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We aimed to explore, in a sample of systematic reviews (SRs) with meta-analyses of the association between food/diet and health-related outcomes, whether systematic reviewers selectively included study effect estimates in meta-analyses when multiple effect estimates were available. We randomly selected SRs of food/diet and health-related outcomes published between January 2018 and June 2019. We selected the first presented meta-analysis in each review (index meta-analysis), and extracted from study reports all study effect estimates that were eligible for inclusion in the meta-analysis. We calculated the Potential Bias Index (PBI) to quantify and test for evidence of selective inclusion. The PBI ranges from 0 to 1; values above or below 0.5 suggest selective inclusion of effect estimates more or less favourable to the intervention, respectively. We also compared the index meta-analytic estimate to the median of a randomly constructed distribution of meta-analytic estimates (i.e., the estimate expected when there is no selective inclusion). Thirty-nine SRs with 312 studies were included. The estimated PBI was 0.49 (95% CI 0.42-0.55), suggesting that the selection of study effect estimates from those reported was consistent with a process of random selection. In addition, the index meta-analytic effect estimates were similar, on average, to what we would expect to see in meta-analyses generated when there was no selective inclusion. Despite this, we recommend that systematic reviewers report the methods used to select effect estimates to include in meta-analyses, which can help readers understand the risk of selective inclusion bias in the SRs.

Abstract High-dimensional quantum states are known to offer advantages over their two-dimensional qubit counterparts, but their preparation and manipulation has been bulky and cumbersome. Now, quantum state control has been demonstrated on-chip with a ~1 μm2 footprint and nm-scale features, producing up to eight-dimensional quantum states and ushering in a new route to large quantum information encoding on a small footprint.

Abstract Transparent objects are invisible to traditional cameras because they can only detect intensity fluctuations, necessitating the need for interferometry followed by computationally intensive digital image processing. Now it is shown that the necessary transformations can be performed optically by combining machine learning and diffractive optics, for a direct in-situ measurement of transparent objects with conventional cameras.

ABSTRACTStructured light refers to the ability to tailor light in its many degrees of freedom, from the traditional control in time and space to more exotic multi-dimensional control for new forms of light, including vectorial light, toroidal excitations, spatio-temporal vortices, skyrmions, and optical mobius strips to name but a few. While the toolbox for the creation and detection of structured light has advanced tremendously, this has mostly been in the low power regime. More recently, structured light at high-power and high-intensities has emerged, fuelling new science and applications. In this progress report, we showcase the seminal work that has advanced this field, and indicate the open challenges and opportunities that remain.

Abstract Information exchange between two distant parties, where information is shared without physically transporting it, is a crucial resource in future quantum networks. Doing so with high-dimensional states offers the promise of higher information capacity and improved resilience to noise, but progress to date has been limited. Here we demonstrate how a nonlinear parametric process allows for arbitrary high-dimensional state projections in the spatial degree of freedom, where a strong coherent field enhances the probability of the process. This allows us to experimentally realise quantum transport of high-dimensional spatial information facilitated by a quantum channel with a single entangled pair and a nonlinear spatial mode detector. Using sum frequency generation we upconvert one of the photons from an entangled pair resulting in high-dimensional spatial information transported to the other. We realise a d = 15 quantum channel for arbitrary photonic spatial modes which we demonstrate by faithfully transferring information encoded into orbital angular momentum, Hermite-Gaussian and arbitrary spatial mode superpositions, without requiring knowledge of the state to be sent. Our demonstration merges the nascent fields of nonlinear control of structured light with quantum processes, offering a new approach to harnessing high-dimensional quantum states, and may be extended to other degrees of freedom too.

Abstract Uncertainty relations are core to both classical and quantum physics, and lend themselves to tests across many degrees of freedom, with structured light emerging as a vibrant tool to harness these degrees of freedom. Here, we test Popper’s conjecture by replacing the traditional spatial and momentum states with angular position and orbital angular momentum (OAM) states of photons, showing that the OAM spectrum for an entangled photon passing through a virtual slit differs from that of a photon passing through a physical slit. To achieve this, we produce two OAM entangled photons, one of which is sent to a slit encoded as a digital hologram, thereby localising its angular position, all the while measuring the OAM of the other. We show that the measured OAM spectrum is limited to that of the initial SPDC photons, independent of the OAM encoded into the slit, consistent with Popper’s viewpoint. Our approach allows us to overcome prior limitations imposed by physical slits and linear momentum, and offers a versatile toolbox for further probes of quantum systems.

Background Systematic reviews that aim to synthesize evidence on the effects of interventions targeted at populations often include interrupted time-series (ITS) studies. However, the suppression of ITS studies or results within these studies (known as reporting bias) has the potential to bias conclusions drawn in such systematic reviews, with potential consequences for healthcare decision-making. Therefore, we aim to determine whether there is evidence of reporting bias among ITS studies. Methods We will conduct a search for published protocols of ITS studies and reports of their results in PubMed, MEDLINE, and Embase up to December 31, 2022. We contact the authors of the ITS studies to seek information about their study, including submission status, data for unpublished results, and reasons for non-publication or non-reporting of certain outcomes. We will examine if there is evidence of publication bias by examining whether time-to-publication is influenced by the statistical significance of the study’s results for the primary research question using Cox proportional hazards regression. We will examine whether there is evidence of discrepancies in outcomes by comparing those specified in the protocols with those in the reports of results, and we will examine whether the statistical significance of an outcome’s result is associated with how completely that result is reported using multivariable logistic regression. Finally, we will examine discrepancies between protocols and reports of results in the methods by examining the data collection processes, model characteristics, and statistical analysis methods. Discrepancies will be summarized using descriptive statistics. Discussion These findings will inform systematic reviewers and policymakers about the extent of reporting biases and may inform the development of mechanisms to reduce such biases.

