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Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Abstract Background Glioblastoma (GBM) is the most common adult malignant brain tumour, with an incidence of 5 per 100,000 per year in England. Patients with tumours showing O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation represent around 40% of newly diagnosed GBM. Relapse/tumour recurrence is inevitable. There is no agreed standard treatment for patients with GBM, therefore, it is aimed at delaying further tumour progression and maintaining health-related quality of life (HRQoL). Limited clinical trial data exist using cannabinoids in combination with temozolomide (TMZ) in this setting, but early phase data demonstrate prolonged overall survival compared to TMZ alone, with few additional side effects. Jazz Pharmaceuticals (previously GW Pharma Ltd.) have developed nabiximols (trade name Sativex®), an oromucosal spray containing a blend of cannabis plant extracts, that we aim to assess for preliminary efficacy in patients with recurrent GBM. Methods ARISTOCRAT is a phase II, multi-centre, double-blind, placebo-controlled, randomised trial to assess cannabinoids in patients with recurrent MGMT methylated GBM who are suitable for treatment with TMZ. Patients who have relapsed ≥ 3 months after completion of initial first-line treatment will be randomised 2:1 to receive either nabiximols or placebo in combination with TMZ. The primary outcome is overall survival time defined as the time in whole days from the date of randomisation to the date of death from any cause. Secondary outcomes include overall survival at 12 months, progression-free survival time, HRQoL (using patient reported outcomes from QLQ-C30, QLQ-BN20 and EQ-5D-5L questionnaires), and adverse events. Discussion Patients with recurrent MGMT promoter methylated GBM represent a relatively good prognosis sub-group of patients with GBM. However, their median survival remains poor and, therefore, more effective treatments are needed. The phase II design of this trial was chosen, rather than phase III, due to the lack of data currently available on cannabinoid efficacy in this setting. A randomised, double-blind, placebo-controlled trial will ensure an unbiased robust evaluation of the treatment and will allow potential expansion of recruitment into a phase III trial should the emerging phase II results warrant this development. Trial registration ISRCTN: 11460478. ClinicalTrials.Gov: NCT05629702.

Abstract Background In this article we describe the methodology of the time-to-event continual reassessment method in the presence of partial orders (PO-TITE-CRM) and the process of implementing this trial design into a phase I trial in head and neck cancer called ADePT-DDR. The ADePT-DDR trial aims to find the maximum tolerated dose of an ATR inhibitor given in conjunction with radiotherapy in patients with head and neck squamous cell carcinoma. Methods The PO-TITE-CRM is a phase I trial design that builds upon the time-to-event continual reassessment method (TITE-CRM) to allow for the presence of partial ordering of doses. Partial orders occur in the case where the monotonicity assumption does not hold and the ordering of doses in terms of toxicity is not fully known. Results We arrived at a parameterisation of the design which performed well over a range of scenarios. Results from simulations were used iteratively to determine the best parameterisation of the design and we present the final set of simulations. We provide details on the methodology as well as insight into how it is applied to the trial. Conclusions Whilst being a very efficient design we highlight some of the difficulties and challenges that come with implementing such a design. As the issue of partial ordering may become more frequent due to the increasing investigations of combination therapies we believe this account will be beneficial to those wishing to implement a design with partial orders. Trial registration ADePT-DDR was added to the European Clinical Trials Database (EudraCT number: 2020-001034-35) on 2020-08-07.

Background: Acute respiratory infections (ARIs) are a significant public health concern in India, accounting for 15–30% of all fatalities among children younger than 5 years. Aims and Objectives: This study estimated the prevalence of ARI and its association with sociodemographic variables and housing conditions in under-five children in rural Jhansi, Bundelkhand region. Materials and Methods: This community-based cross-sectional analytical study was conducted in the selected Anganwadi Centers in Badagaon Block, Jhansi. Data for sociodemographic factors and housing conditions were collected by interviewing parents or caretakers of under-five children using a semi-structured predesigned and pretested pro forma during a house-to-house visit. The sociodemographic factors considered were the educational status of the parents, occupation of the father, religion of the child, socioeconomic class of the family, age of the child, type of family, and sex of the child. The parameters of housing conditions evaluated were overcrowding, ventilation type of chulha, and type of house. Results: The overall prevalence of ARI was found to be 48.88%. Significant sociodemographic factors for ARIs have been the educational level of the mother (χ2=18.69, P

Abstract In optic neuropathies, including glaucoma, retinal ganglion cells (RGCs) die. Cell transplantation and endogenous regeneration offer strategies for retinal repair, however, developmental programs required for this to succeed are incompletely understood. To address this, we explored cellular reprogramming with transcription factor (TF) regulators of RGC development which were integrated into human pluripotent stem cells (PSCs) as inducible gene cassettes. When the pioneer factor NEUROG2 was combined with RGC-expressed TFs (ATOH7, ISL1, and POU4F2) some conversion was observed and when pre-patterned by BMP inhibition, RGC-like induced neurons (RGC-iNs) were generated with high efficiency in just under a week. These exhibited transcriptional profiles that were reminiscent of RGCs and exhibited electrophysiological properties, including AMPA-mediated synaptic transmission. Additionally, we demonstrated that small molecule inhibitors of DLK/LZK and GCK-IV can block neuronal death in two pharmacological axon injury models. Combining developmental patterning with RGC-specific TFs thus provided valuable insight into strategies for cell replacement and neuroprotection.

