hierarchy of questions (termed “branching logic”). In the second step, data stored in Oracle were cleaned and formatted to adhere to the defined database structure. Systematic data checks ensured compliance to all branching logic and levels of categorical variables. REDCap-specific variables and numbering of repeated events for enabling a relational data structure in REDCap were generated using R. In the third step, data were imported to REDCap and then systematically compared to the original data. In the last step, add-on features, such as data access groups, redirections, and summary reports, were integrated to facilitate data entry in the multicenter MoCHiV study. ConclusionsBy combining different software tools—Oracle SQL, R, and REDCap—and building a systematic pipeline for data cleaning, formatting, and comparing, we were able to migrate a multicenter longitudinal cohort study from Oracle SQL to REDCap. REDCap offers a flexible way for developing customized study designs, even in the case of longitudinal studies with different study arms (ie, obstetric events, women, and mother-child pairs). However, REDCap does not offer built-in tools for preprocessing large data sets before data import. Additional software is needed (eg, R) for data formatting and cleaning to achieve the predefined REDCap data structure.

Este trabajo revisa la caracterización de Gilles Deleuze como un pensador anti-dialéctico y anti-hegeliano (fomentada tanto por la literatura secundaria como por el propio Deleuze), concentrándose en los matices que vuelven a estas caracterizaciones incompletas o inadecuadas. Estos matices son retomados desde tres momentos: 1° las condiciones históricas y biográficas en las cuales Deleuze es educado y formado como filósofo (donde una estricta escuela de historia de la filosofía, y en particular la tríada Hegel-Husserl-Heidegger, conforman la hegemonía académica); 2° el método propio que Deleuze desarrolla para trabajar con autores de la tradición de la historia de la filosofía (conduciendo a estos autores a su “límite diferencial”); 3° el modo en que Deleuze se alinea con la tradición poskantiana, bajo la influencia fundamental de Salomon Maimon (quien reclamaba para la crítica trascendental un método genético e inmanente). Finalmente, se perfilan algunos lineamientos sobre los cuales pensar la relación entre el proyecto deleuziano de una dialéctica diferencial, centrada en la categoría de problema, y el proyecto hegeliano, centrado en la contradicción y la negación.

The Fourier transform infrared microspectroscopy (FTIRm) system of the Australian Synchrotron has a unique optical configuration with a peculiar beam profile consisting of two parallel lines. The beam is tightly focused using a 36× Schwarzschild objective to a point on the sample and the sample is scanned pixel by pixel to record an image of a single plane using a single pixel mercury cadmium telluride detector. A computational stitching procedure is used to obtain a 2D image of the sample. However, if the imaging condition is not satisfied, then the recorded object’s information is distorted. Unlike commonly observed blurring, the case with a Schwarzschild objective is unique, with a donut like intensity distribution with three distinct lobes. Consequently, commonly used deblurring methods are not efficient for image reconstruction. In this study, we have applied a recently developed computational reconstruction method called the Lucy–Richardson–Rosen algorithm (LRRA) in the online FTIRm system for the first time. The method involves two steps: training step and imaging step. In the training step, the point spread function (PSF) library is recorded by temporal summation of intensity patterns obtained by scanning the pinhole in the x-y directions across the path of the beam using the single pixel detector along the z direction. In the imaging step, the process is repeated for a complicated object along only a single plane. This new technique is named coded aperture scanning holography. Different types of samples, such as two pinholes; a number 3 USAF object; a cross shaped object on a barium fluoride substrate; and a silk sample are used for the demonstration of both image recovery and 3D imaging applications.

Data competitions have become a popular approach to crowdsource new data analysis methods for general and specialized data science problems. Data competitions have a rich history in plant phenotyping, and new outdoor field datasets have the potential to embrace solutions across research and commercial applications. We developed the Global Wheat Challenge as a generalization competition in 2020 and 2021 to find more robust solutions for wheat head detection using field images from different regions. We analyze the winning challenge solutions in terms of their robustness when applied to new datasets. We found that the design of the competition had an influence on the selection of winning solutions and provide recommendations for future competitions to encourage the selection of more robust solutions.