Spatial light modulators, as dynamic flat-panel optical devices, have witnessed rapid development over the past two decades, concomitant with the advancements in micro- and opto-electronic integration technology. In particular, liquid-crystal spatial light modulator (LC-SLM) technologies have been regarded as versatile tools for generating arbitrary optical fields and tailoring all degrees of freedom beyond just phase and amplitude. These devices have gained significant interest in the nascent field of structured light in space and time, facilitated by their ease of use and real-time light manipulation, fueling both fundamental research and practical applications. Here we provide an overview of the key working principles of LC-SLMs and review the significant progress made to date in their deployment for various applications, covering topics as diverse as beam shaping and steering, holography, optical trapping and tweezers, measurement, wavefront coding, optical vortex, and quantum optics. Finally, we conclude with an outlook on the potential opportunities and technical challenges in this rapidly developing field.

Background: Clinical research in perioperative medicine requires the perspectives of patients and caregivers to increase its relevance and quality, benefiting both researchers and the community. Identifying these priorities will enable researchers, funders, and governing bodies to efficiently use scarce funding and resources. We aim to identify the top 10 research priorities in perioperative medical research in Australia. Methods: A mixed-methods, exploratory-sequential design will be conducted. The study will include five phases. Initially, a published open-ended survey gathered responses from the population (researchers, healthcare workers, and consumers) regarding uncertainties/questions relevant to the population about perioperative medical research. We collected 544 questions and quantitatively analysed and grouped them according to the Standardised Endpoints in Perioperative Medicine–Core Outcomes Measures in Perioperative and Anaesthetic Care (StEP–COMPAC) endpoints. Using multicriteria decision-making software, workshops combining the population will be conducted to determine the top 10 priorities for perioperative medicine research for the Australian population. Ethics and dissemination: Ethical approval to conduct the study was obtained from the Alfred Health (Australia) Human Research Ethics Committee (ID: 171/19). The findings will be disseminated in peer review publications, conferences, and dissemination across perioperative research networks. The top 10 priorities will be available to inform research funders, grant submissions, guidelines, and the population.

Introduction The use of high fraction of inspired oxygen (FiO2) intraoperatively for the prevention of surgical site infection (SSI) remains controversial. Promising results of early randomised controlled trials (RCT) have been replicated with varying success and subsequent meta-analysis are equivocal. Recent advancements in perioperative care, including the increased use of laparoscopic surgery and pneumoperitoneum and shifts in fluid and temperature management, can affect peripheral oxygen delivery and may explain the inconsistency in reproducibility. However, the published data provides insufficient detail on the participant level to test these hypotheses. The purpose of this individual participant data meta-analysis is to assess the described benefits and harms of intraoperative high FiO2compared with regular (0.21–0.40) FiO2 and its potential effect modifiers.Methods and analysis Two reviewers will search medical databases and online trial registries, including MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and WHO regional databases, for randomised and quasi-RCT comparing the effect of intraoperative high FiO2 (0.60–1.00) to regular FiO2 (0.21–0.40) on SSI within 90 days after surgery in adult patients. Secondary outcome will be all-cause mortality within the longest available follow-up. Investigators of the identified trials will be invited to collaborate. Data will be analysed with the one-step approach using the generalised linear mixed model framework and the statistical model appropriate for the type of outcome being analysed (logistic and cox regression, respectively), with a random treatment effect term to account for the clustering of patients within studies. The bias will be assessed using the Cochrane risk-of-bias tool for randomised trials V.2 and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. Prespecified subgroup analyses include use of mechanical ventilation, nitrous oxide, preoperative antibiotic prophylaxis, temperature (2.5 hour).Ethics and dissemination Ethics approval is not required. Investigators will deidentify individual participant data before it is shared. The results will be submitted to a peer-review journal.PROSPERO registration number CRD42018090261.

Rumen fluke (RF) are trematode parasites that have increased in prevalence within European ruminant livestock since the 1990s. Morbidity and mortality can result from the development of juvenile flukes in the duodenum, however, evidence for significant impacts of adult fluke in the rumen of the final host is equivocal. The presence of rumen fluke in Scotland had not previously been quantified, so the purpose of this study was to use historical coprological data collected between 2008 and 2018 at the School of Veterinary Medicine in Glasgow to evaluate the frequency of rumen fluke infection and to compare this with the presence of liver fluke. This analysis showed evidence of adult rumen fluke in 6.6% of samples submitted, with a substantial and significant increase in positive diagnoses from 2016, following which positive rumen fluke diagnoses equaled or slightly outnumbered those of liver fluke. A prospective post-mortem examination study was also carried out to determine the presence of rumen and liver fluke in cattle and sheep, to quantify adult rumen fluke burdens and to assess any pathological changes in the reticulorumen and proximal duodenum associated with infection. The presence of rumen fluke in post-mortem cases was 26.9% (n = 18/67), the majority (66.7%, n = 12/18) with burdens of less than 100 adult rumen flukes. There was no significant difference in mean ruminal papillar density and length in animals with and without adult rumen fluke and no significant gross pathology was observed in the rumen or reticulum. Examination of animals with adult rumen fluke provided no evidence of any consistent associations with acute or chronic inflammatory changes in the duodenum. All rumen fluke collected at necropsy were identified by PCR and sequencing as Calicophoron daubneyi.