Abstract. Background. To evaluate the predictive values of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2), prostate-specific antigen (PSA) level, PSA density (PSAD), digital rectal examination findings, and prostate volume, individually and in combination, for the detection of prostate cancer (PCa) in biopsy-naive patients. Methods. We retrospectively analyzed 630 patients who underwent transrectal systematic prostate biopsy following prostate multiparametric magnetic resonance imaging. A standard 12-core biopsy procedure was performed. Univariate and multivariate analyses were performed to determine the significant predictors of clinically significant cancer but not PCa. Results. The median age, PSA level, and PSAD were 70 years, 8.6 ng/mL, and 0.18 ng/mL/mL, respectively. A total of 374 (59.4%) of 630 patients were biopsy-positive for PCa, and 241 (64.4%) of 374 were diagnosed with clinically significant PCa (csPCa). The PI-RADS v2 score and PSAD were independent predictors of PCa and csPCa. The PI-RADS v2 score of 5 regardless of the PSAD value, or PI-RADS v2 score of 4 plus a PSAD of

The differential transmission of COVID-19 depending on the socio-economic status of a neighborhood is well established. For example, several studies have shown that COVID-19 transmission was higher in poorer and denser neighborhoods than in wealthier ones. However, what is less well known is how this varied rate of transmission interacted with established health measures, i.e., face masks and lockdowns, in the context of developing countries to reduce pandemic cases and hence resulted in fewer deaths. This study uses an Agent-Based Model (ABM) simulation to examine the context and impacts of COVID-19 mitigation efforts (i.e., lockdowns combined with masks) on the transmission of COVID-19 across a single neighborhood in Ahmedabad, a city in the state of Gujarat, India. The model is parameterized using real-world population data, which allows us to simulate the spread of COVID-19 to find conditions that most closely match the realities of COVID-19 in the spring of 2020. Consequently, the simulation can be used to understand the impact of nation-wide lockdown on the spread of COVID cases across Ahmedabad as a function of housing density. Thus, invaluable insight into the effectiveness of a lockdown as a mitigation measure can be derived. Further information about how the effectiveness of the lockdown varied by neighborhood, as well as other factors that impacted it, can be ascertained.

Category: Hindfoot; Ankle Introduction/Purpose: Insertional Achilles Tendinopathy (IAT) is a degenerative process at the insertion of Achilles tendon onto the calcaneal tuberosity that often coexists with retrocalcaneal bursitis and Haglund’s deformity. The Zadek osteotomy, a dorsal closing wedge osteotomy of the calcaneus, has been described as a treatment option in patients with IAT that have failed conservative management. The aim of this study was to evaluate the clinical outcomes and the complications of the Zadek for the management of IAT. Methods: PubMed, EMBASE and Cochrane Central Register of Controlled Trails (CENTRAL) were searched for all studies to November 2022. PRISMA guidelines were followed. The overall estimates of effect were presented as Weighted Mean Difference (WMD) and 95% confidence intervals (CIs). Meta-analysis was conducted using the Review Manager Software (RevMan, Version 5.4). Results: Ten studies with 232 patients were included. The AOFAS (American Orthopaedic Foot and Ankle Society) Ankle- Hindfoot Score and the VISA-A score (Victorian Institute of Sports of Australia-Achilles score) were significantly improved after the Zadek osteotomy (p < 0.00001). Pain levels were also significantly reduced (p < 0.00001). There were a total of 22 complications reported in the included studies and they were all considered minor. The most common complications were superficial wound infection and sural nerve paraesthesia. Conclusion: The Zadek osteotomy is a safe and effective procedure for patients with IAT. The osteotomy improves pain levels and functions and is associated only with minor complications and a low complication rate. There are no well-designed randomized controlled trials in the literature assessing the outcomes of a Zadek osteotomy against alternate surgical treatments and future research should focus on this.

Abstract. Urolithiasis is the most common cause of nonobstetric abdominal pain, resulting in 1.7 admissions per 1000 deliveries. Urolithiasis most commonly occurs in the second and third trimesters, with an incidence between 1:125 and 1:2000. Acute urinary system obstructions are challenging to manage in obstetric patients because they contribute to physiological and anatomical changes that result in pathological outcomes. The restricted use of computed tomography in diagnosing and managing urolithiasis is particularly challenging. In addition, a prompt diagnosis is required because the presence of renal calculi during pregnancy increases the risk of fulminating sepsis and preterm delivery. Affected pregnancies are conservatively managed; however, 1 in 4 requires surgical intervention. Indications for surgical interventions are complex and range from nephrostomy insertion to empirical stent placement or ureteroscopy. Therefore, a multidisciplinary approach is required to optimize patient care. The diagnosis and management of urolithiasis in pregnancy are complex. We reviewed the role, safety, advantages and disadvantages of diagnostic tests and treatment used to manage acute urinary obstructions in pregnancy.

Introduction The effects of COVID-19 infection persist beyond the active phase. Comprehensive description and analysis of the post COVID sequelae in various population groups are critical to minimise the long-term morbidity and mortality associated with COVID-19. This analysis was conducted with an objective to estimate the frequency of post COVID sequelae and subsequently, design a framework for holistic management of post COVID morbidities.Methods Follow-up data collected as part of a registry-based observational study in 31 hospitals across India since September 2020–October 2022 were used for analysis. All consenting hospitalised patients with COVID-19 are telephonically followed up for up to 1 year post-discharge, using a prestructured form focused on symptom reporting.Results Dyspnoea, fatigue and mental health issues were reported among 18.6%, 10.5% and 9.3% of the 8042 participants at first follow-up of 30–60 days post-discharge, respectively, which reduced to 11.9%, 6.6% and 9%, respectively, at 1-year follow-up in 2192 participants. Patients who died within 90 days post-discharge were significantly older (adjusted OR (aOR): 1.02, 95% CI: 1.01, 1.03), with at least one comorbidity (aOR: 1.76, 95% CI: 1.31, 2.35), and a higher proportion had required intensive care unit admission during the initial hospitalisation due to COVID-19 (aOR: 1.49, 95% CI: 1.08, 2.06) and were discharged at WHO ordinal scale 6–7 (aOR: 49.13 95% CI: 25.43, 94.92). Anti-SARS-CoV-2 vaccination (at least one dose) was protective against such post-discharge mortality (aOR: 0.19, 95% CI: 0.01, 0.03).Conclusion Hospitalised patients with COVID-19 experience a variety of long-term sequelae after discharge from hospitals which persists although in reduced proportions until 12 months post-discharge. Developing a holistic management framework with engagement of care outreach workers as well as teleconsultation is a way forward in effective management of post COVID morbidities as well as reducing mortality.

