Partial androgen insensitivity syndrome with Müllerian duct derivatives complicated by a testicular seminoma

Androgen insensitivity syndrome (AIS) is a condition that affects sexual development before birth and during puberty and is one of the more common disorders affecting masculinisation of the male genitalia. This rare syndrome (affecting 2–5 per 100,000 genetic males) is classified as complete (CAIS), partial (PAIS) or mild depending upon the extent of residual functional androgen receptors (AR) which in turn influence the phenotype. Mutations of AR have been reported in approximately 95% of persons with CAIS and in 10% with PAIS.1 Genital ambiguity is variable in PAIS with a frequent phenotype of micropenis, posterior hypospadias and cryptorchidism. PAIS has a higher risk of associated malignancy than in CAIS.2 Current evidence recommends the retention of cryptorchid testes through puberty for hormone production benefits, including bone and secondary sexual development.3 Müllerian duct derivatives (such as fallopian tubes, uterus, cervix and upper vagina) are usually absent in patients with AIS but the occasional presence in some raise the possibility of either defective production or response to Müllerian inhibitory factor (MIF)

Study protocol: The Dutch 20|30 Postmeningitis study: a cross-sectional follow-up of two historical childhood bacterial meningitis cohorts on long-term outcomes

BACKGROUND: Bacterial meningitis (BM) is a serious, life-threatening infectious disease of the central nervous system that often occurs in young children. The most common severe to moderate sequelae following BM are sensorineural hearing loss, neuromotor disabilities and mental retardation, while subtle sequelae include academic and behavioral disabilities. It is largely unknown whether these more subtle sequelae persist into adolescence and adulthood. Therefore, this study will investigate the very long-term effects of childhood BM in later life. Better understanding of long-term effects and early identification of adverse outcomes after BM are essential for more timely interventions. Additionally, certain single nucleotide polymorphisms (SNPs) are associated with disease severity and might predict adverse sequelae. These include SNPs in genes encoding for pathogen recognition and immune response upon infection. Accordingly, a secondary objective of this study is to investigate the role of genetic variation in BM and use any insights to predict short- and long-term outcomes. METHODS: In the Dutch 20|30 Postmeningitis study, adolescents and young adults (n = 947) from two historical cohorts with a prior episode of BM during childhood will be enrolled into a cross-sectional follow-up investigation using mainly questionnaires that examine executive and behavioral functioning, health-related quality of life, subjective hearing, mood and sleeping disorders, academic performance, and economic self-sufficiency. The results will be compared to normative data by one-sample t-tests. Multivariable regression analysis will be used to assess for any associations with causative pathogens and severity of BM. Participants that complete the questionnaires will be approached to provide a swab for buccal DNA and subsequent sequencing analyses. Logistic regression models will be used to predict sequelae. DISCUSSION: The unique follow-up duration of this cohort will enable us to gain insights into the possible very long-term adverse effects of childhood BM and how these might impact on quality of life. The investigation of host genetic factors will contribute to the development of prediction models which will serve as prognostic tools to identify children who are at high risk of adverse outcome after BM. TRIAL REGISTRATION: Dutch Trial Register NTR-6891. Retrospectively registered 28 December 2017

Elastic net penalized Quantile Regression Model and Empirical Mode Decomposition for Improving the Accuracy of the Model Selection

In quantile regression models, numerous penalization methods have been developed to deal with ordinary least-squares method problems. Such methods are ridge penalized quantile regression, lasso penalized quantile regression, and elastic net penalized quantile regression which are used for variable selection and regularization and deals with the multicollinearity problem when it exists between the predictor variables. However, the variables of interest are often represented through time series processes, in which such time series data are often non-stationary and non-linear, which leads to poor accuracy of the resultant regression models and hence results with less reliability. The EMD-EnetQR method is proposed to address this issue, which consists of applying the empirical mode decomposition (EMD) algorithm to time series data and then using the resulting components in penalized quantile regression models. This study aims to apply the proposed EMD-QREnet method to determine the influence of the decomposition components of the original time series predictor variables on the response variable to build a model fit and improve prediction accuracy. Furthermore, this study addressed the multicollinearity between the decomposition components. Simulation studies and real dataset applications were conducted. The results show that the proposed EMDQREnet method, in most cases, outperforms the other methods by improving prediction accuracy

