Miracle-dz/UniFAR-FTUs huggingface dataset:
Hidden dangers-prevalence of blood borne pathogens, hepatitis B, C, HIV and syphilis, among blood donors in Sierra Leone in 2016: opportunities for improvement: a retrospective, cross-sectional study

Introduction Transmissible blood-borne infections are a serious threat to blood transfusion safety in West African countries; and yet blood remains a key therapeutic product in the clinical management of patients. Sierra Leone screens blood donors for blood-borne infections but has not implemented prevention of mother-to-child transmission for hepatitis B. This study aimed to describe the overall prevalence of hepatitis B and C, HIV and syphilis among blood donors in Sierra Leone in 2016 and to compare the differences between volunteer versus family replacement donors, as well as urban versus rural donors. Methods Retrospective, cross-sectional study from January-December 2016 in five blood bank laboratories across the country. Routinely-collected programme data were analyzed; blood donors were tested with rapid diagnostic tests-HBsAg for HBV, anti-HCV antibody for HCV, antibodies HIV1&2 for HIV and TPHA for syphilis. Results There were 16807 blood samples analysed, with 80% from males; 2285 (13.6%) tested positive for at least one of the four pathogens. Overall prevalence was: 9.7% hepatitis B; 1.0% hepatitis C; 2.8% HIV; 0.8% syphilis. Prevalence was higher among samples from rural blood banks, the difference most marked for hepatitis C. The proportion of voluntary donors was 12%. Family replacement donors had a higher prevalence of hepatitis B, C and HIV than volunteers. Conclusion A high prevalence of blood-borne pathogens, particularly hepatitis B, was revealed in Sierra Leone blood donors. The study suggests the country should implement the prevention of mother-to-child transmission of hepatitis B and push to recruit more volunteer, non-remunerated blood donors.
Healing the heart of recovery

Background and Aim: Medicine is traditionally considered a healing profession, yet concepts of healing are rarely applied to mental illness, recovery being the dominant discourse. This article reports one aspect of the results of a broader exploration, through a service user lens, of aspects of place that facilitate healing in mental health care, with a resulting conceptualisation of healing. Method: The research material comprised the author’s historical writings of her experience of mental illness and recovery and in-depth individual interviews with 10 mental health service users. Analysed thematically, emerging ideas were further developed through an autoethnographically informed, reflexive and iterative process. Results: Healing is necessary when there has been a disruption of integrity and wholeness, experienced as suffering. Offering opportunities for connection, integration and transformation, and acquiring wisdom along the way, healing is a journey of exploration that takes time and is hard work. Discussion: Healing is conceptualised as the intensely personal experience at the heart of recovery, reminding us of the fundamental personal processes at the heart of our journeys. As a universal human experience, healing potentially removes the sense of othering that is at the heart of mental illness stigma.
Rab4A organizes endosomal domains for sorting cargo to lysosome-related organelles

ABSTRACT Sorting endosomes (SEs) are the regulatory hubs for sorting cargo to multiple organelles, including lysosome-related organelles, such as melanosomes in melanocytes. In parallel, melanosome biogenesis is initiated from SEs with the processing and sequential transport of melanocyte-specific proteins toward maturing melanosomes. However, the mechanism of cargo segregation on SEs is largely unknown. Here, RNAi screening in melanocytes revealed that knockdown of Rab4A results in defective melanosome maturation. Rab4A-depletion increases the number of vacuolar endosomes and disturbs the cargo sorting, which in turn lead to the mislocalization of melanosomal proteins to lysosomes, cell surface and exosomes. Rab4A localizes to the SEs and forms an endosomal complex with the adaptor AP-3, the effector rabenosyn-5 and the motor KIF3, which possibly coordinates cargo segregation on SEs. Consistent with this, inactivation of rabenosyn-5, KIF3A or KIF3B phenocopied the defects observed in Rab4A-knockdown melanocytes. Further, rabenosyn-5 was found to associate with rabaptin-5 or Rabip4/4′ (isoforms encoded by Rufy1) and differentially regulate cargo sorting from SEs. Thus, Rab4A acts a key regulator of cargo segregation on SEs. This article has an associated First Person interview with the first author of the paper. Summary: Rab4A controls cargo segregation by forming a complex with rabenosyn-5, KIF3 and AP-3 on sorting endosomes to divert the cargo toward melanosomes.
Prevalence and Characterization of Heterogeneous Variable-Number Tandem-Repeat Clusters Comprising Drug-Susceptible and/or Variable Resistant Mycobacterium tuberculosis Complex Isolates in the Netherlands from 2004 to 2016