Brushless direct current motors have more attractive features, making them a promising solution for electric vehicle applications. A 1 kW, 510 rpm, 24-slots and 8-pole inner runner type surface permanent magnet mounted radial flux brushless DC motor with seven different permanent magnet pole shape rotor is investigated. Motors with different permanent magnet shape rotors were designed, and finite element modelling and simulation were carried out. For performance comparison, the initial design with a radial-type pole shape was regarded as a reference design. Cogging torque is detrimental to the overall performance of the motor, typically in low-speed applications like electric vehicles. The primary aim of this paper is to reduce the cogging torque & study its effect on the overall performance of the motor and minimize torque ripples with reduced permanent magnet requirements. The proposed designs are analyzed in terms of cogging torque, flux density, torque, efficiency, flux linkage and back-EMF. The comparative analysis shows that the motor with bump-shaped permanent magnet rotor poles has better performance than the others.

This paper embodies the design and development of a compact Coplanar Waveguide (CPW) fed connected ground Multiple- Input-Multiple-Output (MIMO) antennas operating in the sub-millimeter-wave 5G New Radio (NR) n257/n258/n261 bands. The planar geometry leads to a small and compact structure while achieving a wide operating bandwidth, high gain, and better radiation efficiency. The top surface of the antenna comprises a modified CPW in the form of two circular structures that feeds the centrally slotted circular patch. The single antenna structure is arranged in a rotational orthogonal manner forming a 4-port structure. The ground plane on the bottom of a 4-port structure is connected using a circular ring which is carefully optimized for achieving isolation levels>20 dB across the band of interest. The sub-mm-wave resonating 4-port antenna achieves a compact size of 24 × 24 mm2, a wide bandwidth of 24.8–44.45 GHz (79.35%), the maximum gain of 8.6dBi, and minimum efficiency of 85% across the bands of interest. The proposed antenna element is fabricated over Rogers 5880 substrate and experimental tests are carried out, where a good correlation between the scattering parameters, transmission parameters, gain, and MIMO diversity performance is achieved that makes the antenna a potential candidate for its application in sub-millimeter wave 5G applications.

Auckland's road safety performance deteriorated significantly with death and serious injury crashes increasing by more than 70% between 2014-2017 compared to the previous five years. A fifth of all pedestrian related crashes in Auckland occurred at existing zebra crossings. In response, the Mass Action Pedestrian Improvement Programme (MAPI) delivered 37 upgrades of existing at grade crossings to raised zebra crossings over 2018/19 financial year and since this time, Auckland Transport have upgraded more than 100 crossings across the network. This paper discusses the research and evaluation that were undertaken to inform the design and implementation of MAPI and to determine safety outcomes and impacts. Key learnings from the programme and the challenge of balancing safety benefits, community acceptance, and the efficient operation of the network, are discussed.

This paper presents the application of higher-grade magnetic material for performance improvement of interior permanent magnet synchronous motors (IPMSM) for high-speed applications. The efficiency and weight of the motor are important performance parameters for high-speed applications. Efficiency improvement with simultaneous weight reduction is the key design issue for many specific applications. The main contribution of this work is to explore the possibility of using high-grade magnetic material for efficiency improvement with a simultaneous weight reduction of IPMSM motors. Three different standard rating motors were designed with the usual M19 material, and their performance was estimated. Finite element modelling and simulation was carried out to validate the initial design. For performance comparison, initial designs were regarded as reference designs. Design improvement was carried out with the application of high-grade magnetic material Hiperco 50A and its influence on the performance of IPMSM motors was analyzed. Three different standard ratings motors were considered in this work to analyze the effect of material in a wide range. Improved design was also validated with finite element modelling and simulation. It was observed that the efficiency is effectively improved with weight reduction using Hiperco 50A material in all three standard-rating IPMSM motors.

Introduction: Psoriasis (kitibha) is characterized by chronic inflammation and epidermal hyperplasia where mast cells and tryptase are activated with related form of cytokines. Cipadessa baccifera (Roth.) Miq. (Meliaceae family) is an ethnomedicinal plant reported for its anti-psoriatic tribal claim. In the present study, in silico docking study was planned for proven clinical use of C. baccifera in psoriasis with identified phytoconstituents. Methods: Eight identified well-known phytochemicals from the leaf of C. baccifera were used. The molecular docking studies were performed using iGEMDOCK2.1. Drug likeness of the compounds was predicted using Swiss ADME while in silico toxicity studies were performed using ProTox-II online tool. Results: All of retrieved eight phytoconstituents of C. baccifera possesses drug likeness properties. Phytoconstituents are nontoxic in nature and showing bioavailability, having significant inhibitory activities on validated anti-psoriatic targeted proteins, 2ZEB (Human Mast Cell Tryptase) and 2AOT (Histamine methyltransferase). Conclusion: The results of present study suggest the potential clinical role of C. baccifera in psoriatic patients and thus, proved the traditional claim through in silico docking study.

Background While there are many epidemiologic studies of Asian immigrants to the West and risk of inflammatory bowel disease (IBD), the phenotype and lifestyle of Asian patients, particularly children, with IBD are not well described. In this study, we describe lifestyle practices, such as dietary pattern, as well as disease phenotype in Asian American children with IBD. Methods We reviewed the records of children with IBD, ages 0 to 21 years old, and race identified as Asian, Indian, or Pacific Islander. Patients who received outpatient IBD care at our center between January 2013 and January 2020 were included. We excluded patients who were international second opinions, who did not have a definitive diagnosis of IBD, and in whom a diagnosis of IBD was made after 18 years of age. A survey, including a food frequency questionnaire adapted from NHANES DSQ with modifications to include culturally appropriate food elements, was designed and conducted within this cohort to assess for dietary patterns. Results Asian patients in our cohort have similar phenotypes as non-Asians with few distinctive differences. There was a Crohn’s disease and male predominance similar with non-Asians. However, there was a high rate of proctitis in ulcerative colitis in Asian patients. Asian patients reported a typical dietary pattern that reflects a Westernized pattern rather than a traditional pattern. Despite a similar dietary pattern, there was a high rate of 25-OH Vitamin D deficiency (44%) and insufficiency (40%). Conclusions This single center study showed that the phenotype of Asian children with IBD in the U.S. is similar with that of non-Asian with a few distinct differences. The Asian children in our cohort reported following a Westernized dietary pattern and lifestyle. However, there was a high rate of Vitamin D deficiency surrounding diagnosis, suggesting a need for vigilant monitoring.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