Prevalence of hepatitis B and C and assessment of responsible risk factors among the vulnerable β-thalassemic patients of Azad Kashmir, Pakistan

Approximately 350 million patients of hepatitis B and 170 million patients of Hepatitis C are present worldwide according to WHO. Many risk factors are involved in the transmission of theses deadly viral infections but blood transfusion in Beta thalassemic patients is working with two faces, one as remedy and the other is key risk factor in the spread of silent killers. Thalassemia patients registered in Combine Military Hospital (CMH) Rawalakot and Sheikh Khalifa Bin Zayed Al-Nahyan Hospital, Muzaffarabad Azad Jammu and Kashmir Pakistan were studied for the viral hepatitis B and C prevalence. A total of 303 (including 164 males and 139 females) individuals, aged between 1 and 12 years were studied. All the understudy participants were interviewed through questionnaire method. After taking written consent from each participant or guardian, 5 ml of blood was collected from each participant and brought to the working laboratory for HBV and HCV screening through ICT kit method. All ICT positive samples were further confirmed through ELISA. Individuals 25(8.2%) were found positive for both hepatitis B surface Antigen (HBsAg) and Anti hepatitis C antibody (Anti-HCV antibody) after initial screening with no coinfection of both diseases. Out of 25 total infected individuals, 05(1.6%) were found HBsAg positive and 20(6.6%) were found anti-HCV positive. All the ICT positive individuals were further confirmed by quantitative Enzyme Linked Immunosorbent Assay (ELISA) and 23(7.6%) individuals were confirmed for both hepatitis B and C including 05(1.6%) HBsAg positive as well as 18(5.9%) anti-HCV antibody positive individuals. We can conclude that 8.2% prevalence of hepatitis B and C among thalassemic patients is an alarming health concern which directly indicates to pay attention for ensuring 100% safe blood transfusion

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Search for the lepton-flavour violating decay D0→e±μ∓D^0 \to e^\pm\mu^\mp

A search for the lepton-flavour violating decay $D^0 \to e^\pm \mu^\mp$ is made with a dataset corresponding to an integrated luminosity of $3.0$ fb$^{-1}$ of proton-proton collisions at centre-of-mass energies of $7$ TeV and $8$ TeV, collected by the LHCb experiment. Candidate $D^0$ mesons are selected using the decay $D^{*+} \to D^0 \pi^+$ and the $D^0 \to e^\pm \mu^\mp$ branching fraction is measured using the decay mode $D^0 \to K^- \pi^+$ as a normalisation channel. No significant excess of $D^0 \to e^\pm \mu^\mp$ candidates over the expected background is seen, and a limit is set on the branching fraction, $\mathcal{B}(D^0 \to e^\pm \mu^\mp) < 1.3 \times 10^{-8}$, at 90 % confidence level. This is an order of magnitude lower than the previous limit and it further constrains the parameter space in some leptoquark models and in supersymmetric models with R-parity violation.A search for the lepton-flavour violating decay D0→e±μ∓ is made with a dataset corresponding to an integrated luminosity of 3.0fb−1 of proton–proton collisions at centre-of-mass energies of 7 TeV and 8 TeV , collected by the LHCb experiment. Candidate D0 mesons are selected using the decay D⁎+→D0π+ and the D0→e±μ∓ branching fraction is measured using the decay mode D0→K−π+ as a normalization channel. No significant excess of D0→e±μ∓ candidates over the expected background is seen, and a limit is set on the branching fraction, B(D0→e±μ∓)<1.3×10−8 , at 90% confidence level. This is an order of magnitude lower than the previous limit and it further constrains the parameter space in some leptoquark models and in supersymmetric models with R-parity violation.A search for the lepton-flavour violating decay $D^0 \to e^\pm \mu^\mp$ is made with a dataset corresponding to an integrated luminosity of 3.0 fb$^{-1}$ of proton-proton collisions at centre-of-mass energies of $7$ TeV and $8$ TeV, collected by the LHCb experiment. Candidate $D^0$ mesons are selected using the decay $D^{*+} \to D^0 \pi^+$ and the $D^0 \to e^\pm \mu^\mp$ branching fraction is measured using the decay mode $D^0 \to K^-\pi^+$ as a normalisation channel. No significant excess of $D^0 \to e^\pm \mu^\mp$ candidates over the expected background is seen, and a limit is set on the branching fraction, $\mathcal{B}(D^0 \to e^\pm \mu^\mp) < 1.3 \times 10^{-8}$, at 90 % confidence level. This is an order of magnitude lower than the previous limit and it further constrains the parameter space in some leptoquark models and in supersymmetric models with R-parity violation