The variable-number tandem-repeat (VNTR) typing method is used to study tuberculosis (TB) transmission. Clustering of Mycobacterium tuberculosis isolates with identical VNTR patterns is assumed to reflect recent transmission. ABSTRACT The variable-number tandem-repeat (VNTR) typing method is used to study tuberculosis (TB) transmission. Clustering of Mycobacterium tuberculosis isolates with identical VNTR patterns is assumed to reflect recent transmission. Hence, clusters are thought to be homogeneous regarding antibiotic resistance. In practice, however, heterogeneous clusters are also identified. This study investigates the prevalence and characteristics of heterogeneous VNTR clusters and assesses whether isolates in these clusters remain clustered when subjected to whole-genome sequencing (WGS). In the period from 2004 to 2016, 9,072 isolates were included. Demographic and epidemiological linkage data were obtained from the Netherlands Tuberculosis Register. VNTR clusters were defined as homogeneous when isolates shared identical resistance profiles or as heterogeneous if both susceptible and (variable) resistant isolates were found. Multivariate logistic regression analysis was performed to identify factors associated with heterogeneous clustering. Isolates from 2016 were subjected to WGS, and a genetic distance of 12 single nucleotide polymorphisms (SNPs) was used as the cutoff for WGS clustering. In total, 4,661/9,072 (51%) isolates were clustered into 985 different VNTR clusters, of which 217 (22%) were heterogeneous. Patient characteristics associated with heterogeneous clustering were non-Dutch ethnicity (odds ratio [OR], 1.46 [95% confidence interval {CI}, 1.22 to 1.75]), asylum seeker (OR, 1.51 [95% CI, 1.24 to 1.85]), extrapulmonary TB (OR, 1.26 [95% CI, 1.09 to 1.46]), previous TB diagnosis (OR, 1.38 [95% CI, 1.04 to 1.82]), and not being a contact of a TB patient (OR, 1.35 [95% CI, 1.08 to 1.69]). With WGS, 34% of heterogeneous and 78% of homogeneous isolates from 2016 remained clustered. Heterogeneous VNTR clusters are common but seem to be explained by a substantial degree of false clustering by VNTR typing compared to WGS.
Circulating Tumour DNA in Muscle-Invasive Bladder Cancer

Circulating tumour DNA (ctDNA) is an attractive tool in cancer research, offering many advantages over tissue samples obtained using traditional biopsy methods. There has been increasing interest in its application to muscle-invasive bladder cancer (MIBC), which is recognised to be a heterogeneous disease with overall poor prognosis. Using a range of platforms, studies have shown that ctDNA is detectable in MIBC and may be a useful biomarker in monitoring disease status and guiding treatment decisions in MIBC patients. Currently, with no such predictive or prognostic biomarkers in clinical practice to guide treatment strategy, there is a real unmet need for a personalised medicine approach in MIBC, and ctDNA offers an exciting avenue through which to pursue this goal. In this article, we present an overview of work to date on ctDNA in MIBC, and discuss the inherent challenges present as well as the potential future clinical applications.
Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study