This research work focused on simulating different fracture modes in the high-stress concentrated region of an advanced SiC/SiC CMC component at the macroscopic scale in consideration of increasing cost and time during experimental tests of CMCs. A hybrid of extended-finite-element-method (XFEM) and cohesive-zone-modeling (CZM) was utilized to predict mode-I and mode-II fracture behavior, respectively. The cohesive element (CE) layers were used as fiber-tow interfaces in the stress-concentrated region where mode-II failure was supposed to occur. The 1st crack initiation and its further propagation were found to be dependent on XFEM damage criteria, whereas delamination was observed at the damage-front CE layers. The simulated force-displacement relationships were compared with the experimental ones, where stiffness and serrations in the force-displacement curve corresponding to the delamination matched quite well. With concern to predicting the fracture behavior in a complex-shape component of SiC/SiC CMCs, XFEM with CZM methodology can be a reliable method in the near future.

Introduction Gliomas are the most common primary tumour of the central nervous system (CNS), with an estimated annual incidence of 6.6 per 100 000 individuals in the USA and around 14 deaths per day from brain tumours in the UK. The genomic and biological landscape of brain tumours has been increasingly defined and, since 2016, the WHO classification of tumours of the CNS incorporates molecular data, along with morphology, to define tumour subtypes more accurately. The Tessa Jowell BRAIN MATRIX Platform (TJBM) study aims to create a transformative clinical research infrastructure that leverages UK National Health Service resources to support research that is patient centric and attractive to both academic and commercial investors.Methods and analysis The TJBM study is a programme of work with the principal purpose to improve the knowledge of glioma and treatment for patients with glioma. The programme includes a platform study and subsequent interventional clinical trials (as separate protocols). The platform study described here is the backbone data-repository of disease, treatment and outcome data from clinical, imaging and pathology data being collected in patients with glioma from secondary care hospitals. The primary outcome measure of the platform is time from biopsy to integrated histological–molecular diagnosis using whole-genome sequencing and epigenomic classification. Secondary outcome measures include those that are process centred, patient centred and framework based. Target recruitment for the study is 1000 patients with interim analyses at 100 and 500 patients.Ethics and dissemination The study will be performed in accordance with the recommendations guiding physicians in biomedical research involving human subjects, adopted by the 18th World Medical Association General Assembly, Helsinki, Finland and stated in the respective participating countries’ laws governing human research, and Good Clinical Practice. The protocol was initially approved on 18 February 2020 by West Midlands – Edgbaston Research Ethics Committee; the current protocol (v3.0) was approved on 15 June 2022. Participants will be required to provide written informed consent. A meeting will be held after the end of the study to allow discussion of the main results among the collaborators prior to publication. The results of this study will be disseminated through national and international presentations and peer-reviewed publications. Manuscripts will be prepared by the Study Management Group and authorship will be determined by mutual agreement.Trial registration number NCT04274283, 18-Feb-2020; ISRCTN14218060, 03-Feb-2020.

Kidney trade has been on the rise despite the domestic and international law enforcement aiming to protect the vulnerable population from potential exploitation. Regional hubs are emerging in several parts of the world including South Asia, Central America, the Middle East and East Asia. Kidney trade networks reported in these hot spots are often complex systems involving several players such as buyers, sellers and surgery countries operating across international borders so that they can bypass domestic laws in sellers and buyers’ countries. The exact patterns of the country networks are, however, largely unknown due to the lack of a systematic approach to collect the data. Most of the kidney trade information is currently available in the form of case studies, court materials and news articles or reports, and no comprehensive database exists at this time. The present study thus explored online newspaper scraping to systematically collect 10 419 news articles from 24 major English newspapers in South Asia (January 2016 to May 2019) and build transnational kidney trade networks at the country level. Additionally, this study applied text mining techniques to extract words from each news article and developed machine learning algorithms to identify kidney trade and non-kidney trade news articles. Our findings suggest that online newspaper scraping coupled with the machine learning method is a promising approach to compile such data, especially in the dire shortage of empirical data.

Lack of investment for magnetic resonance (MR) fusion systems is an obstacle to deliver targeted prostate biopsies within the prostate cancer diagnostic pathway. We developed a coordinate-based method to support cognitive targeted prostate biopsies and then performed an audit on cancer detection and the location of lesions. In each patient, the prostate is considered as two separate hemiprostates, and each hemiprostate is divided into 4 × 4 × 4 units. Each unit is therefore defined by a three-dimensional coordinate. We prospectively applied our coordinates approach to target 106 prostatic lesions in 93 men. Among 45 (of 106; 42.5%) lesions positive for cancer, 27 lesions (60.0%) harbored clinically significant disease. PSA density was significantly higher in patients with proven cancer (median: 0.264 ng ml−2) when compared to the noncancer group (median: 0.145 ng ml−2; P = 0.003, Wilcoxon rank-sum test). Lesions with Prostate Imaging-Reporting and Data System (PIRADS) score of 5 were found to have a cancer incidence of 65.2%, while PIRADS 4 and 3 lesions have a lower risk of cancer detection, as expected, at 37.3% and 31.3%, respectively. The probability of a lesion being cancerous in our series significantly decreases as we go from the “apex-to-base” dimension (odds ratio [OR]: 2.62, 95% confidence interval [CI]: 1.55–4.44, P = 0.00034). Our analysis also indicates that the probability of cancer decreases as the prostate volume increases (OR: 1.03, 95% CI: 1.01–1.05, P = 0.00327). Based on this feasibility study, the use of coordinates to guide cognitive targeted prostate biopsies warrants future validation study in additional centers.