Abstract HLA-G is a promiscuous immune checkpoint molecule. The HLA-G gene presents substantial nucleotide variability in its regulatory regions. However, it encodes a limited number of proteins compared to classical HLA class I genes. We characterized the HLA-G genetic variability in 4640 individuals from 88 different population samples across the globe by using a state-of-the-art method to characterize polymorphisms and haplotypes from high-coverage next-generation sequencing data. We also provide insights regarding the HLA-G genetic diversity and a resource for future studies evaluating HLA-G polymorphisms in different populations and association studies. Despite the great haplotype variability, we demonstrated that: (1) most of the HLA-G polymorphisms are in introns and regulatory sequences, and these are the sites with evidence of balancing selection, (2) linkage disequilibrium is high throughout the gene, extending up to HLA-A, (3) there are few proteins frequently observed in worldwide populations, with lack of variation in residues associated with major HLA-G biological properties (dimer formation, interaction with leukocyte receptors). These observations corroborate the role of HLA-G as an immune checkpoint molecule rather than as an antigen-presenting molecule. Understanding HLA-G variability across populations is relevant for disease association and functional studies.

Abstract Background Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. Methods We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, “COVID-19”). Discussion This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. Trial registration ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021

The CIPHR group, Institute of Physics, University of Tartu, Estonia, and Optical Sciences Center, Swinburne University of Technology, Australia, jointly organized the interdisciplinary online conference “Holography Meets Advanced Manufacturing” during 20–22 February 2023.

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Abstract Background Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p

Abstract Background Treatment Resistant Bipolar Depression (TRBD) is a major contributor to the burden of disease associated with Bipolar Disorder (BD). Treatment options for people experiencing bipolar depression are limited to three interventions listed by National Institute for Health and Care: lamotrigine, quetiapine and olanzapine, of which the latter two are often not well tolerated. The majority of depressed people with BD are therefore prescribed antidepressants despite limited efficacy. This demonstrates an unmet need for additional interventions. Pramipexole has been shown to improve mood symptoms in animal models of depression, in people with Parkinson’s Disease and two proof of principle trials of pramipexole for people with BD who are currently depressed. Methods The PAX-BD study, funded by the United Kingdom (UK) National Institute for Health Research, aims to extend previous findings by assessing the efficacy, safety and health economic impact of pramipexole in addition to mood stabilisers for patients with TRBD. A randomised, double-blind, placebo controlled design is conducted in a naturalistic UK National Health Service setting. An internal pilot study to examine feasibility and acceptability of the study design is included. Participants with TRBD are screened from National Health Service secondary care services in up to 40 mental health trusts in the UK, with the aim of recruiting approximately 414 participants into a pre-randomisation phase to achieve a target of 290 randomised participants. Primary safety and efficacy measures are at 12 weeks following randomisation, with follow up of participants to 52 weeks. The primary outcome is depressive symptoms as measured by Quick Inventory for Depressive Symptomatology – Self Report. Secondary outcomes include changes in anxiety, manic symptoms, tolerability, acceptability, quality of life and cost-effectiveness. Outcome measures are collected remotely using self-report tools implemented online, and observer-rated assessments conducted via telephone. ANCOVA will be used to examine the difference in rating scale scores between treatment arms, and dependent on compliance in completion of weekly self-report measures. A mixed effects linear regression model may also be used to account for repeated measures. Trial registration ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939 Protocol Version: 04-FEB-2021, Version 9.0.