Abstract Here we functionalized micro-scaled polymer beads with nano-scaled quantum dots and demonstrate optical trapping and tweezing, with in-situ fluorescence measurement, in an all-digital all-optical configuration. We outline the chemistry required to facilitate this, from deactivating the optical trapping environment to size, adhesion and agglomeration control. We introduce a novel holographic optical trapping set-up that leverages on vectorially structured light, allowing for the delivery of tuneable forms of light from purely scalar to purely vector, including propagation invariant flat-top beams for uniform illumination and tailored intensity gradient landscapes. Finally, we show how this has the potential to quench bleaching in a single wavelength trap by linear (spatial mode) rather than non-linear effects, advancing the nascent field of optics for chemistry.

Structured light has become topical of late, where controlling light in all its degrees of freedom has offered novel states of light long predicted, enhanced functionality in applications, and a modern toolbox for probing fundamental science. Structuring light as single photons and entangled states allows the spatial modes of light to be used to encode a large alphabet, accessing high dimensional Hilbert spaces for fundamental tests of quantum mechanics and improved quantum information processing tasks. In this tutorial, we outline the basic concepts of high dimensional quantum states expressed in a basis of spatial modes (structured light) and explain how to create, control, and detect such quantum states in the laboratory with a focus on transverse spatial modes such as the orbital angular momentum and pixel (position) modes. Finally, we highlight some example applications of such quantum structured light, from communications to imaging.

It is the first perspective or review that considers the dimensionality that may be reached with structured light, as well as the opportunities and challenges in pursuing this.

The interest in tailoring light in all its degrees of freedom is steadily gaining traction, driven by the tremendous developments in the toolkit for the creation, control and detection of what is now called structured light. Because the complexity of these optical fields is generally understood in terms of interference, the tools have historically been linear optical elements that create the desired superpositions. For this reason, despite the long and impressive history of nonlinear optics, only recently has the spatial structure of light in nonlinear processes come to the fore. In this review we provide a concise theoretical framework for understanding nonlinear optics in the context of structured light, offering an overview and perspective on the progress made, and the challenges that remain.

Abstract Quantum ghost imaging offers many advantages over classical imaging, including low photon fluxes and non-degenerate object and image wavelengths for imaging light sensitive structures, but suffers from slow image reconstruction speeds. Image reconstruction times depend on the resolution of the required image which scale quadratically with the image resolution. Here, we propose a super-resolved imaging approach based on neural networks where we reconstruct a low resolution image, which we denoise and super-resolve to a high resolution image. To test the approach, we implemented both a generative adversarial network as well as a super-resolving autoencoder in conjunction with an experimental quantum ghost imaging setup, demonstrating its efficacy across a range of object and imaging projective mask types. We achieved super-resolving enhancement of $$4\times$$ 4 × the measured resolution with a fidelity close to 90 $$\%$$ % at an acquisition time of N $$^2$$ 2 measurements, required for a complete N $$\times$$ × N pixel image solution. This significant resolution enhancement is a step closer to a common ghost imaging goal, to reconstruct images with the highest resolution and the shortest possible acquisition time.

Abstract It is well known that azobenzene-containing polymers (azopolymers) are sensitive to the polarization orientation of the illuminating radiation, with the resulting photoisomerization inducing material transfer at both the meso- and macroscale. As a result, azopolymers are efficient and versatile photonic materials, for example, they are used for the fabrication of linear diffraction gratings, including subwavelength gratings, microlens arrays, and spectral filters. Here we propose to use carbazole-containing azopolymer thin films to directly visualize the longitudinal component of the incident laser beam, a crucial task for the realization of 3D structured light yet remaining experimentally challenging. We demonstrate the approach on both scalar and vectorial states of structured light, including higher-order and hybrid cylindrical vector beams. In addition to detection, our results confirm that carbazole-containing azopolymers are a powerful tool material engineering with the longitudinal component of the electric field, particularly to fabricate microstructures with unusual morphologies that differentiate from the total intensity distribution of the writing laser beam.

Abstract Background Robot-assisted radical prostatectomy (RARP) rates have been increasing worldwide despite a lack of evidence of superior patient-reported outcomes (PROs) compared to open radical prostatectomy (ORP). Methods This retrospective study included men who contributed data to the Prostate Cancer Outcomes Registry-Victoria (PCOR-Vic), underwent ORP or RARP between January 2014 and May 2018, and completed the EPIC-26 questionnaire 12 months post-surgery. Urinary and sexual bother items, the urinary incontinence domain score, the urinary irritative/obstructive domain score, the sexual domain score and the pad usage item from the EPIC-26 questionnaire were compared between the two cohorts. Unmatched and propensity score matched cohorts were used to determine if there were differences in urinary and sexual PROs between ORP and RARP after accounting for the patient case-mix and surgeon characteristics. Results Of 3826 patients undergoing radical prostatectomy (RP), 1047 received ORP and 2779 received RARP. Propensity score matching reduced the magnitude of the observed differences in four out of six outcomes (urinary bother, urinary incontinence domain, pad usage and sexual domain). Using a propensity score matched cohort, there were no statistically significant differences for RARP patients, compared to ORP patients, in terms of urinary bother (Rd = 0.47%, P = 0.707), urinary incontinence domain scores (Coeff = − 0.84, P = 0.506), urinary irritative/obstructive domain scores (Coeff = 1.03, P = 0.105), pad usage (Rd = − 0.75%, P = 0.771) and sexual bother (Rd = − 0.89%, P = 0.731). RARP patients had slightly higher sexual domain scores (Coeff = 3.65, P = 0.005). Conclusion There were no differences in urinary PROs between ORP and RARP when assessed 12 months post-surgery. The sexual domain slightly favoured RARP, however this was not deemed clinically significant.