Background: Ankle fracture fixation is one of the most commonly performed orthopaedic procedures. Although the results are generally favourable, complications are not uncommon, particularly in the case of surgical site infec- tions. These have considerable impact on both postoperative morbidity and healthcare costs. The purpose of this study was to determine the infection rate following ankle fracture fixation and elucidate variables in their causation. Methods: We retrospectively reviewed 50 consecutive patients who underwent open reduction and internal fixation of an ankle fracture. The study group consisted of 26 females and 24 males with an average age of 43 (Range 16-82) years. Results: Problems with superficial infections were noted in seven patients and deep infections in five. Of the latter, four patients underwent further surgery including two that had their metal work removed. With use of the Fisher’s exact test we determined that only smoking and a bimalleolar fracture pattern were significant variables, having p- values of 0.02 and 0.04 respectively. Conclusion: We conclude that smoker and/or patient with bimalleolar injury have are more at risk of developing surgical site infection and its implications on their functional recovery Following Open Reduction and Internal Fixa- tion of Ankle Fractures.

Abstract Background Robust diagnosis of dementia requires an understanding of the accuracy of the available diagnostic tests. Informant questionnaires are frequently used to assess for dementia in clinical practice. Recent systematic reviews have sought to establish the diagnostic test accuracy of various dementia informant screening tools. However, most reviews to date have focused on a single diagnostic tool and this does not address which tool is ‘best’. A key aim of the overview of systematic reviews is to present a disparate evidence base in a single, easy to access platform. Methods We will conduct an overview of systematic reviews in which we ‘review the systematic reviews’ of diagnostic test accuracy studies evaluating informant questionnaires for dementia. As an overview of systematic reviews of test accuracy is a relatively novel approach, we will use this review to explore methods for visual representation of complex data, for highlighting evidence gaps and for indirect comparative analyses. We will create a list of informant tools by consulting with dementia experts. We will search 6 databases (EMBASE (OVID); Health and Psychosocial Instruments (OVID); Medline (OVID); CINAHL (EBSCO); PSYCHinfo (EBSCO) and the PROSPERO registry of review protocols) to identify systematic reviews that describe the diagnostic test accuracy of informant questionnaires for dementia. We will assess review quality using the AMSTAR-2 (Assessment of Multiple Systematic Reviews) and assess reporting quality using PRISMA-DTA (Preferred Reporting Items for Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies) checklists. We will collate the identified reviews to create an ‘evidence map’ that highlights where evidence does and does not exist in relation to informant questionnaires. We will pool sensitivity and specificity data via meta-analysis to generate a diagnostic test accuracy summary statistic for each informant questionnaire. If data allow, we will perform a statistical comparison of the diagnostic test accuracy of each informant questionnaire using a network approach. Discussion Our overview of systematic reviews will provide a concise summary of the diagnostic test accuracy of informant tools and highlight areas where evidence is currently lacking in this regard. It will also apply network meta-analysis techniques to a new area.

Palmprints can be characterized by their texture and the patterns of that texture dominate in a vertical direction. Therefore, the energy of the coefficients in the transform domain is more concentrated in the vertical sideband. Using this idea, this paper proposes the characterization of the texture features of the palmprint using zero-crossing signatures based on the dyadic discrete wavelet transform (DWT) to effectively identify an individual. A zero-crossing signature of 4 x 256 was generated from the lower four resolution levels of dyadic DWT in the enrolment process and stored in the database to identify the person in recognition mode. Euclidean distance was determined to find the best fit for query palmprints zero-crossing signature from the dataset. The proposed algorithm was tested on the PolyU dataset containing 6000 multi-spectral images. The proposed algorithm achieved 96.27% accuracy with a lower recognition time of 0.76 seconds. ABSTRAK: Pengesan Tapak Tangan boleh dikategorikan berdasarkan ciri-ciri tekstur dan corak pada tekstur yang didominasi pada garis tegak. Oleh itu, pekali tenaga di kawasan transformasi adalah lebih penuh pada jalur-sisi menegak. Berdasarkan idea ini, cadangan kajian ini adalah berdasarkan ciri-ciri tekstur pada tapak tangan dan tanda pengenalan sifar-silang melalui transformasi gelombang kecil diadik yang diskret (DWT) bagi mengecam individu. Pada mod pengecaman, tanda pengenalan sifar-silang 4 x 256 yang terhasil daripada tahap diadik resolusi empat terendah DWT digunakan dalam proses kemasukan dan simpanan di pangkalan data bagi mengenal pasti individu. Jarak Euklidan yang terhasil turut digunakan bagi memperoleh padanan tapak tangan paling sesuai melalui tanda pengenalan sifar-silang dari set data. Algoritma yang dicadangkan ini diuji pada set data PolyU yang mengandungi 6000 imej pelbagai-spektrum. Algoritma yang dicadangkan ini berjaya mencapai ketepatan sebanyak 96.27% dengan durasi pengecaman berkurang sebanyak 0.76 saat.

BackgroundThe Covid-19 pandemic in the United Kingdom has seen two waves; the first starting in March 2020 and the second in late October 2020. It is not known whether outcomes for those admitted with severe Covid were different in the first and second waves.MethodsThe study population comprised all patients admitted to a 1,500-bed London Hospital Trust between March 2020 and March 2021, who tested positive for Covid-19 by PCR within 3-days of admissions. Primary outcome was death within 28-days of admission. Socio-demographics (age, sex, ethnicity), hypertension, diabetes, obesity, baseline physiological observations, CRP, neutrophil, chest x-ray abnormality, remdesivir and dexamethasone were incorporated as co-variates. Proportional subhazards models compared mortality risk between wave 1 and wave 2. Cox-proportional hazard model with propensity score adjustment were used to compare mortality in patients prescribed remdesivir and dexamethasone.ResultsThere were 3,949 COVID-19 admissions, 3,195 hospital discharges and 733 deaths. There were notable differences in age, ethnicity, comorbidities, and admission disease severity between wave 1 and wave 2. Twenty-eight-day mortality was higher during wave 1 (26.1% versus 13.1%). Mortality risk adjusted for co-variates was significantly lower in wave 2 compared to wave 1 [adjSHR 0.49 (0.37, 0.65) pConclusionThere has been substantial improvements in COVID-19 mortality in the second wave, even accounting for demographics, comorbidity, and disease severity. Neither dexamethasone nor remdesivir appeared to be key explanatory factors, although there may be unmeasured confounding present.