Cryptococcus neoformans is a human pathogenic fungus that can cause pulmonary infections and meningitis in both immunocompromised and otherwise healthy individuals. Limited treatment options and a high mortality rate underlie the necessity for extensive research of the virulence of C. neoformans. Here we describe a detailed protocol for using the Galleria mellonella (Greater Wax Moth) larvae as a model organism for the virulence analysis of the cryptococcal infections. This protocol describes in detail the evaluation of G. mellonella larvae viability and the alternatives for troubleshooting the infection procedure. This protocol can be easily modified to study different inocula or fungal species, or the effects of a drug or antifungal agent on fungal disease within the larvae. We describe modified alternative versions of the protocol that allow using G. mellonella to study fungal diseases with different inocula and at different temperatures.

Objective To use a Scottish national linked diabetes care dataset to determine whether annual monitoring of clinical guideline-recommended diabetes care indicators differ by severe mental illness (SMI) status among people with type 2 diabetes (T2D) during the first year following diabetes diagnosis and thereafter. Approach We examined receipt of 9 diabetes care indicators (HbA1c; cholesterol; urinary albumin; serum creatinine; blood pressure; retinopathy screening; foot examination; body mass index; and smoking status) in people with T2D diagnosed 2009-2018, comparing people with a prior hospital record of schizophrenia, bipolar disorder and depression versus no hospital record for any mental illness. We analysed receipt of care in the first year using logistic regression and for the entire follow-up period (until death or 31 December 2018) using generalized linear mixed effects models, adjusting for calendar year, sociodemographic and lifestyle factors and comorbidities (and in the latter, diabetes duration). Results We included 119,508 people with T2D (mean age 59.7 [±13.2 SD]), of which 1701 (1%), 768 (0.5%) and 5211 (3%) had schizophrenia, bipolar disorder and depression, respectively. During the first year, compared to people without mental illness those with each SMI were more likely to receive cholesterol and serum creatinine measurement and, for schizophrenia only, HbA1c measurement, after adjustment for confounding factors. People with depression had higher odds of receiving a smoking review, but lower odds of receiving urinary albumin measurement. Receipt of all other indicators were similar across comparison groups. In the longitudinal analyses, people with schizophrenia had persistently higher odds of receiving HbA1c and people with a SMI had lower odds of receiving retinopathy screening. Conclusion Receipt of care delivered in the primary care setting was generally similar in people with versus without SMI in the short and long term. However, people with SMI were less likely to receive retinopathy screening, highlighting a need for better monitoring of care indicators delivered outside primary care settings.

BackgroundChronic diseases contribute to high rates of disability and mortality. Patient engagement in chronic disease self-management is an essential component of chronic disease models of health care. Wearables provide patient-centered health data in real time, which can help inform self-management decision-making. Despite the perceived benefits of wearables in improving chronic disease self-management, their influence on health care outcomes remains poorly understood. ObjectiveThis review aimed to examine the influence of wearables on health care outcomes in individuals with chronic diseases through a systematic review of the literature. MethodsA narrative systematic review was conducted by searching 6 databases for randomized and observational studies published between January 1, 2016, and July 1, 2021, that included the use of a wearable intervention in a chronic disease group to assess its impact on a predefined outcome measure. These outcomes were defined as any influence on the patient or clinician experience, cost-effectiveness, or health care outcomes as a result of the wearable intervention. Data from the included studies were extracted based on 6 key themes, which formed the basis for a narrative qualitative synthesis. All outcomes were mapped against each component of the Quadruple Aim of health care. The guidelines of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement were followed in this study. ResultsA total of 30 articles were included; studies reported 2446 participants (mean age: range 10.1-74.4 years), and the influence of 14 types of wearables on 18 chronic diseases was presented. The most studied chronic diseases were type 2 diabetes (4/30, 13%), Parkinson disease (3/30, 10%), and chronic lower back pain (3/30, 10%). The results were mixed when assessing the impact on a predefined primary outcome, with 50% (15/30) of studies finding a positive influence on the studied outcome and 50% (15/30) demonstrating a nil effect. There was a positive effect of 3D virtual reality systems on chronic pain in 7% (2/30) of studies that evaluated 2 distinct chronic pain syndromes. Mixed results were observed in influencing exercise capacity; weight; and biomarkers of disease, such as hemoglobin A1c, in diabetes. In total, 155 outcomes were studied. Most (139/155, 89.7%) addressed the health care outcomes component. This included pain (11/155, 7.5%), quality of life (7/155, 4.8%), and physical function (5/155, 3.4%). Approximately 7.7% (12/155) of outcome measures represented the patient experience component, with 1.3% (2/155) addressing the clinician experience and cost. ConclusionsGiven their popularity and capability, wearables may play an integral role in chronic disease management. However, further research is required to generate a strong evidence base for safe and effective implementation. Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42021244562; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=244562