Abstract Background Knee osteoarthritis is a major cause of pain and disability. Pain control is poor, with most patients remaining in moderate to severe pain. This may be because central causes of pain, a common contributor to knee pain, are not affected by current treatment strategies. Antidepressants, such as amitriptyline, have been used to treat chronic pain in other conditions. The aim of this randomised, double blind, controlled trial, is to determine whether low dose amitriptyline reduces pain in people with painful knee osteoarthritis over 3 months compared to benztropine, an active placebo. Methods/design One hundred and sixty people with painful radiographic knee osteoarthritis will be recruited via clinicians, local and social media advertising. Participants will be randomly allocated in a 1:1 ratio to receive either low dose amitriptyline (25 mg) or active placebo (benztropine mesylate, 1 mg) for 3 months. The primary outcome is change from baseline in knee pain (WOMAC pain subscale) at 12 weeks. Secondary outcomes include change in function (total WOMAC) and the proportion of individuals achieving a substantial response (≥ 50% reduction in pain intensity, measured by Visual Analog Scale, VAS, from no pain to worst pain imaginable, 0-100 mm) and moderate response (≥ 30% reduction in pain intensity, measured by VAS) at 12 weeks. Intention to treat analyses will be performed. Subgroup analyses will be done. Discussion This study will provide high level evidence regarding the effectiveness of low dose amitriptyline compared to benztropine in reducing pain and improving function in knee OA. This trial has the potential to provide an effective new therapeutic approach for pain management in knee osteoarthritis, with the potential of ready translation into clinical practice, as it is repurposing an old drug, which is familiar to clinicians and with a well described safety record. Trial registration Australian New Zealand Clinical Trials Registry prior to recruitment commencing ( ACTRN12615000301561 , March 31, 2015, amended 14 December 2018, February 2021). Additional amendment requested 18 July 2021.

Quantifying dimensionality of high-dimensional entangled states is challenging, especially in the presence of mixedness and noise. Here, the authors propose and demonstrate a method to quantify the dimensionality and purity of a bi-photon HD entangled state, scaling linearly with entanglement dimension.

The Doppler effect is a wave phenomenon that can find the magnitude of velocity of moving targets with scalar waves. Here, the authors use vectorially structured light with spatially variant polarization to fully determine both the magnitude of velocity and motion direction of a moving particle.

Abstract Quantum ghost imaging offers many advantages over classical imaging, including the ability to probe an object with one wavelength and record the image with another (non-degenerate ghost imaging), but suffers from slow image reconstruction due to sparsity and probabilistic arrival positions of photons. Here, we propose a two-step deep learning approach to establish an optimal early stopping point based on object recognition, even for sparsely filled images. In step one we enhance the reconstructed image after every measurement by a deep convolutional auto-encoder, followed by step two in which a classifier is used to recognise the image. We test this approach on a non-degenerate ghost imaging setup while varying physical parameters such as the mask type and resolution. We achieved a fivefold decrease in image acquisition time at a recognition confidence of $$75\%$$ 75 % . The significant reduction in experimental running time is an important step towards real-time ghost imaging, as well as object recognition with few photons, e.g., in the detection of light sensitive structures.

Abstract Vector beams, non-separable in spatial mode and polarisation, have emerged as enabling tools in many diverse applications, from communication to imaging. This applicability has been achieved by sophisticated laser designs controlling the spin and orbital angular momentum, but so far is restricted to only two-dimensional states. Here we demonstrate the first vectorially structured light created and fully controlled in eight dimensions, a new state-of-the-art. We externally modulate our beam to control, for the first time, the complete set of classical Greenberger–Horne–Zeilinger (GHZ) states in paraxial structured light beams, in analogy with high-dimensional multi-partite quantum entangled states, and introduce a new tomography method to verify their fidelity. Our complete theoretical framework reveals a rich parameter space for further extending the dimensionality and degrees of freedom, opening new pathways for vectorially structured light in the classical and quantum regimes.

Abstract Background We consider the design of stepped wedge trials with continuous recruitment and continuous outcome measures. Suppose we recruit from a fixed number of clusters where eligible participants present continuously, and suppose we have fine control over when each cluster crosses to the intervention. Suppose also that we want to minimise the number of participants, leading us to consider “incomplete” designs (i.e. without full recruitment). How can we schedule recruitment and cross-over at different clusters to recruit efficiently while achieving good precision? Methods The large number of possible designs can make exhaustive searches impractical. Instead we consider an algorithm using iterative improvements to hunt for an efficient design. At each iteration (starting from a complete design) a single participant – the one with the smallest impact on precision – is removed, and small changes preserving total sample size are made until no further improvement in precision can be found. Results Striking patterns emerge. Solutions typically focus recruitment and cross-over on the leading diagonal of the cluster-by-time diagram, but in some scenarios clusters form distinct phases resembling before-and-after designs. Conclusions There is much to be learned about optimal design for incomplete stepped wedge trials. Algorithmic searches could offer a practical approach to trial design in complex settings generally.