Category: Ankle; Hindfoot; Trauma Introduction/Purpose: Open talar dislocations with complete or partial extrusion of the talus are rare, high energy injuries associated with major complications including infection, avascular necrosis and post-traumatic arthritis. These are debilitating injuries with significant long-term effects including avascular necrosis and post traumatic arthritis. Functional outcome data in the literature is limited and predominantly consists of case reports and few single centre case series. Historically these injuries have been treated with talectomy and tibiocalcaneal arthrodesis, however there has been a subsequent trend towards debridement and reimplantation with preservation of the extruded talus. Our aim was to evaluate mid-term functional outcomes, assess complication profile and need for secondary surgery in a single-centre series of cases treated with reimplantation. Methods: All talar extrusion injuries presenting between January 2015 and January 2018 were identified from the trauma database search at our major trauma centre. Inclusion criteria was defined as open talar dislocations associated with either complete or partial extrusion of the talus. Case-note review was performed collecting baseline demographic data including age, gender, injury mechanism, associated injuries, Gustilo-Anderson grade, smoking and diabetes status, and method and timing of surgical management. Twelve patients were identified with a mean follow-up of 3 years (minimum 26 months). Primary outcome measure was functional outcome assessed using the Manchester-Oxford Foot Questionnaire (MOxFQ). Results for each of the three domains were converted to a 0-100 scale for comparison. Secondary outcomes included complication rate and all cause re- operation rates Results: Mean age was 37.8 years (17-74 years). Five patients (42%) had total talar extrusion without fracture and 7/12 (58%) sustained fracture-dislocation with partial talar extrusion. All were Gustilo-Anderson grade III. All underwent successful reimplantation with 8/12 (67%) treated with single stage surgery, and 4/12 (33%) in two stages. The mean MOxFQ scores for total talar extrusions versus partial talar extrusions with fracture were 79 (range 9-18) vs 41 (range 0-86) for walking domain, 65 (range 45-80) vs 42 (range 0-90) for pain domain, and 63 (range 38-75) vs 48 (range 19-51) for social domain. One patient (8%) developed avascular necrosis, 3/12 (25%) developed infection and 1/12 (8%) patient eventually required below knee amputation. One (8%) patient underwent secondary surgery fusion for post-traumatic arthritis. Conclusion: Our series demonstrates the serious ramifications of sustaining talar extrusions. Patients who sustain these injuries should expect persistent functional deficit and pain at mid-term follow-up. Functional outcomes are relatively poor. The data demonstrates a trend towards better functional outcomes in patients who have partial extrusion of the talar dome with associated fractures, compared to ligamentous total talar extrusion injuries. The incidence of avascular necrosis, deep infection and secondary surgery in our cohort supports reimplantation as an effective treatment strategy.

Category: Midfoot/Forefoot; Trauma Introduction/Purpose: Overwhelming demand for trauma services with increasing emergency department (ED) attendances, has increased pressure on fracture clinics in many units, with this demand exceeding capacity. Virtual fracture clinics (VFCs) have been shown to be safe and cost-effective in many specialties. Optimal treatment of 5th metatarsal base fractures remains controversial. Complications of base of 5th metatarsal fractures include delayed union and painful mal/non-union. Surgical fixation has been shown to enable faster return to sport, with lower faster union times and lower non-union rates than conservative management. The aims of this study were to assess whether the management of 5th metatarsal base fractures using a VFC model is safe, cost-effective and accceptable to the patients, whilst avoiding undesirable outcomes. Methods: All patients presenting to the VFC at our major trauma centre, with a 5th metatarsal base fracture between January 2019 and December 2019 were included in the study. One hundred and thirty six patients were identified. All patients had a standardised VFC treatment protocol including full weight bearing in a walker boot, rehabilitation planning to wean out of the boot and advice to contact the unit for follow-up if ongoing pain after 4 months. Minimum follow-up was one year. Patient records were retrospectively reviewed for baseline demographic data, including co-morbidities and smoking history. Overall complication rates, including mal and non-union as well as operative intervention rates were noted. Patients from the cohort who required face to face appointments were identified and the cause for return was identified. A cost analysis was also performed to evaluate the financial implications of the service. Results: Mean age was 41,6 years (18-92). Average time from ED attendance to VFC review was 2 days (1 - 5). Fractures were classified according to the Torg Classification with 106 (78%) Type 1 fractures, 15 (11%) Type 2 fractures and 15 (11%) Type 3 fractures. At VFC, 135/136 (99.2%) were discharged with the appropriate 5th metatarsal base fracture protocol. Twelve patients (8.8%) arranged further follow-up after initial discharge. The most common reason for return was ongoing pain (6/8 - 75.0%). This subgroup of the patients required an average of 3 (1-6) further appointments. There was 1 non-union during the study period. Based on 2 face to face visits on a traditional pathway, 248 clinic visits were saved with an approximate cost saving of nearly £40,000 ($55,500). Conclusion: Our study supports the management of 5th metatarsal base fractures in the VFC setting. We have shown that the VFC model, with well a defined protocol is both safe and cost effective. Fifth metatarsal base fractures have good outcomes with conservative management, removing the traditional need to have in-person clinic visits to confirm the diagnosis, management and prognosis.