Background: Longitudinal studies are crucial for identifying potential risk factors for infection with, and consequences of, COVID-19, but relationships can be biased if they are associated with invitation and response to data collection. We describe factors relating to questionnaire invitation and response in COVID-19 questionnaire data collection in a multigenerational birth cohort (the Avon Longitudinal Study of Parents and Children, ALSPAC). Methods: We analysed online questionnaires completed between the beginning of the pandemic and easing of the first UK lockdown by participants with valid email addresses who had not actively disengaged from the study. We assessed associations of pre-pandemic sociodemographic, behavioural, anthropometric and health-related factors with: i) being sent a questionnaire; ii) returning a questionnaire; and iii) item response (for specific questions). Analyses were conducted in three cohorts: the index children born in the early 1990s (now young adults; 41 variables assessed), their mothers (35 variables) and the mothers’ partners (27 variables). Results: Of 14,849 young adults, 41% were sent a questionnaire, of whom 57% returned one. Item response was >95%. In this cohort, 78% of factors were associated with being sent a questionnaire, 56% with returning one, and, as an example of item response, 20% with keyworker status response. For instance, children from mothers educated to degree-level had greater odds of being sent a questionnaire (OR=5.59; 95% CI=4.87-6.41), returning one (OR=1.60; 95% CI=1.31-1.95), and responding to items (e.g., keyworker status OR=1.65; 95% CI=0.88-3.04), relative to children from mothers with fewer qualifications. Invitation and response rates and associations were similar in all cohorts. Conclusions: These results highlight the importance of considering potential biases due to non-response when using longitudinal studies in COVID-19 research and interpreting results. We recommend researchers report response rates and factors associated with invitation and response in all COVID-19 observational research studies, which can inform sensitivity analyses.

Herein, we give an overview of several less explored structural and optical characterization techniques useful for biomaterials. New insights into the structure of natural fibers such as spider silk can be gained with minimal sample preparation. Electromagnetic radiation (EMR) over a broad range of wavelengths (from X-ray to THz) provides information of the structure of the material at correspondingly different length scales (nm-to-mm). When the sample features, such as the alignment of certain fibers, cannot be characterized optically, polarization analysis of the optical images can provide further information on feature alignment. The 3D complexity of biological samples necessitates that there be feature measurements and characterization over a large range of length scales. We discuss the issue of characterizing complex shapes by analysis of the link between the color and structure of spider scales and silk. For example, it is shown that the green-blue color of a spider scale is dominated by the chitin slab’s Fabry–Pérot-type reflectivity rather than the surface nanostructure. The use of a chromaticity plot simplifies complex spectra and enables quantification of the apparent colors. All the experimental data presented herein are used to support the discussion on the structure–color link in the characterization of materials.