Background: MicroRNAs (miRNAs) are sought-after biomarkers of complex, polygenic diseases such as type 2 diabetes (T2D). Data-driven biocomputing provides robust and novel avenues for synthesizing evidence from individual miRNA seq studies. Objective: To identify miRNA markers associated with T2D, via a data-driven, biocomputing approach on high throughput transcriptomics. Materials and methods: The pipeline consisted of five sequential steps using miRNA seq data retrieved from the National Center for Biotechnology Information Gene Expression Omnibus platform: systematic review; identification of differentially expressed miRNAs (DE-miRNAs); meta-analysis of DE-miRNAs; network analysis; and downstream analyses. Three normalization algorithms (trimmed mean of M-values; upper quartile; relative log expression) and two meta-analytic algorithms (robust rank aggregation; Fisher's method of p-value combining) were integrated into the pipeline. Network analysis was conducted on miRNet 2.0 while enrichment and over-representation analyses were conducted on miEAA 2.0. Results: A total of 1256 DE-miRNAs (821 downregulated; 435 upregulated) were identified from 5 eligible miRNA seq datasets (3 circulatory; 1 adipose; 1 pancreatic). The meta-signature comprised 9 miRNAs (hsa-miR-15b-5p; hsa-miR-33b-5p; hsa-miR-106b-3p; hsa-miR-106b-5p; hsa-miR-146a-5p; hsa-miR-483-5p; hsa-miR-539-3p; hsa-miR-1260a; hsa-miR-4454), identified via the two meta-analysis approaches. Two hub nodes (hsa-miR-106b-5p; hsa-miR-15b-5p) with above-average degree and betweenness centralities in the miRNA-gene interactions network were identified. Downstream analyses revealed 5 highly conserved- (hsa-miR-33b-5p; hsa-miR-15b-5p; hsa-miR-106b-3p; hsa-miR-106b-5p; hsa-miR-146a-5p) and 7 highly confident- (hsa-miR-33b-5p; hsa-miR-15b-5p; hsa-miR-106b-3p; hsa-miR-106b-5p; hsa-miR-146a-5p; hsa-miR-483-5p; hsa-miR-539-3p) miRNAs. A total of 288 miRNA-disease associations were identified, in which 3 miRNAs (hsa-miR-15b-5p; hsa-miR-106b-3p; hsa-miR-146a-5p) were highly enriched. Conclusions: A meta-signature of DE-miRNAs associated with T2D was discovered via in-silico analyses and its pathobiological relevance was validated against corroboratory evidence from contemporary studies and downstream analyses. The miRNA meta-signature could be useful for guiding future studies on T2D. There may also be avenues for using the pipeline more broadly for evidence synthesis on other conditions using high throughput transcriptomics.

IntroductionUsing body mass index (BMI) as a proxy, previous Mendelian randomization (MR) studies found total causal effects of general obesity on polycystic ovarian syndrome (PCOS). Hitherto, total and direct causal effects of general- and central obesity on PCOS have not been comprehensively analyzed.ObjectivesTo investigate the causality of central- and general obesity on PCOS using surrogate anthropometric markers.MethodsSummary GWAS data of female-only, large-sample cohorts of European ancestry were retrieved for anthropometric markers of central obesity (waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR)) and general obesity (BMI and its constituent variables-weight and height), from the IEU Open GWAS Project. As the outcome, we acquired summary data from a large-sample GWAS (118870 samples; 642 cases and 118228 controls) within the FinnGen cohort. Total causal effects were assessed via univariable two-sample Mendelian randomization (2SMR). Genetic architectures underlying causal associations were explored. Direct causal effects were analyzed by multivariable MR modelling.ResultsInstrumental variables demonstrated no weak instrument bias (F > 10). Four anthropometric exposures, namely, weight (2.69-77.05), BMI (OR: 2.90-4.06), WC (OR: 6.22-20.27), and HC (OR: 6.22-20.27) demonstrated total causal effects as per univariable 2SMR models. We uncovered shared and non-shared genetic architectures underlying causal associations. Direct causal effects of WC and HC on PCOS were revealed by two multivariable MR models containing exclusively the anthropometric markers of central obesity. Other multivariable MR models containing anthropometric markers of both central- and general obesity showed no direct causal effects on PCOS.ConclusionsBoth and general- and central obesity yield total causal effects on PCOS. Findings also indicated potential direct causal effects of normal weight-central obesity and more complex causal mechanisms when both central- and general obesity are present. Results underscore the importance of addressing both central- and general obesity for optimizing PCOS care.

Abstract Nano-structured metasurfaces have to be tailored from artificial atoms that act as toroidal emitters, giving rise to a new form of light long predicted: “flying doughnuts” as propagating spatial-temporal electromagnetic toroidal pulses in both the visible and THz regimes.

Background : Systematic reviews underpin clinical practice and policies that guide healthcare decisions. A core component of many systematic reviews is meta-analysis, which is a statistical synthesis of results across studies. Errors in the conduct and interpretation of meta-analysis can lead to incorrect conclusions regarding the benefits and harms of interventions; and studies have shown that these errors are common. Enabling peer reviewers to better detect errors in meta-analysis through the use of a checklist provides an opportunity for these errors to be rectified before publication. To our knowledge, no such checklist exists. Objective : To develop and evaluate a checklist to detect errors in pairwise meta-analyses in systematic reviews of interventions. Methods : We will undertake a four-step process to develop the checklist. First, we will undertake a systematic review of studies that have evaluated errors in the conduct and interpretation of meta-analysis to generate a bank of items to consider for the checklist. Second, we will undertake a survey of systematic review methodologists and statisticians to seek their views on which items, of the bank of items generated in step 1, are most important to include in the checklist. Third, we will hold a virtual meeting to agree upon which items to include in the checklist. Fourth, before finalising the checklist, we will pilot with editors and peer reviewers of journals. Conclusion : The developed checklist is intended to help journal editors and peer reviewers identify errors in the application and interpretation of meta-analyses in systematic reviews. Fewer errors in the conduct and improved interpretation will lead to more accurate review findings and conclusions to inform clinical practice.

