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    Performance of immune-based and microbiological tests in children with TB meningitis in Europe - a multi-center Paediatric Tuberculosis Network European Trials Group (ptbnet) study.

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    INTRODUCTION Tuberculous meningitis (TBM) is often diagnostically challenging. Only limited data exist on the performance of interferon-gamma release assays (IGRA) and molecular assays in children with TBM in routine clinical practice, particularly in the European setting. METHODS Multicenter, retrospective study involving 27 healthcare institutions providing care for children with tuberculosis (TB) in nine European countries. RESULTS Of 118 children included, 54 (45.8%) had definite, 38 (32.2%) probable and 26 (22.0%) possible TBM; 39 (33.1%) had TBM grade 1, 68 (57.6%) grade 2 and 11 (9.3%) grade 3. Of 108 patients who underwent cranial imaging 90 (83.3%) had ≥1 abnormal finding consistent with TBM. At the 5 mm cut-off the tuberculin skin test had a sensitivity of 61.9% (95%CI: 51.2-71.6%); at the 10 mm cut-off 50.0% (95%CI: 40.0-60.0%). The test sensitivities of QuantiFERON-TB and T-SPOT.TB assays were 71.7% (95%CI: 58.4-82.1%) and 82.5% (95%CI: 58.2-94.6%), respectively (p=0.53). Indeterminate results were common, occurring in 17.0% of QuantiFERON-TB assays performed. Cerebrospinal fluid (CSF) cultures were positive in 50.0% (95%CI: 40.1-59.9%), and CSF polymerase-chain-reaction (PCR) in 34.8% (95%CI: 22.9-43.7%). In the subgroup of children who had TST, IGRA, CSF culture and CSF PCR performed simultaneously, 84.4% had at least one positive test result (95%CI: 67.8%-93.6%). CONCLUSIONS Existing immunological and microbiological TB tests have suboptimal sensitivity in children with TBM, with each test producing false-negative results in a substantial proportion of patients. Combining immune-based tests with CSF culture and CSF PCR results in considerably higher positive diagnostic yields, and should therefore be standard clinical practice in high-resource settings

    The importance of language in engagement between health-care professionals and people living with obesity: a joint consensus statement.

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    Obesity is a chronic condition that requires long-term management and is associated with unprecedented stigma in different settings, including during interactions with the health-care system. This stigma has a negative effect on the mental and physical health of people with obesity and can lead to avoidance of health care and disruption of the doctor-patient relationship. Considerable evidence exists to suggest that simply having a conversation about obesity can lead to weight loss, which translates into health benefits. However, both health-care practitioners and people living with obesity report apprehension in initiating this conversation. We have collaborated with stakeholders from Obesity UK, physicians, dieticians, clinical psychologists, obesity researchers, conversation analysts, nurses, and representatives from National Health Service England Diabetes and Obesity. This group has contributed to the production of this consensus statement, which addresses how people living with obesity wish to have their condition referred to and provides practical guidance for health-care professionals to facilitate collaborative and supportive discussions about obesity. Expert stakeholders consider that changes to language used at the point of care can alleviate the stigma of obesity within the health-care system and support improved outcomes for both people living with obesity and for the health-care system

    The ballistic performance of bone when impacted by fragments.

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    Physical models are required to generate the underlying algorithms that populate computer simulations of the effects of explosive fragmenting devices. These models and simulations are used for understanding weapon performance, designing buildings and optimising personal protective equipment. Previous experimental work has investigated the performance of skin and muscle when subjected to fragmentation threats, but limited evidence exists for the performance of bone when impacted by fragments. In the current work, ballistic testing was conducted using two types of internationally recognised steel fragment simulating projectiles (FSPs): (i) 5.5 mm diameter (0.68 g) ball bearing (BBs) and (ii) 1.10 g chisel nosed (CN). These projectiles were fired at isolated swine ribs at impact velocities between 99 and 1265 m/s. Impact events were recorded using a high-speed camera. Selected specimens were analysed post-impact with plain x-radiographs and micro-CT scanning to determine damage to the bone architecture. Bones were perforated with a kinetic energy density (KED) as low as 0.14 J/mm. Energy transfer to the bone was greater for the CN FSPs, resulting in increased bone damage and the production of secondary bone fragments. The manner in which the bones failed with faster velocity impacts (> 551 m/s; KED > 6.44 J/mm) was analogous to the behaviour of a brittle material. Slower velocity impacts (< 323 m/s; KED < 1.49 J/mm) showed a transition in failure mode with the bone displaying the properties of an elastic, plastic and brittle material at various points during the impact. The study gives critical insight into how bone behaves under these circumstances