Abstract Objectives To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk. Design Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach. Setting 25 cohorts from Europe, United States, east Asia, and Australia with genome wide genotyping and fracture data. Participants A discovery set of 37 857 fracture cases and 227 116 controls; with replication in up to 147 200 fracture cases and 150 085 controls. Fracture cases were defined as individuals (>18 years old) who had fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports. Instrumental variable analyses were performed to estimate effects of 15 selected clinical risk factors for fracture in a two-sample mendelian randomisation framework, using the largest previously published GWAS meta-analysis of each risk factor. Results Of 15 fracture associated loci identified, all were also associated with bone mineral density and mapped to genes clustering in pathways known to be critical to bone biology (eg, SOST, WNT16, and ESR1) or novel pathways (FAM210A, GRB10, and ETS2). Mendelian randomisation analyses showed a clear effect of bone mineral density on fracture risk. One standard deviation decrease in genetically determined bone mineral density of the femoral neck was associated with a 55% increase in fracture risk (odds ratio 1.55 (95% confidence interval 1.48 to 1.63; P=1.5×10−68). Hand grip strength was inversely associated with fracture risk, but this result was not significant after multiple testing correction. The remaining clinical risk factors (including vitamin D levels) showed no evidence for an effect on fracture. Conclusions This large scale GWAS meta-analysis for fracture identified 15 genetic determinants of fracture, all of which also influenced bone mineral density. Among the clinical risk factors for fracture assessed, only bone mineral density showed a major causal effect on fracture. Genetic predisposition to lower levels of vitamin D and estimated calcium intake from dairy sources were not associated with fracture risk.
Prevalence and Determinants of Stunting Among Preschool Children and Its Urban–Rural Disparities in Bangladesh

Background: Despite improvements in the reduction of child stunting rates over the last decade, poor nutritional status still remains a public health concern in Bangladesh, where young children are the most vulnerable. Objective: The objective of this study is to capture the prevalence and determinants of childhood stunting and document its urban–rural disparities in the context of Bangladesh. Methods: The study used data from the Bangladesh Demographic and Health Survey of 2014. A bivariate analysis was performed to find out the differentials in prevalence of stunting, and multivariate logistic regression was performed to also assess the association of stunting with potential risk factors. Results: The overall prevalence of stunting was 36.3% and was significantly higher in rural (38.1%) areas than urban (31.2%) areas. In all 3 regression models, significantly higher odds were found among children aged 36 to 47 months compared to 6 to 12 months and among the children from the poorest households. In rural areas, male children were significantly more likely to be stunted (odds ratio = 1.31; 95% confidence interval: 1.12-1.53). Other significant risk factors for childhood stunting were maternal education and body mass index, children suffering from diarrhea, initial breast-feeding, and administrative divisions. Conclusions: Disparities exist among urban and rural areas regarding stunting among the children younger than 5 in Bangladesh, which need to be reduced. Public health policies and interventions need to consider the risk factors in urban and rural areas separately.
Proinsulin in the identification and risk stratification of gestational diabetes mellitus: study protocol for a prospective, longitudinal cohort study