Background: The intense interactions between people, animals and environmental systems in urban informal settlements compromise human and environmental health. Inadequate water and sanitation services, compounded by exposure to flooding and climate change risks, expose inhabitants to environmental contamination causing poor health and wellbeing and degrading ecosystems. However, the exact nature and full scope of risks and exposure pathways between human health and the environment in informal settlements are uncertain. Existing models are limited to microbiological linkages related to faecal-oral exposures at the individual level, and do not account for a broader range of human-environmental variables and interactions that affect population health and wellbeing. Methods: We undertook a 12-month health and environmental assessment in 12 flood-prone informal settlements in Makassar, Indonesia. We obtained caregiver-reported health data, anthropometric measurements, stool and blood samples from children

Objective Machine learning involves the use of algorithms without explicit instructions. Of late, machine learning models have been widely applied for the prediction of type 2 diabetes. However, no evidence synthesis of the performance of these prediction models of type 2 diabetes is available. We aim to identify machine learning prediction models for type 2 diabetes in clinical and community care settings and determine their predictive performance. Methods The systematic review of English language machine learning predictive modeling studies in 12 databases will be conducted. Studies predicting type 2 diabetes in predefined clinical or community settings are eligible. Standard CHARMS and TRIPOD guidelines will guide data extraction. Methodological quality will be assessed using a predefined risk of bias assessment tool. The extent of validation will be categorized by Reilly–Evans levels. Primary outcomes include model performance metrics of discrimination ability, calibration, and classification accuracy. Secondary outcomes include candidate predictors, algorithms used, level of validation, and intended use of models. The random-effects meta-analysis of c-indices will be performed to evaluate discrimination abilities. The c-indices will be pooled per prediction model, per model type, and per algorithm. Publication bias will be assessed through funnel plots and regression tests. Sensitivity analysis will be conducted to estimate the effects of study quality and missing data on primary outcome. The sources of heterogeneity will be assessed through meta-regression. Subgroup analyses will be performed for primary outcomes. Ethics and dissemination No ethics approval is required, as no primary or personal data are collected. Findings will be disseminated through scientific sessions and peer-reviewed journals. PROSPERO registration number CRD42019130886

Introduction Haemorrhage causes most preventable prehospital trauma deaths and about a third of in-hospital trauma deaths. Tranexamic acid (TXA), administered soon after hospital arrival in certain trauma systems, is an effective therapy in preventing or managing acute traumatic coagulopathy. However, delayed administration of TXA appears to be ineffective or harmful. The effectiveness of prehospital TXA, incidence of thrombotic complications, benefit versus risk in advanced trauma systems and the mechanism of benefit remain uncertain.Methods and analysis The Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH-Trauma study) is comparing TXA, initiated prehospital and continued in hospital over 8 hours, with placebo in patients with severe trauma at risk of acute traumatic coagulopathy. We present the trial protocol and an overview of the statistical analysis plan. There will be 1316 patients recruited by prehospital clinicians in Australia, New Zealand and Germany. The primary outcome will be the eight-level Glasgow Outcome Scale Extended (GOSE) at 6 months after injury, dichotomised to favourable (GOSE 5–8) and unfavourable (GOSE 1–4) outcomes, analysed using an intention-to-treat (ITT) approach. Secondary outcomes will include mortality at hospital discharge and at 6 months, blood product usage, quality of life and the incidence of predefined adverse events.Ethics and dissemination The study was approved by The Alfred Hospital Research and Ethics Committee in Victoria and also approved in New South Wales, Queensland, South Australia, Tasmania and the Northern Territory. In New Zealand, Northern A Health and Disability Ethics Committee provided approval. In Germany, Witten/Herdecke University has provided ethics approval. The PATCH-Trauma study aims to provide definitive evidence of the effectiveness of prehospital TXA, when used in conjunction with current advanced trauma care, in improving outcomes after severe injury.Trial registration number NCT02187120.

Abstract Orbital angular momentum interactions at the nanoscale have remained elusive because the phase structure becomes unresolved. Now researchers have shown how to overcome this with tightly focused beams, demonstrating a record-high six-dimensional encoding in an ultra-dense nanoscale volume.

ObjectivesUsing a nationally-representative, cross-sectional cohort, we examined nutritional markers of undiagnosed type 2 diabetes in adults via machine learning.MethodsA total of 16429 men and non-pregnant women ≥ 20 years of age were analysed from five consecutive cycles of the National Health and Nutrition Examination Survey. Cohorts from years 2013-2016 (n = 6673) was used for external validation. Undiagnosed type 2 diabetes was determined by a negative response to the question "Have you ever been told by a doctor that you have diabetes?" and a positive glycaemic response to one or more of the three diagnostic tests (HbA1c > 6.4% or FPG >125 mg/dl or 2-hr post-OGTT glucose > 200mg/dl). Following comprehensive literature search, 114 potential nutritional markers were modelled with 13 behavioural and 12 socio-economic variables. We tested three machine learning algorithms on original and resampled training datasets built using three resampling methods. From this, the derived 12 predictive models were validated on internal- and external validation cohorts. Magnitudes of associations were gauged through odds ratios in logistic models and variable importance in others. Models were benchmarked against the ADA diabetes risk test.ResultsThe prevalence of undiagnosed type 2 diabetes was 5.26%. Four best-performing models (AUROC range: 74.9%-75.7%) classified 39 markers of undiagnosed type 2 diabetes; 28 via one or more of the three best-performing non-linear/ensemble models and 11 uniquely by the logistic model. They comprised 14 nutrient-based, 12 anthropometry-based, 9 socio-behavioural, and 4 diet-associated markers. AUROC of all models were on a par with ADA diabetes risk test on both internal and external validation cohorts (p>0.05).ConclusionsModels performed comparably to the chosen benchmark. Novel behavioural markers such as the number of meals not prepared from home were revealed. This approach may be useful in nutritional epidemiology to unravel new associations with type 2 diabetes.