Ultra-short laser pulses (1030 nm/230 fs) were used to laser ablate the surface of crystalline sapphire (Al2O3) at high intensity per pulse 20–200 TW/cm2/pulse. Laser-ablated patterns were annealed at a high temperature of 1500 °C. Surface reconstruction took place, removing the ablation debris field at the edges of ablated pits in oxygen flow (O2 flow). Partial reconstruction of ripples was also observed when multi-pulse ablated surfaces were annealed at high temperature in O2 flow. Back-side ablation of a 0.5-mm-thick Al2O3 produced high surface roughness ∼1μm which was reduced to ∼0.2μm by high-temperature annealing at 1500 °C for 2 h in O2. Improvement of surface quality was due to restructuring of the crystalline surface and sublimation, while the defined 3D shape of a micro-lens was not altered after HTA (no thermal morphing).

Pattern recognition techniques form the heart of most, if not all, incoherent linear shift-invariant systems. When an object is recorded using a camera, the object information is sampled by the point spread function (PSF) of the system, replacing every object point with the PSF in the sensor. The PSF is a sharp Kronecker Delta-like function when the numerical aperture (NA) is large with no aberrations. When the NA is small, and the system has aberrations, the PSF appears blurred. In the case of aberrations, if the PSF is known, then the blurred object image can be deblurred by scanning the PSF over the recorded object intensity pattern and looking for pattern matching conditions through a mathematical process called correlation. Deep learning-based image classification for computer vision applications gained attention in recent years. The classification probability is highly dependent on the quality of images as even a minor blur can significantly alter the image classification results. In this study, a recently developed deblurring method, the Lucy-Richardson-Rosen algorithm (LR2A), was implemented to computationally refocus images recorded in the presence of spatio-spectral aberrations. The performance of LR2A was compared against the parent techniques: Lucy-Richardson algorithm and non-linear reconstruction. LR2A exhibited a superior deblurring capability even in extreme cases of spatio-spectral aberrations. Experimental results of deblurring a picture recorded using high-resolution smartphone cameras are presented. LR2A was implemented to significantly improve the performances of the widely used deep convolutional neural networks for image classification.

Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those with mild and severe disease, but IgG levels increased early only in those with severe disease. A similar pattern was observed in a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from severe COVID-19.

Abstract Background Gateway courses are increasingly popular widening participation routes into medicine. These six year courses provide a more accessible entry route into medical school and aim to support under-represented students’ progress and graduation as doctors. There is little evidence on the performance of gateway students and this study compares attainment and aptitude on entry, and outcomes at graduation of students on the UK’s three longest running gateway courses with students studying on a standard entry medical degree (SEMED) course at the same institutions. Methods Data were obtained from the UK Medical Education Database for students starting between 2007 and 2012 at three UK institutions. These data included A-levels and Universities Clinical Aptitude Test scores on entry to medical school and the Educational Performance Measure (EPM) decile, Situational Judgement Test (SJT) and Prescribing Safety Assessment (PSA) scores as outcomes measures. Multiple regression models were used to test for difference in outcomes between the two types of course, controlling for attainment and aptitude on entry. Results Four thounsand three hundred forty students were included in the analysis, 560 on gateway courses and 3785 on SEMED courses. Students on SEMED courses had higher attainment (Cohen’s d = 1.338) and aptitude (Cohen’s d = 1.078) on entry. On exit SEMED students had higher EPM scores (Cohen’s d = 0.616) and PSA scores (Cohen’s d = 0.653). When accounting for attainment and aptitude on entry course type is still a significant predictor of EPM and PSA, but the proportion of the variation in outcome explained by course type drops from 6.4 to 1.6% for EPM Decile and from 5.3% to less than 1% for the PSA score. There is a smaller significant difference in SJT scores, with SEMED having higher scores (Cohen’s d = 0.114). However, when measures of performance on entry are accounted for, course type is no longer a significant predictor of SJT scores. Conclusions This study shows the differences of the available measures between gateway students and SEMED students on entry to their medical degrees are greater than the differences on exit. This provides modest evidence that gateway courses allow students from under-represented groups to achieve greater academic potential.