Introduction Gestational diabetes mellitus (GDM) is a common metabolic disorder occurring in up to 10% of pregnancies in the western world. Most women with GDM are asymptomatic; therefore, it is important to screen, diagnose and manage the condition as it is associated with an increased risk of maternal and perinatal complications. Diagnosis of GDM is made in the late second trimester or early third trimester because accurate diagnosis or risk stratification in the first trimester is still lacking. An increase in serum proinsulin may be seen earlier in pregnancy and before a change in glycaemic control can be identified. This study will aim to establish if fasting proinsulin concentrations at 16–18 weeks gestation will help to identify or risk stratify high-risk pregnant women with GDM. Methods and analysis This is a prospective, longitudinal cohort study. Two oral glucose tolerance tests will be carried out at 16–18 and 24–28 weeks gestation in 200 pregnant women with at least one risk factor for GDM (body mass index>30 kg/m2, previous macrosomic baby (>4.5 kg), previous gestational diabetes, first degree relative with type 2 diabetes mellitus) recruited from antenatal clinics. Blood samples will be taken fasting and at 30 min, 1 and 2 hours following the 75 g glucose load. In addition, a fasting blood sample will be taken 6-weeks post delivery. All samples will be analysed for glucose, insulin, C peptide and proinsulin. Recruitment began in November 2017. Optimal cut-off points for proinsulin to diagnose gestational diabetes according to National Institute for Health and Care Excellence (2015) criteria will be established by the receiver operating characteristic plot and sensitivity and specificity will be calculated to assess the diagnostic accuracy of proinsulin at 16–18 weeks gestation. Ethics and dissemination This study received ethical approval from the Wales Research Ethics Committee (Panel 6) (Ref. 17/WA/0194). Data will be presented at international conferences and published in peer-reviewed journals. Trial registration number ISRCTN16416602; Pre-results.
HDAC inhibition improves autophagic and lysosomal function to prevent loss of subcutaneous fat in a mouse model of Cockayne syndrome

The HDAC inhibitor SAHA rescues the skin phenotype in CSB-deficient mice by enhancing protein acetylation and inducing autophagy. Autophagy and adipose Hypersensitivity to sunlight and decreased subcutaneous fat are characteristics of Cockayne syndrome, a genetic disorder of premature aging. Majora and colleagues studied the role of autophagy underlying this skin phenotype using mice with a mutation in csb, a gene that causes Cockayne syndrome. They found an accumulation of autophagy-related proteins and lysosomal dysfunction in skin from csb mutant mice exposed to ultraviolet light. Treatment with a histone deacetylase inhibitor prevented loss of subcutaneous fat and rescued autophagic/lysosomal dysfunction. Further research is necessary to determine whether histone deacetylase inhibition can resolve other features of Cockayne syndrome, such as neurodegeneration. Cockayne syndrome (CS), a hereditary form of premature aging predominantly caused by mutations in the csb gene, affects multiple organs including skin where it manifests with hypersensitivity toward ultraviolet (UV) radiation and loss of subcutaneous fat. There is no curative treatment for CS, and its pathogenesis is only partially understood. Originally considered for its role in DNA repair, Cockayne syndrome group B (CSB) protein most likely serves additional functions. Using CSB-deficient human fibroblasts, Caenorhabditis elegans, and mice, we show that CSB promotes acetylation of α-tubulin and thereby regulates autophagy. At the organ level, chronic exposure of csbm/m mice to UVA radiation caused a severe skin phenotype with loss of subcutaneous fat, inflammation, and fibrosis. These changes in skin tissue were associated with an accumulation of autophagic/lysosomal proteins and reduced amounts of acetylated α-tubulin. At the cellular level, we found that CSB directly interacts with the histone deacetylase 6 (HDAC6) and the α-tubulin acetyltransferase MEC-17. Upon UVA irradiation, CSB is recruited to the centrosome where it colocalizes with dynein and HDAC6. Administration of the pan-HDAC inhibitor SAHA (suberoylanilide hydroxamic acid) enhanced α-tubulin acetylation, improved autophagic function in CSB-deficient models from all three species, and rescued the skin phenotype in csbm/m mice. HDAC inhibition may thus represent a therapeutic option for CS.
Lipschitz regularized Deep Neural Networks converge and generalize

Generalization of deep neural networks (DNNs) is an open problem which, if solved, could impact the reliability and verification of deep neural network architectures. In this paper, we show that if the usual fidelity term used in training DNNs is augmented by a Lipschitz regularization term, then the networks converge and generalize. The convergence is in the limit as the number of data points, $n\to \infty$, while also allowing the network to grow as needed to fit the data. Two regimes are identified: in the case of clean labels, we prove convergence to the label function which corresponds to zero loss, in the case of corrupted labels which we prove convergence to a regularized label function which is the solution of a limiting variational problem. In both cases, a convergence rate is also provided.
A framework for applying learning analytics in serious games for people with intellectual disabilities