Category: Midfoot/Forefoot; Trauma Introduction/Purpose: Lisfranc injuries represent a significant disruption to the complex articulations of the midfoot. Many of these injuries are unstable with displacement and articular incongruity. This necessitates surgical intervention with the primary goals of anatomic reduction and midfoot stability. Evidence around surgical treatments for Lisfranc complex injuries is limited by heterogeneity in outcome measures and small patient numbers. Dorsal bridge plating is a well-recognized surgical technique with the benefits of rigid stability and joint preservation. The primary aim of this study is to assess the midterm functional outcomes for patients treated with this technique at our major trauma centre. Additionally, we assess the complication profile and review for risk factors that influence the functional outcome. Methods: Eighty-five adult patients were identified as undergoing open reduction and dorsal bridge plate fixation for displaced, unstable Lisfranc injuries at our major trauma centre between January 2014 and January 2018. Supplemental Kirschner wire stabilization was used for the lateral column if necessitated by the injury pattern. Importantly, metalwork was not routinely removed. A retrospective review of case notes and imaging was conducted in order to collate demographic data including co- morbidities and smoking status. Patient-reported outcome measures were collected at final follow-up, with a minimum follow-up of 24 months. The Manchester-Oxford Foot Questionnaire summary index (MOXFQ-Index) was the primary patient-reported outcome. The American Orthopaedic Foot & Ankle Society (AOFAS) midfoot scale, complications, and all-cause re-operation rates were secondary outcome measures. Univariate and multivariate analyses were used to identify risk factors associated with poorer functional outcomes. Results: The mean follow-up in this study was 40.8 months (24 - 72). 61/85 patients (72%) had high-energy or crush mechanisms of injury. The mean MOXFQ-Index was 27.0 (SD 7.1). The mean AOFAS score was 72.6 (SD 11.6). 48/85 patients (56%) had injury patterns that included an intra-articular fracture and this was associated with poorer outcomes, with worse MOXFQ and AOFAS scores (both p

Background & Aims: Infection is a major problem in advanced liver disease secondary to monocyte dysfunction. Elevated prostaglandin (PG)E2 is a mediator of monocyte dysfunction in cirrhosis; thus, we examined PGE2 signalling in outpatients with ascites and in patients hospitalised with acute decompensation to identify potential therapeutic targets aimed at improving monocyte dysfunction. Methods: Using samples from 11 outpatients with ascites and 28 patients hospitalised with decompensated cirrhosis, we assayed plasma levels of PGE2 and lipopolysaccharide (LPS); performed quantitative real-time PCR on monocytes; and examined peripheral blood monocyte function. We performed western blotting and immunohistochemistry for PG biosynthetic machinery expression in liver tissue. Finally, we investigated the effect of PGE2 antagonists in whole blood using polychromatic flow cytometry and cytokine production. Results: We show that hepatic production of PGE2 via the cyclo-oxygenase 1–microsomal PGE synthase 1 pathway, and circulating monocytes contributes to increased plasma PGE2 in decompensated cirrhosis. Transjugular intrahepatic sampling did not reveal whether hepatic or monocytic production was larger. Blood monocyte numbers increased, whereas individual monocyte function decreased as patients progressed from outpatients with ascites to patients hospitalised with acute decompensation, as assessed by Human Leukocyte Antigen (HLA)–DR isotype expression and tumour necrosis factor alpha and IL6 production. PGE2 mediated this dysfunction via its EP4 receptor. Conclusions: PGE2 mediates monocyte dysfunction in decompensated cirrhosis via its EP4 receptor and dysfunction was worse in hospitalised patients compared with outpatients with ascites. Our study identifies a potential drug target and therapeutic opportunity in these outpatients with ascites to reverse this process to prevent infection and hospital admission. Lay summary: Patients with decompensated cirrhosis (jaundice, fluid build-up, confusion, and vomiting blood) have high infection rates that lead to high mortality rates. A white blood cell subset, monocytes, function poorly in these patients, which is a key factor underlying their sensitivity to infection. We show that monocyte dysfunction in decompensated cirrhosis is mediated by a lipid hormone in the blood, prostaglandin E2, which is present at elevated levels, via its EP4 pathway. This dysfunction worsens when patients are hospitalised with complications of cirrhosis compared with those in the outpatients setting, which supports the EP4 pathway as a potential therapeutic target for patients to prevent infection and hospitalisation.

Background: Skin conditions have multiple causes. Natural phages in the Ganga River have bactericidal qualities against a number of bacterial infections, which help resolve skin conditions. Materials and Methods: We collected water from upper reaches of the Ganga River where the number of isolates of phages was more than 200 according to a study of the National Environmental Engineering Institute, Nagpur. The water was collected in May 2020 before the onset of monsoons and stored with sediments so that the phages adsorbed in the sediments cleaned up the overlaying column of water of all coliforms. We supplied the water by post to a number of volunteers who took the water through oral, topical or nasal route as per their convenience. Thirty-nine of the 52 volunteers provided data by telephone on their skin conditions on which this study is based. Results: The results show that an improvement of 1.7 on Likert Scale of 1-10 is obtained on skin conditions as per assessment of the volunteers after a treatment of 100 days. Further improvement of 1.0 on Likert Scale was reported after 85 days of stoppage of treatment. Conclusions: Natural phages of Ganga river could provide an inexpensive treatment not only for skin conditions but other comorbidities as well because skin conditions have multiple causes and phages of Ganga water may work at multiple levels.

The present study aims to understand the high-temperature bending fatigue behavior at the stress-concentrated Y-shape junction of a component made of Tyranno SA3 fiber/BN interphase/SiC matrix composite. The SiC/SiC CMC component was processed via a hybrid technique by combining Chemical Vapor Infiltration (CVI) and Polymer Impregnation and Pyrolysis (PIP) processes. Two different types of tests, namely, point-load-bending-static-test and point-load-bending-fatigue-test, were performed at 1100 °C. The point-load-bending-static test revealed quasi-ductile or shear failure owing to the lower elastic modulus of the PIP-SiC matrix. The first matrix-cracking occurred when the high-stress region reached approximately 180 MPa, which was facilitated by the pores and cracks that remained after the PIP process around the intricate Y-shape junction of the sample. The point-load-bending-fatigue tests were performed under the maximum of the fatigue stresses ranging from 180 to 290 MPa. When the maximum of the fatigue stress was lower than 60% of the static strength, multiple matrix-cracking were pronounced such that the component did not fail and withstand 1000 fatigue cycles. At higher stresses of 250 and 290 MPa, delamination due to shear stress generation at the fiber tows interface and degradation of the BN interphase ultimately led to the fracture of the component at low fatigue cycles of less than 100. Moreover, the fracture morphology of the 290-MPa-fatigue sample showed brittle failure, which was due to matrix-crack-assisted oxygen embrittlement. In addition, a brief comparison between the point-load-bending-fatigue test and the conventional tension-compression fatigue test was discussed.