Stressors related to academic requisites, sport participation and pressure to perform may increase college athlete risk for mental health symptoms (Cox, Ross-Stewart, & Foltz, 2017; Sudano & Miles, 2017; Yang et al., 2007). The purpose of this study was to identify the level of clinically relevant self-reported mental health symptoms in National Collegiate Athletic Association (NCAA) Division III athletes and variations based on sport participation (i.e., men’s or women’s athletics; team or individual sports) over a two-year period. A nonexperimental, trend study design was used. Data analysis included descriptive statistics, chi square test, and multivariate analysis of variance (MANOVA) which used one-way analysis of variance (ANOVA) for follow-up procedures. A MANOVA revealed a significant interaction of gender and sport type for general symptoms [F(1, 564) = 9.583, p = .002] and depression [F(1, 564) = 6.945, p = .009] but not anxiety [F(1, 564) = 3.332, p = .068, ƞ2 = .006]. The project was able to describe mental health symptoms in a population that is not often included in the literature. Knowledge of collegiate athlete mental health prevalence is important because prevention and early intervention is a key component of community-based health programming.

We show that single-pulse burst fabrication will produce a flatter and smoother profile of axicons milled on sapphire compared to pulse overlapped fabrication which results in a damaged and much rougher surface. The fabrication of large-area (sub-1 cm cross-section) micro-optical components in a short period of time (∼10 min) and with less processing steps is highly desirable and would be cost-effective. Our results were achieved with femtosecond laser fabrication technology which has revolutionized the field of advanced manufacturing. This study compares three configurations of axicons such as the conventional axicon, a photon sieve axicon (PSA) and a sparse PSA directly milled onto a sapphire substrate. Debris of redeposited amorphous sapphire were removed using isopropyl alcohol and potassium hydroxide. A spatially incoherent illumination was used to test the components for imaging applications. Non-linear reconstruction was used for cleaning noisy images generated by the axicons.

Microlens arrays (MLAs) which are increasingly popular micro-optical elements in compact integrated optical systems were fabricated using a femtosecond direct laser write (fs-DLW) technique in the low-shrinkage SZ2080TM photoresist. High-fidelity definition of 3D surfaces on IR transparent CaF2 substrates allowed to achieve ∼50% transmittance in the chemical fingerprinting spectral region 2–5 μm wavelengths since MLAs were only ∼10 μm high corresponding to the numerical aperture of 0.3 (the lens height is comparable with the IR wavelength). To combine diffractive and refractive capabilities in miniaturised optical setup, a graphene oxide (GO) grating acting as a linear polariser was also fabricated by fs-DLW by ablation of a 1 μm-thick GO thin film. Such an ultra-thin GO polariser can be integrated with the fabricated MLA to add dispersion control at the focal plane. Pairs of MLAs and GO polarisers were characterised throughout the visible–IR spectral window and numerical modelling was used to simulate their performance. A good match between the experimental results of MLA focusing and simulations was achieved.

Ultra-short 230 fs laser pulses of a 515 nm wavelength were tightly focused onto 700 nm focal spots and utilised in opening ∼0.4–1 μm holes in alumina Al2O3 etch masks with a 20–50 nm thickness. Such dielectric masks simplify the fabrication of photonic crystal (PhC) light-trapping patterns for the above-Lambertian performance of high-efficiency solar cells. The conditions of the laser ablation of transparent etch masks and the effects sub-surface Si modifications were revealed by plasma etching, numerical modelling, and minority carrier lifetime measurements. Mask-less patterning of Si is proposed using fs laser direct writing for dry plasma etching of Si.