Abstract: This paper proposes a systematic framework to integrate learning analytics into serious games for people with intellectual disabilities. Serious games for an inclusive learning environment need to be prudently designed with adaptive and measurable competencies to meet the needs of the target users. The recent emergence of learning analytics provides a capability to capture important data in real time from within the highly interactive nature of serious games to better understand and enhance the learning process. Although previous research has addressed different applications of learning analytics in serious games, few studies have investigated the needs of individuals with disabilities. This paper proposes a framework for serious games analytics specialised for people with intellectual disabilities (SGAPID) for the purpose of supporting the integration of learning analytics within serious games to create an inclusive learning environment. We provide a framework based on previous studies in both learning analytics, serious games and educational technologies for people with intellectual disabilities. The framework consists of three central components, namely learner profiling, learning adaptation and learning evaluation. It provides needed guidance for educational application developers and reflects the contemporary trends in educational technologies. The SGAPID framework will also be valuable for the design, implementation, evaluation and adaptation of serious games for inclusive learning and teaching at the group or individual level. [ABSTRACT FROM AUTHOR]
Vector OFDM Transmission Over Non-Gaussian Power Line Communication Channels

Most of the recent power line communication (PLC) systems and standards, both narrow-band and broadband, are based on orthogonal frequency-division multiplexing (OFDM). This multiplexing scheme, however, suffers from the high peak-to-average power ratio (PAPR), which can considerably impact the energy efficiency, size, and cost of PLC modems as well as cause electromagnetic compatibility (EMC) issues. This paper investigates the performance of vector OFDM (VOFDM), which has inherently better PAPR properties, over non-Gaussian broadband PLC channels equipped with two nonlinear preprocessors at the receiver. In addition, the low PAPR property of the VOFDM system is exploited to further enhance the efficiency of the nonlinear preprocessors. The achievable gains are studied in terms of the complementary cumulative distribution function of the PAPR, probability of noise detection error, and the signal-to-noise ratio at the output of the nonlinear preprocessors. For comparison's sake, the performance of conventional OFDM systems is also presented throughout this paper. Results reveal that the proposed system is able to provide up to 2-dB saving in the transmit power relative to the conventional OFDM under same system conditions, which eventually also translates into a system that is more resilient to EMC limits, reduced cost, and size of PLC modems. It is also shown that the achievable gains become more significant as the vector block size of the VOFDM system is increased.
Coordinated Tuning of Controller Parameters in AC/DC Grids for Power Oscillation Damping

Oscillatory modes in power systems will become more variable due to the increasing share of volatile renewable generation. Adding new or replacing existing controllers in power systems in order to damp such oscillations is an expensive and difficult task. Thus, new functions are required in order to optimally use existing controllers for the damping of variable oscillations. This paper presents a method for automatic parameter tuning of existing controllers in AC/DC power systems for optimal oscillation damping. For this purpose, we first present a detailed dynamic model of AC/DC grids with explicit dependencies on controller parameters. We then use H-infinity optimization to tune the controllers in the system. The efficiency of the proposed method is demonstrated with detailed rounded-mean-square simulations of a modified IEEE 39 bus power system.
Angular Resolution Estimation for Conformal Radar Antenna Arrays

The antenna is an important part of an automotive radar system and influences the sensor's performance, especially its angular behavior. Planar antennas have a limited view angle that can be enlarged by a conformal array. However, the evaluation of the system is more difficult because some assumptions are not valid anymore, e. g. the antenna elements are not identical. This paper attends the angular resolution in two ways. First, an incoherent superposition of transmit-receive patterns is used for all combinations of target angles. Second, an assumption allows the estimation with the ambiguity function by evaluating the width of the diagonal line. Therefore, a fast estimation of the expected angular resolution is possible.