    Thrombocytopenia as an initial manifestation of Covid-19; Case Series and Literature review.

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    Covid-19 has emerged as a global threat that has claimed millions of lives until now. Haematological manifestation as an initial presentation of this deadly virus is not frequently reported in the literature. We hereby report a case series of asymptomatic patients with severe thrombocytopenia which was later found to be Covid induced

    Management challenges for chronic dysimmune neuropathies during the COVID-19 pandemic.

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    Since March 2020, the COVID-19 pandemic has led to the need to re-think the delivery of services to patients with chronic dysimmune neuropathies. Telephone/video consultations have become widespread but have compounded concerns about objective evaluation. Therapeutic decisions need, more than ever before, to be considered in the best interests of both patients, and society, while not denying function-preserving/restoring treatment. Immunoglobulin therapy and plasma exchange, for those treated outside of the home, expose patients to the hazards of hospital or outpatient infusion centers. Steroid therapy initiation and continuation pose increased infectious risk. Immunosuppressant therapy similarly becomes highly problematic, with the risks of treatment continuation enhanced by uncertainties regarding duration of the pandemic. The required processes necessitate considerable time and effort especially as resources and staff are re-deployed to face the pandemic, but are essential for protecting this group of patients and as an integral part of wider public health actions

    Is water-soluble contrast enema examination for integrity of rectal anastomosis necessary prior to ileostomy reversal?

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    Background and Aim Routine use of water-soluble contrast enema (WSCE) to assess anastomotic integrity is debated. This study aimed to evaluate the role of WSCE to assess anastomotic integrity following anterior resections (AR) with defunctioning stoma prior to reversal and identify factors to limit its selective use. Methods This retrospective study evaluated all WSCE performed over a 7-year period at a high-volume colorectal unit. Risk factors for radiological abnormality/leak, including malignancy, chemoradiotherapy, and immediate postoperative complications, were recorded. A gastrointestinal specialist radiologist and surgeon validated all WSCEs reported as abnormal. Results Of the 486 WSCE studies identified, 92 were excluded (repeat studies ( = 51), pediatric cases [ = 2], no AR [ = 39]). A total of 394 WSCE studies were evaluated (260 cancer; 134 noncancer patients); 14% (37/260) of cancer patients and 8% (10/134) of noncancer patients had abnormal studies ( = 0.072). Of the 37 abnormal studies in cancer patients, 73% (27/37) radiological leaks were found, and 41% ( = 11/27) of these patients had postoperative complications. Of the 10 abnormal studies in noncancer patients, 20% (2/10) radiological leaks were found, but none of these patients had postoperative complications. Overall leak rates were 7% (29/394), and rates were significantly higher in cancer patients than noncancer patients (10 2%, = 0.005). Conclusion Routine use of WSCE may not be necessary prior to reversal. WSCE should be selectively used in event of postoperative leak or complications. Noncancer resections are less likely demonstrate a leak

    Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study.