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2•72 (95% uncertainty interval [UI] 2•66–2•79) in 2000 to 2•31 (2•17–2•46) in 2019. Global annual livebirths increased from 134•5 million (131•5–137•8) in 2000 to a peak of 139•6 million (133•0–146•9) in 2016. Global livebirths then declined to 135•3 million (127•2–144•1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2•1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27•1% (95% UI 26•4–27•8) of global livebirths. Global life expectancy at birth increased from 67•2 years (95% UI 66•8–67•6) in 2000 to 73•5 years (72•8–74•3) in 2019. The total number of deaths increased from 50•7 million (49•5–51•9) in 2000 to 56•5 million (53•7–59•2) in 2019. Under-5 deaths declined from 9•6 million (9•1–10•3) in 2000 to 5•0 million (4•3–6•0) in 2019. Global population increased by 25•7%, from 6•2 billion (6•0–6•3) in 2000 to 7•7 billion (7•5–8•0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58•6 years (56•1–60•8) in 2000 to 63•5 years (60•8–66•1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation: Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global burden of 87 risk factors in 204 countries and territories, 1990�2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods: GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk�outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk�outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk�outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10·8 million (95 uncertainty interval UI 9·51�12·1) deaths (19·2% 16·9�21·3 of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8·71 million (8·12�9·31) deaths (15·4% 14·6�16·2 of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253�350) DALYs (11·6% 10·3�13·1 of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0�9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10�24 years, alcohol use for those aged 25�49 years, and high systolic blood pressure for those aged 50�74 years and 75 years and older. Interpretation: Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Conservative management versus volar plating for dorsally displaced distal radius fractures in the elderly: A randomized control trial.

This randomized trial aims to compare the clinical, and radiological outcomes between plaster cast and volar plating for distal radius fractures (DRF) in the elderly at six months, and one-year. A randomized trial was performed at Jinnah Postgraduate Medical Centre between February 2015 and April 2020. The study included patients that were above 60 years but under 75 with an isolated, closed, unilateral, dorsally displaced DRF. Randomization into two groups (casting or plating) was based on a computer-generated algorithm stratified by age group and AO/OTA fracture type. The primary outcome was Patient Rated Wrist Evaluation score. Secondary clinical outcomes were active range of motion, grip strength, the Mayo's wrist score and the quick Disability Arm, Shoulder, Hands scale. Patient's satisfaction was evaluated with use of a SF-12 questionnaire and finally complications were recorded. This trial has shown that there is no significant difference in clinical outcomes of DRF at six and twelve months follow up when treated by cast immobilization or plating. Although, the radiological parameters and the number of complications were significantly higher in the immobilization group. The results of the trial have shown that plating and casting are equally effective in achieving satisfactory patient reported and clinical outcomes at intermediate and final follow-up restoring patient satisfaction.Trial registration: The trial is registered in the Chinese Clinical Trial Registry. The trial registration number is ChiCTR2000032843, and the URL is: http://www.chictr.org.cn/searchprojen.aspx

Crystal structure of a dithiocarbazate diester: E-bis(3-methylbenzyl)-1-(6-methylpyridin-2-yl)ethylidene-carbohydrazonod ithioate, C25H27N3S2

C25H27N3S2, monoclinic, P2(1)/n (no. 14), a = 8.2943(4) angstrom, b = 8.5039(4) angstrom, c = 33.587(2) angstrom, beta = 95.921(4)degrees, V = 2356.4 angstrom(3), Z = 4, R-gt(F) = 0.0451, wR(ref)(F-2) = 0.1340, T = 150 K