Activating epidermal growth factor receptor gene mutations (EGFRm) are relatively common in non-small cell lung cancer (NSCLC) and are predictive of superior outcomes with EGFR tyrosine kinase inhibitors (TKIs). Eventually, acquired genetic or phenotypic resistance overcomes EGFR TKI therapy. Heterogeneity of acquired anti-EGFR resistance mechanisms is increasingly described, presenting a significant challenge in their clinical management. Here, we report a rare case of concurrent acquired EGFRT790M and small cell lung cancer transformation in a patient with EGFR exon 21-L858R mutant lung adenocarcinoma, following treatment with a second-generation EGFR TKI. The case highlights the clinical significance of serial EGFR genotyping with peripheral ctDNA alongside targeted biopsies, for the detection of genetic and phenotypic resistance mechanisms to EGFR TKIs, which can occur concurrently. This case provides further evidence in favour of upfront treatment approaches that target the heterogeneity of acquired anti-EGFR resistance mechanisms, such as experimental combinations of cytotoxic chemotherapy with a third-generation EGFR TKI.

OBJECTIVES:. To compare the performance of Sequential Organ Failure Assessment, systemic inflammatory response syndrome, Red Flag Sepsis, and National Institute of Clinical Excellence sepsis risk stratification tools in the identification of patients at greatest risk of mortality from sepsis in nonintensive care environments. DESIGN:. Secondary analysis of three annual 24-hour point-prevalence study periods. SETTING:. The general wards and emergency departments of 14 acute hospitals across Wales. Studies were conducted on the third Wednesday of October in 2017, 2018, and 2019. PATIENTS:. We screened all patients presenting to the emergency department and on the general wards. MEASUREMENTS AND MAIN RESULTS:. We recruited 1,271 patients, of which 724 (56.9%) had systemic inflammatory response syndrome greater than or equal to 2, 679 (53.4%) had Sequential Organ Failure Assessment greater than or equal to 2, and 977 (76.9%) had Red Flag Sepsis. When stratified according to National Institute of Clinical Excellence guidelines, 450 patients (35.4%) were in the “High risk” category in comparison with 665 (52.3%) in “Moderate to High risk” and 156 (12.3%) in “Low risk” category. In a planned sensitivity analysis, we found that none of the tools accurately predicted mortality at 90 days, and Sequential Organ Failure Assessment and National Institute of Clinical Excellence tools showed only moderate discriminatory power for mortality at 7 and 14 days. Furthermore, we could not find any significant correlation with any of the tools at any of the mortality time points. CONCLUSIONS:. Our data suggest that the sepsis risk stratification tools currently utilized in emergency departments and on the general wards do not predict mortality adequately. This is illustrated by the disparity in mortality risk of the populations captured by each instrument, as well as the weak concordance between them. We propose that future studies on the development of sepsis identification tools should focus on identifying predicator values of both the short- and long-term outcomes of sepsis.

Objectives We aimed to examine agreement between common mental disorders (CMDs) from primary care records and repeated CMD questionnaire data from ALSPAC (the Avon Longitudinal Study of Parents and Children) over adolescence and young adulthood, explore factors affecting CMD identification in primary care records, and construct models predicting ALSPAC-derived CMDs using only primary care data.Design and setting Prospective cohort study (ALSPAC) in Southwest England with linkage to electronic primary care records.Participants Primary care records were extracted for 11 807 participants (80% of 14 731 eligible). Between 31% (3633; age 15/16) and 11% (1298; age 21/22) of participants had both primary care and ALSPAC CMD data.Outcome measures ALSPAC outcome measures were diagnoses of suspected depression and/or CMDs. Primary care outcome measure were Read codes for diagnosis, symptoms and treatment of depression/CMDs. For each time point, sensitivities and specificities for primary care CMD diagnoses were calculated for predicting ALSPAC-derived measures of CMDs, and the factors associated with identification of primary care-based CMDs in those with suspected ALSPAC-derived CMDs explored. Lasso (least absolute selection and shrinkage operator) models were used at each time point to predict ALSPAC-derived CMDs using only primary care data, with internal validation by randomly splitting data into 60% training and 40% validation samples.Results Sensitivities for primary care diagnoses were low for CMDs (range: 3.5%–19.1%) and depression (range: 1.6%–34.0%), while specificities were high (nearly all >95%). The strongest predictors of identification in the primary care data for those with ALSPAC-derived CMDs were symptom severity indices. The lasso models had relatively low prediction rates, especially in the validation sample (deviance ratio range: −1.3 to 12.6%), but improved with age.Conclusions Primary care data underestimate CMDs compared to population-based studies. Improving general practitioner identification, and using free-text or secondary care data, is needed to improve the accuracy of models using clinical data.

