BCL11A intellectual developmental disorder: defining the clinical spectrum and genotype-phenotype correlations.

An increasing number of individuals with intellectual developmental disorder (IDD) and heterozygous variants in BCL11A are identified, yet our knowledge of manifestations and mutational spectrum is lacking. To address this, we performed detailed analysis of 42 individuals with BCL11A-related IDD (BCL11A-IDD, a.k.a. Dias-Logan syndrome) ascertained through an international collaborative network, and reviewed 35 additional previously reported patients. Analysis of 77 affected individuals identified 60 unique disease-causing variants (30 frameshift, 7 missense, 6 splice-site, 17 stop-gain) and 8 unique BCL11A microdeletions. We define the most prevalent features of BCL11A-IDD: IDD, postnatal-onset microcephaly, hypotonia, behavioral abnormalities, autism spectrum disorder, and persistence of fetal hemoglobin (HbF), and identify autonomic dysregulation as new feature. BCL11A-IDD is distinguished from 2p16 microdeletion syndrome, which has a higher incidence of congenital anomalies. Our results underscore BCL11A as an important transcription factor in human hindbrain development, identifying a previously underrecognized phenotype of a small brainstem with a reduced pons/medulla ratio. Genotype-phenotype correlation revealed an isoform-dependent trend in severity of truncating variants: those affecting all isoforms are associated with higher frequency of hypotonia, and those affecting the long (BCL11A-L) and extra-long (-XL) isoforms, sparing the short (-S), are associated with higher frequency of postnatal microcephaly. With the largest international cohort to date, this study highlights persistence of fetal hemoglobin as a consistent biomarker and hindbrain abnormalities as a common feature. It contributes significantly to our understanding of BCL11A-IDD through an extensive unbiased multi-center assessment, providing valuable insights for diagnosis, management and counselling, and into BCL11As role in brain development

Global, regional, and national levels of maternal mortality, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Background In transitioning from the Millennium Development Goal to the Sustainable Development Goal era, it is imperative to comprehensively assess progress toward reducing maternal mortality to identify areas of success, remaining challenges, and frame policy discussions. We aimed to quantify maternal mortality throughout the world by underlying cause and age from 1990 to 2015. Methods We estimated maternal mortality at the global, regional, and national levels from 1990 to 2015 for ages 10–54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories, 11 of which were analysed at the subnational level. We quantified eight underlying causes of maternal death and four timing categories, improving estimation methods since GBD 2013 for adult all-cause mortality, HIV-related maternal mortality, and late maternal death. Secondary analyses then allowed systematic examination of drivers of trends, including the relation between maternal mortality and coverage of specific reproductive health-care services as well as assessment of observed versus expected maternal mortality as a function of Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Findings Only ten countries achieved MDG 5, but 122 of 195 countries have already met SDG 3.1. Geographical disparities widened between 1990 and 2015 and, in 2015, 24 countries still had a maternal mortality ratio greater than 400. The proportion of all maternal deaths occurring in the bottom two SDI quintiles, where haemorrhage is the dominant cause of maternal death, increased from roughly 68% in 1990 to more than 80% in 2015. The middle SDI quintile improved the most from 1990 to 2015, but also has the most complicated causal profile. Maternal mortality in the highest SDI quintile is mostly due to other direct maternal disorders, indirect maternal disorders, and abortion, ectopic pregnancy, and/or miscarriage. Historical patterns suggest achievement of SDG 3.1 will require 91% coverage of one antenatal care visit, 78% of four antenatal care visits, 81% of in-facility delivery, and 87% of skilled birth attendance. Interpretation Several challenges to improving reproductive health lie ahead in the SDG era. Countries should establish or renew systems for collection and timely dissemination of health data; expand coverage and improve quality of family planning services, including access to contraception and safe abortion to address high adolescent fertility; invest in improving health system capacity, including coverage of routine reproductive health care and of more advanced obstetric care—including EmOC; adapt health systems and data collection systems to monitor and reverse the increase in indirect, other direct, and late maternal deaths, especially in high SDI locations; and examine their own performance with respect to their SDI level, using that information to formulate strategies to improve performance and ensure optimum reproductive health of their population. Funding Bill & Melinda Gates Foundation

Criminalizing Rape Within Marriage

The paper is an attempt to bring marital rape under the purview of legal discourse in India with substantive equality approach to problematize the existing defined structure of Indian Rape Law. This paper takes up the challenge to create a legal language on the issue of rape within marriage which is till now absent from the legal and social scenario. The equal treatment of women before and under the law within the context of marital rape is critical to ensuring the recognition of women as full citizens, and ensuring their freedom from violence. This paper examines the following questions: how marital rape contributes to and results from women‘s inequality; how the discriminatory roots of the historical- cultural rationales contributes to the exemption of marital rape from the Indian legal system; how the issue of marital rape has been debated in personal-political scenario from the feminist viewpoint; how equality jurisprudence can support the case for the legal treatment of marital rape claims. This paper questions the socio-legal passivity about the suppression of married women; cultivate the knowledge that helps women to generate their own thinking and to apply that in creating the new subjects, to make the women able to express their disagreements about the consent and to make them aware of their active sexuality to provide them bodily integrity. The paper is, thus, an attempt to emphasise the need to transform the prevailing masochistic heterosexual socio- legal matrix. The paper underlines the need to bring the issue of marital rape in the political sphere by bringing this to the purview of Indian law in both formal and substantive manner.</jats:p

A Review on Intrusion Detection System Based on Various Learning Techniques

In this world of the Internet, security plays an important role as Internet users grow rapidly. Security in the network is one of the modern periods' main issues. In the last decade, the exponential growth and massive use of the Internet have enabled system security vulnerabilities a critical aspect. Intrusion detection system to track unauthorized access as well as exceptional attacks through secured networks. Several experiments on the IDS have been carried out in recent years. And to know the current state of machine learning approaches to address the issue of intrusion detection. IDS is commonly used for the detection and recognition of cyberattacks at the network and host stage, in a timely and automatic manner. This research assesses the creation of a deep neural network (DNN), a form of deep learning model as well as ELM to detect unpredictable and unpredictable cyber-attacks.</jats:p

A Review on Intrusion Detection System Based on Various Learning Techniques

In this world of the Internet, security plays an important role as Internet users grow rapidly. Security in the network is one of the modern periods’ main issues. In the last decade, the exponential growth and massive use of the Internet have enabled system security vulnerabilities a critical aspect. Intrusion detection system to track unauthorized access as well as exceptional attacks through secured networks. Several experiments on the IDS have been carried out in recent years. And to know the current state of machine learning approaches to address the issue of intrusion detection. IDS is commonly used for the detection and recognition of cyberattacks at the network and host stage, in a timely and automatic manner. This research assesses the creation of a deep neural network (DNN), a form of deep learning model as well as ELM to detect unpredictable and unpredictable cyber-attacks.</jats:p