Background: Dietary guidelines should be informed by systematic reviews (SRs) of the available scientific evidence. However, if the SRs that underpin dietary guidelines are flawed in their design, conduct or reporting, the recommendations contained therein may be misleading or harmful. To date there has been little empirical investigation of bias due to selective inclusion of results, and bias due to missing results, in SRs of food/diet-outcome relationships. Objectives: To explore in SRs with meta-analyses of the association between food/diet and health-related outcomes: (i) whether systematic reviewers selectively included study effect estimates in meta-analyses when multiple effect estimates were available; (ii) what impact selective inclusion of study effect estimates may have on meta-analytic effects, and; (iii) the risk of bias due to missing results (publication bias and selective non-reporting bias) in meta-analyses. Methods: We will systematically search for SRs with meta-analysis of the association between food/diet and health-related outcomes in a generally healthy population, published between January 2018 and June 2019. We will randomly sort titles and abstracts and screen them until we identify 50 eligible SRs. The first reported meta-analysis of a binary or continuous outcome in each SR (the ‘index meta-analysis’) will be evaluated. We will extract from study reports all study effect estimates that were eligible for inclusion in the index meta-analyses (e.g. from multiple instruments and time points) and will quantify and test for evidence of selective inclusion of results. We will also assess the risk of bias due to missing results in the index meta-analyses using a new tool (ROB-ME). Ethics and dissemination: Ethics approval is not required because information will only be extracted from published studies. Dissemination of the results will be through peer-reviewed publications and presentations at conferences. We will make all data collected from this study publicly available via the Open Science Framework.

Orbital angular momentum (OAM) beams with topological charge ℓ are commonly generated and detected by modulating an incoming field with an azimuthal phase profile of the form exp(iℓϕ) by a variety of approaches. This results in unwanted radial modes and reduced power in the desired OAM mode. Here, we show how to enhance the modal purity in the creation and detection of classical OAM beams and in the quantum detection of OAM photons. Classically, we combine holographic and metasurface control to produce high purity OAM modes and show how to detect them with high efficiency, extending the demonstration to the quantum realm with spatial light modulators. We demonstrate ultra-high purity OAM modes in orders as high as ℓ = 100 and a doubling of dimensionality in the quantum OAM spectrum from a spontaneous parametric downconversion source. Our work offers a simple route to increase the channel capacity in classical and quantum communication using OAM modes as a basis.

Mi’kmaq Elder Albert Marshall coined “Two-Eyed Seeing” in 2004, an Indigenous concept that emphasizes integrating the strengths of multiple perspectives to address complex challenges in ways that benefit all. In 2011, Two-Eyed Seeing became a policy of the Canadian Institutes of Health Research (CIHR)–Institute of Aboriginal Peoples’ Health, as a part of its 5-year plan, and in 2012, CIHR funding was directed toward supporting efforts that apply the concept of Two-Eyed Seeing to research. However, little is known about how Two-Eyed Seeing has been operationalized in research. To address this ambiguity, a scoping review was conducted to map the key concepts involved when researchers intend to follow Two-Eyed Seeing guiding principles to study Indigenous health topics. Three research questions guided this scoping review: (1) What are the general characteristics (e.g., location of study, health topic studied) of primary research that has attempted to apply Two-Eyed Seeing when studying Indigenous health topics? (2) How did researchers operationalize the concept of Two-Eyed Seeing when they applied it to primary studies regarding Indigenous health topics? and (3) What process-related elements were present in Two-Eyed Seeing studies that accomplished their objectives? The results of this scoping review indicate there is an increasing trend in Two-Eyed Seeing–related peer-reviewed publications since its formal introduction by Mi’kmaq Elder Albert Marshall. The selected Two-Eyed Seeing–related projects were predominately conducted in Canada and published between 2011 and 2019. Projects predominately incorporated a community-based (participatory) research approach and qualitative/Indigenous methods, and six core process–related themes/elements were identified: (i) power was shared, (ii) culturally safe spaces were fostered, (iii) institutional and community ethics were followed, (iv) research projects were transformative, (v) rigor was maintained, and (vi) the structure of Western academia and traditional policy decision-making processes provided challenges for research teams and community partners, respectively.

Vectorial forms of structured light that are non-separable in their spatial and polarisation degrees of freedom have become topical of late, with an extensive toolkit for their creation and control. In contrast, the toolkit for quantifying their non-separability, the inhomogeneity of the polarisation structure, is less developed and in some cases fails altogether. To overcome this, here we introduce a new measure for vectorial light, which we demonstrate both theoretically and experimentally. We consider the general case where the local polarisation homogeneity can vary spatially across the field, from scalar to vector, a condition that can arise naturally if the composite scalar fields are path separable during propagation, leading to spatially disjoint vectorial light. We show how the new measure correctly accounts for the local path-like separability of the individual scalar beams, which can have varying degrees of disjointness, even though the global vectorial field remains intact. Our work attempts to address a pressing issue in the analysis of such complex light fields, and raises important questions on spatial coherence in the context of vectorially polarised light.