Direct imaging systems that create an image of an object directly on the sensor in a single step are prone to many constraints, as a perfect image is required to be recorded within this step. In designing high resolution direct imaging systems with a diffractive lens, the outermost zone width either reaches the lithography limit or the diffraction limit itself, imposing challenges in fabrication. However, if the imaging mode is switched to an indirect one consisting of multiple steps to complete imaging, then different possibilities open. One such method is the widely used indirect imaging method with Golay configuration telescopes. In this study, a Golay-like configuration has been adapted to realize a large-area diffractive lens with three sub-aperture diffractive lenses. The sub-aperture diffractive lenses are not required to collect light and focus them to a single point as in a direct imaging system, but to focus independently on different points within the sensor area. This approach of a Large-Area Diffractive lens with Integrated Sub-Apertures (LADISA) relaxes the fabrication constraints and allows the sub-aperture diffractive elements to have a larger outermost zone width and a smaller area. The diffractive sub-apertures were manufactured using photolithography. The fabricated diffractive element was implemented in indirect imaging mode using non-linear reconstruction and the Lucy–Richardson–Rosen algorithm with synthesized point spread functions. The computational optical experiments revealed improved optical and computational imaging resolutions compared to previous studies.

Phase imaging of biochemical samples has been demonstrated for the first time at the Infrared Microspectroscopy (IRM) beamline of the Australian Synchrotron using the usually discarded near-IR (NIR) region of the synchrotron-IR beam. The synchrotron-IR beam at the Australian Synchrotron IRM beamline has a unique fork shaped intensity distribution as a result of the gold coated extraction mirror shape, which includes a central slit for rejection of the intense X-ray beam. The resulting beam configuration makes any imaging task challenging. For intensity imaging, the fork shaped beam is usually tightly focused to a point on the sample plane followed by a pixel-by-pixel scanning approach to record the image. In this study, a pinhole was aligned with one of the lobes of the fork shaped beam and the Airy diffraction pattern was used to illuminate biochemical samples. The diffracted light from the samples was captured using a NIR sensitive lensless camera. A rapid phase-retrieval algorithm was applied to the recorded intensity distributions to reconstruct the phase information. The preliminary results are promising to develop multimodal imaging capabilities at the IRM beamline of the Australian Synchrotron.

To enhance the solubility of orally administered pharmaceuticals, liquid capsules or amorphous tablets are often preferred over crystalline drug products. However, little is known regarding the variation in bonding mechanisms between pharmaceutical molecules in their different disordered forms. In this study, liquid and melt-quenched glassy carbamazepine have been studied using high energy X-ray diffraction and modeled using Empirical Potential Structure Refinement. The results show significant structural differences between the liquid and glassy states. The liquid shows a wide range of structures; from isolated molecules, to aromatic ring correlations and NH-O hydrogen bonding. Upon quenching from the liquid to the glass the number of hydrogen bonds per molecule increases by ~50% at the expense of a ~30% decrease in the close contact (non-bonded) carbon-carbon interactions between aromatic rings. During the cooling process, there is an increase in both singly and doubly hydrogen-bonded adjacent molecules. Although hydrogen-bonded dimers found in the crystalline states persist in the glassy state, the absence of a crystalline lattice also allows small, hydrogen-bonded NH-O trimers and tetramers to form. This proposed model for the structure of glassy carbamazepine is consistent with the results from vibrational spectroscopy and nuclear magnetic resonance.