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    BACKGROUND Brentuximab vedotin was approved for adult patients with CD30-expressing cutaneous T-cell lymphoma treated with prior systemic therapy based on improved response rates and progression-free survival with brentuximab vedotin (1.8 mg/kg once every 3 weeks; ≤16 cycles) versus physician's choice (methotrexate/bexarotene; ≤48 weeks) in the phase III ALCANZA study. Quality of life (QoL) in ALCANZA patients was also examined. METHODS QoL measures in ALCANZA were based on the Skindex-29, Functional Assessment of Cancer Therapy-General (FACT-G) and European QoL 5-dimension (EQ-5D) questionnaires. RESULTS Mean maximum reduction from the baseline Skindex-29 symptom domain score (key secondary end-point) was greater with brentuximab vedotin than physician's choice (-27.96 versus -8.62); the difference, -18.9 (95% confidence interval -26.6, -11.2; adjusted p < 0.001), exceeded the study-defined minimally important difference (9.0-12.3). Mean changes from baseline to end-of-treatment visit total FACT-G scores were similar with brentuximab vedotin and physician's choice (0.15 versus -2.29). EQ-5D changes were also comparable between arms. Among brentuximab vedotin-treated patients with peripheral neuropathy (PN), mean maximum reduction in Skindex-29 symptom domain was -35.54 versus -11.11 in patients without PN. PN had no meaningful effect on FACT-G and EQ-5D QoL scores. CONCLUSIONS In summary, brentuximab vedotin produced superior reductions in symptom burden compared with physician's choice, without adversely impacting QoL. QoL was unaffected by the presence of PN in brentuximab vedotin-treated patients. CLINICAL TRIAL REGISTRATION NCT01578499

    Machine learning for high-throughput field phenotyping and image processing provides insight into the association of above and below-ground traits in cassava ( Crantz).

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    Background Rapid non-destructive measurements to predict cassava root yield over the full growing season through large numbers of germplasm and multiple environments is a huge challenge in Cassava breeding programs. As opposed to waiting until the harvest season, multispectral imagery using unmanned aerial vehicles (UAV) are capable of measuring the canopy metrics and vegetation indices (VIs) traits at different time points of the growth cycle. This resourceful time series aerial image processing with appropriate analytical framework is very important for the automatic extraction of phenotypic features from the image data. Many studies have demonstrated the usefulness of advanced remote sensing technologies coupled with machine learning (ML) approaches for accurate prediction of valuable crop traits. Until now, Cassava has received little to no attention in aerial image-based phenotyping and ML model testing. Results To accelerate image processing, an automated image-analysis framework called CIAT Pheno-i was developed to extract plot level vegetation indices/canopy metrics. Multiple linear regression models were constructed at different key growth stages of cassava, using ground-truth data and vegetation indices obtained from a multispectral sensor. Henceforth, the spectral indices/features were combined to develop models and predict cassava root yield using different Machine learning techniques. Our results showed that (1) Developed CIAT pheno-i image analysis framework was found to be easier and more rapid than manual methods. (2) The correlation analysis of four phenological stages of cassava revealed that elongation (EL) and late bulking (LBK) were the most useful stages to estimate above-ground biomass (AGB), below-ground biomass (BGB) and canopy height (CH). (3) The multi-temporal analysis revealed that cumulative image feature information of EL + early bulky (EBK) stages showed a higher significant correlation ( = 0.77) for Green Normalized Difference Vegetation indices (GNDVI) with BGB than individual time points. Canopy height measured on the ground correlated well with UAV (CHuav)-based measurements ( = 0.92) at late bulking (LBK) stage. Among different image features, normalized difference red edge index (NDRE) data were found to be consistently highly correlated ( = 0.65 to 0.84) with AGB at LBK stage. (4) Among the four ML algorithms used in this study, k-Nearest Neighbours (kNN), Random Forest (RF) and Support Vector Machine (SVM) showed the best performance for root yield prediction with the highest accuracy of R = 0.67, 0.66 and 0.64, respectively. Conclusion UAV platforms, time series image acquisition, automated image analytical framework (CIAT Pheno-i), and key vegetation indices (VIs) to estimate phenotyping traits and root yield described in this work have great potential for use as a selection tool in the modern cassava breeding programs around the world to accelerate germplasm and varietal selection. The image analysis software (CIAT Pheno-i) developed from this study can be widely applicable to any other crop to extract phenotypic information rapidly

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