Abstract Background Knee osteoarthritis (OA) causes substantial pain, physical dysfunction and impaired quality of life. There is no cure for knee OA, and for some people, the disease may involve progressive symptomatic and structural deterioration over time. Platelet-rich plasma (PRP) is a therapeutic agent that aims to address underlying biological processes responsible for OA pathogenesis. As such, it has the potential to improve both symptoms and joint structure. The aim of this clinical trial is to determine whether a series of injections of PRP into the knee joint will lead to a significantly greater reduction in knee pain, and less loss of medial tibial cartilage volume over 12 months when compared to a series of placebo saline injections in people with knee OA. Methods This will be a two-group, superiority, randomised, participant-, interventionist- and assessor-blinded, placebo-controlled trial. Two hundred and eighty-eight participants aged over 50 years with painful knee OA and mild to moderate structural change on x-ray (Kellgren and Lawrence grade 2 and 3) will be randomly allocated to receive either three PRP injections or three normal saline injections into the knee joint at weekly intervals. The primary outcomes will be 12-month change in average overall knee pain severity (numeric rating scale) and medial tibial cartilage volume (magnetic resonance imaging (MRI)). Secondary outcomes include additional measures of knee pain and other symptoms, function in daily living and sport and recreation, quality of life, participant-perceived global ratings of change, and other MRI structural outcomes including meniscal and cartilage morphology, synovitis, effusion, bone marrow lesions and cartilage defects. A range of additional measures will be recorded, and a separate health economic evaluation will be performed. Discussion The findings from this study will help determine whether PRP improves both clinical and structural knee OA outcomes over 12 months when compared to a series of placebo saline injections. Trial registration Australian New Zealand Clinical Trials Registry reference: ACTRN12617000853347. Prospectively registered 9th of June 2017.

Abstract Background The Prophylactic hypOthermia to Lessen trAumatic bRain injury-Randomised Controlled Trial (POLAR-RCT) will evaluate whether early and sustained prophylactic hypothermia delivered to patients with severe traumatic brain injury improves patient-centred outcomes. Methods The POLAR-RCT is a multicentre, randomised, parallel group, phase III trial of early, prophylactic cooling in critically ill patients with severe traumatic brain injury, conducted in Australia, New Zealand, France, Switzerland, Saudi Arabia and Qatar. A total of 511 patients aged 18–60 years have been enrolled with severe acute traumatic brain injury. The trial intervention of early and sustained prophylactic hypothermia to 33 °C for 72 h will be compared to standard normothermia maintained at a core temperature of 37 °C. The primary outcome is the proportion of favourable neurological outcomes, comprising good recovery or moderate disability, observed at six months following randomisation utilising a midpoint dichotomisation of the Extended Glasgow Outcome Scale (GOSE). Secondary outcomes, also assessed at six months following randomisation, include the probability of an equal or greater GOSE level, mortality, the proportions of patients with haemorrhage or infection, as well as assessment of quality of life and health economic outcomes. The planned sample size will allow 80% power to detect a 30% relative risk increase from 50% to 65% (equivalent to a 15% absolute risk increase) in favourable neurological outcome at a two-sided alpha of 0.05. Discussion Consistent with international guidelines, a detailed and prospective analysis plan has been developed for the POLAR-RCT. This plan specifies the statistical models for evaluation of primary and secondary outcomes, as well as defining covariates for adjusted analyses and methods for exploratory analyses. Application of this statistical analysis plan to the forthcoming POLAR-RCT trial will facilitate unbiased analyses of these important clinical data. Trial registration ClinicalTrials.gov, NCT00987688 (first posted 1 October 2009); Australian New Zealand Clinical Trials Registry, ACTRN12609000764235. Registered on 3 September 2009.

Background: Dietary guidelines should be informed by systematic reviews (SRs) of the available scientific evidence. However, if the SRs that underpin dietary guidelines are flawed in their design, conduct or reporting, the recommendations contained therein may be misleading or harmful. To date there has been little empirical investigation of bias due to selective inclusion of results, and bias due to missing results, in SRs of food/diet-outcome relationships. Objectives: To explore in SRs with meta-analyses of the association between food/diet and health-related outcomes: (i) whether systematic reviewers selectively included study effect estimates in meta-analyses when multiple effect estimates were available; (ii) what impact selective inclusion of study effect estimates may have on meta-analytic effects, and; (iii) the risk of bias due to missing results (publication bias and selective non-reporting bias) in meta-analyses. Methods: We will systematically search for SRs with meta-analysis of the association between food/diet and health-related outcomes in a generally healthy population, published between January 2018 and June 2019. We will randomly sort titles and abstracts and screen them until we identify 50 eligible SRs. The first reported meta-analysis of a binary or continuous outcome in each SR (the ‘index meta-analysis’) will be evaluated. We will extract from study reports all study effect estimates that were eligible for inclusion in the index meta-analyses (e.g. from multiple instruments and time points) and will quantify and test for evidence of selective inclusion of results. We will also assess the risk of bias due to missing results in the index meta-analyses using a new tool (ROB-ME). Ethics and dissemination: Ethics approval is not required because information will only be extracted from published studies. Dissemination of the results will be through peer-reviewed publications and presentations at conferences. We will make all data collected from this study publicly available via the Open Science Framework.