Abstract Background Recommended statistical methods for meta-analysis of diagnostic test accuracy studies require relatively complex bivariate statistical models which can be a barrier for non-statisticians. A further barrier exists in the software options available for fitting such models. Software accessible to non-statisticians, such as RevMan, does not support the fitting of bivariate models thus users must seek statistical support to use R, Stata or SAS. Recent advances in web technologies make analysis tool creation much simpler than previously. As well as accessibility, online tools can allow tailored interactivity not found in other packages allowing multiple perspectives of data to be displayed and information to be tailored to the user’s preference from a simple interface. We set out to: (i) Develop a freely available web-based “point and click” interactive tool which allows users to input their DTA study data and conduct meta-analyses for DTA reviews, including sensitivity analyses. (ii) Illustrate the features and benefits of the interactive application using an existing DTA meta-analysis for detecting dementia. Methods To create our online freely available interactive application we used the existing R packages lme4 and Shiny to analyse the data and create an interactive user interface respectively. Results MetaDTA, an interactive online application was created for conducting meta-analysis of DTA studies. The user interface was designed to be easy to navigate having different tabs for different functions. Features include the ability for users to enter their own data, customise plots, incorporate quality assessment results and quickly conduct sensitivity analyses. All plots produced can be exported as either .png or .pdf files to be included in report documents. All tables can be exported as .csv files. Conclusions MetaDTA, is a freely available interactive online application which meta-analyses DTA studies, plots the summary ROC curve, incorporates quality assessment results and allows for sensitivity analyses to be conducted in a timely manner. Due to the rich feature-set and user-friendliness of the software it should appeal to a wide audience including those without specialist statistical knowledge. We encourage others to create similar applications for specialist analysis methods to encourage broader uptake which in-turn could improve research quality.

BackgroundBehçet’s Disease (BD) is an autoimmune disease mostly presenting with recurrent oral and genital aphthosis, and uveitis. Patients are rarely refractory to immunosuppressive treatments. Autologous hematopoietic stem cell transplantation (aHSCT) is a standard of care in other autoimmune diseases. Some patients with BD have been treated with aHSCT based on compassionate use.ObjectivesEvaluate the outcome of aHSCT in adult patients with BD treated in member centers of the European Society for Blood and Marrow Transplantation (EBMT).MethodsAdults who received aHSCT primarily for BD were identified retrospectively in the EBMT registry and/or in published literature. Data were extracted from either medical records of the patient or from publications.ResultsEight out of 9 cases reported to the registry and extracted data of 2 further patients from literature were analyzed. Four were female, median age at onset of BD was 24y (range 9-50). Median age at aHSCT was 32y (27-51). Patients had received median 4 (2-11) previous lines of therapy (89% corticosteroids, 50% methotrexate, anti-TNFα therapy or cyclophosphamide). All patients had active disease before mobilization. Conditioning regimen was heterogeneous. Median follow-up was 48 months (range 6-240). No treatment-related mortality was reported. This procedure induced complete remission (CR) in 80%, partial remission in 10% and lack of response in 10% of the patients. Relapse rate was 30% (2 relapses in patients in CR and 1 relapse in the patient in PR) with panuveitis (n=1), aphthosis (n=2) and arthralgia (n=1). Six patients were in CR. No late complications were reported.ConclusionaHSCT has an acceptable safety profile and represents a feasible and relatively effective procedure in severe and conventional treatment-resistant cases of BD and has the potential to stabilize BD in patients with life-threatening involvements.

Conventional tracking approaches track objects using a rectangle bounding box. Gait, gesture and many medical analyses require non-rigid shape extraction. A non-rigid object tracking is more difficult because it needs more accurate object shape and background separation in contrast to rigid bounding boxes. Active contour plays a vital role in the retrieval of image shape. However, the large computation time involved in contour tracing makes its use challenging in video processing. This paper proposes a new formation of the region-based active contour model (ACM) using a mean-shift tracker for video object tracking and its shape retrieval. The removal of re-initialization and fast deformation of the contour is proposed to retrieve the shape of the desired object. A contour model is further modified using a mean-shift tracker to track and retrieve shape simultaneously. The experimental results and their comparative analysis concludes that the proposed contour-based tracking succeed to track and retrieve the shape of the object with 71.86% accuracy. The contour-based mean-shift tracker resolves the scale-orientation selection problem in non-rigid object tracking, and resolves the weakness of the erroneous localization of the object in the frame by the tracker.

Background A standardised approach to assessing COVID-19 survivors has not been established, largely due to the paucity of data on medium- and long-term sequelae. Interval chest radiography is recommended following community-acquired pneumonia; however, its utility in monitoring recovery from COVID-19 pneumonia remains unclear. Methods This was a prospective single-centre observational cohort study. Patients hospitalised with severe COVID-19 pneumonia (admission duration ≥48 h and oxygen requirement ≥40% or critical care admission) underwent face-to-face assessment at 4–6 weeks post-discharge. The primary outcome was radiological resolution of COVID-19 pneumonitis (Radiographic Assessment of Lung Oedema score

BackgroundRisk factors for the development of severe COVID-19 disease and death have been widely reported across several studies. Knowledge about the determinants of severe disease and mortality in the Indian context can guide early clinical management.MethodsWe conducted a hospital-based case control study across nine sites in India to identify the determinants of severe and critical COVID-19 disease.FindingsWe identified age above 60 years, duration before admission >5 days, chronic kidney disease, leucocytosis, prothrombin time > 14 sec, serum ferritin >250 ng/mL, d-dimer >0.5 ng/mL, pro-calcitonin >0.15 μg/L, fibrin degradation products >5 μg/mL, C-reactive protein >5 mg/L, lactate dehydrogenase >150 U/L, interleukin-6 >25 pg/mL, NLR ≥3, and deranged liver function, renal function and serum electrolytes as significant factors associated with severe COVID-19 disease.InterpretationWe have identified a set of parameters that can help in characterising severe COVID-19 cases in India. These parameters are part of routinely available investigations within Indian hospital settings, both public and private. Study findings have the potential to inform clinical management protocols and identify patients at high risk of severe outcomes at an early stage.