The number of privately treated tuberculosis cases in India: an estimation from drug sales data

Background Understanding the amount of tuberculosis managed by the private sector in India is crucial to understanding the true burden of the disease in the country, and thus globally. In the absence of quality surveillance data on privately treated patients, commercial drug sales data offer an empirical foundation for disease burden estimation. Methods We used a large, nationally representative commercial dataset on sales of 189 anti-tuberculosis products available in India to calculate the amount of anti-tuberculosis treatment in the private sector in 2013–14. We corrected estimates using validation studies that audited prescriptions against tuberculosis diagnosis, and estimated uncertainty using Monte Carlo simulation. To address implications for numbers of patients with tuberculosis, we explored varying assumptions for average duration of tuberculosis treatment and accuracy of private diagnosis. Findings There were 17·793 million patient-months (95% credible interval 16·709 million to 19·841 million) of anti-tuberculosis treatment in the private sector in 2014, twice as many as the public sector. If 40–60% of private-sector tuberculosis diagnoses are correct, and if private-sector tuberculosis treatment lasts on average 2–6 months, this implies that 1·19–5·34 million tuberculosis cases were treated in the private sector in 2014 alone. The midpoint of these ranges yields an estimate of 2·2 million cases, two to three times higher than currently assumed. Interpretation India's private sector is treating an enormous number of patients for tuberculosis, appreciably higher than has been previously recognised. Accordingly, there is a re-doubled need to address this burden and to strengthen surveillance. Tuberculosis burden estimates in India and worldwide require revision

An algorithm for heart rate extraction from acoustic recordings at the neck

Heart rate is an important physiological parameter to assess the cardiac condition of an individual and is traditionally determined by attaching multiple electrodes on the chest of a subject to record the electrical activity of the heart. The installation and handling complexities of such systems does not prove feasible for a user to undergo a long-term monitoring in the home settings. A small-sized, battery-operated wearable monitoring device is placed on the suprasternal notch at neck to record acoustic signals containing information about breathing and cardiac sounds. The heart sounds obtained are heavily corrupted by the respiratory cycles and other external artifacts. This paper presents a novel algorithm for reliably extracting the heart rate from such acoustic recordings, keeping in mind the constraints posed by the wearable technology. The methodology constructs the Hilbert energy envelope of the signal by calculating its instantaneous characteristics to segment and classify a cardiac cycle into S1 and S2 sounds using their timing characteristics. The algorithm is tested on a dataset consisting of 13 subjects with an approximate data length of 75 hours and achieves an accuracy of 94.34%, an RMS error of 3.96 bpm and a correlation coefficient of 0.93 with reference to a commercial device in use

Comparison of System Call Representations for Intrusion Detection

Over the years, artificial neural networks have been applied successfully in many areas including IT security. Yet, neural networks can only process continuous input data. This is particularly challenging for security-related non-continuous data like system calls. This work focuses on four different options to preprocess sequences of system calls so that they can be processed by neural networks. These input options are based on one-hot encoding and learning word2vec or GloVe representations of system calls. As an additional option, we analyze if the mapping of system calls to their respective kernel modules is an adequate generalization step for (a) replacing system calls or (b) enhancing system call data with additional information regarding their context. However, when performing such preprocessing steps it is important to ensure that no relevant information is lost during the process. The overall objective of system call based intrusion detection is to categorize sequences of system calls as benign or malicious behavior. Therefore, this scenario is used to evaluate the different input options as a classification task. The results show, that each of the four different methods is a valid option when preprocessing input data, but the use of kernel modules only is not recommended because too much information is being lost during the mapping process.Comment: 12 pages, 1 figure, submitted to CISIS 201

Mucinous appendiceal adenocarcinomas: a diagnostic challenge

Mucinous appendiceal neoplasms are rare and diagnosis is often difficult as patients present with non-specific symptoms often suggestive of appendicitis only and most diagnoses are made following post-surgery histology examination. Here we present a case of a mucinous appendiceal adenocarcinoma with areas of both Low-grade Appendiceal Mucinous Neoplasm and High-grade Appendiceal Mucinous Neoplasm, in a ruptured appendix at a district general hospital. Without early detection and treatment these pathologies can lead to pseudomyxoma peritonei, a syndrome of progressive mucinous ascites. This case highlights the limitations of radiological studies, benefits of diagnostic laparoscopy and provides a rationale for removing the mesoappendix with the appendix during routine appendectomies

An economic comparison of hospital-based and community-based glaucoma clinics

INTRODUCTION: We have established one model for community care of glaucoma clinic patients. Community optometrists received training and accreditation in glaucoma care. Once qualified they alternated between running half day glaucoma clinics in their own High Street practices and assisting in a hospital-based glaucoma clinic session. This paper reports the cost of this model. METHODS: Micro-costing was undertaken for the hospital clinic. A consensus meeting was held to agree costs for community clinics involving all optometrists in the project along with representatives of the multiple chain optometry practices who had participated. Costs to patients both indirect and direct were calculated following structured interviews of 197 patients attending hospital clinics and 194 attending community clinics. RESULTS: The estimated cost per patient attendance to the hospital clinic was £63.91 and the estimated cost per attendance to the community clinic was £145.62. For patients the combined direct and indirect cost to attend the hospital clinic was £6.15 and the cost to attend the community clinic £5.91. DISCUSSION: The principal reason for the higher cost in the community clinic was higher overhead costs in the community. Re-referral to the hospital system only occurred for 9% of patients and was not a large contribution to the increased cost. Time requested to next appointment was similar for the two clinics. Sensitivity analysis shows a strong effect of increasing patients seen per clinic. It would, however, require 25 patients to be seen per clinician per day in the community in order to make the costs comparable

Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by myocardial fibrofatty replacement and an increased risk of sudden cardiac death (SCD). Originally described as a right ventricular disease, ACM is increasingly recognized as a biventricular entity. We evaluated pathological, genetic, and clinical associations in a large SCD cohort. METHODS: We investigated 5205 consecutive cases of SCD referred to a national cardiac pathology center between 1994 and 2018. Hearts and tissue blocks were examined by expert cardiac pathologists. After comprehensive histological evaluation, 202 cases (4%) were diagnosed with ACM. Of these, 15 (7%) were diagnosed antemortem with dilated cardiomyopathy (n=8) or ACM (n=7). Previous symptoms, medical history, circumstances of death, and participation in competitive sport were recorded. Postmortem genetic testing was undertaken in 24 of 202 (12%). Rare genetic variants were classified according to American College of Medical Genetics and Genomics criteria. RESULTS: Of 202 ACM decedents (35.4±13.2 years; 82% male), no previous cardiac symptoms were reported in 157 (78%). Forty-one decedents (41/202; 20%) had been participants in competitive sport. The adjusted odds of dying during physical exertion were higher in men than in women (odds ratio, 4.58; 95% CI, 1.54-13.68; P=0.006) and in competitive athletes in comparison with nonathletes (odds ratio, 16.62; 95% CI, 5.39-51.24; P<0.001). None of the decedents with an antemortem diagnosis of dilated cardiomyopathy fulfilled definite 2010 Task Force criteria. The macroscopic appearance of the heart was normal in 40 of 202 (20%) cases. There was left ventricular histopathologic involvement in 176 of 202 (87%). Isolated right ventricular disease was seen in 13%, isolated left ventricular disease in 17%, and biventricular involvement in 70%. Among whole hearts, the most common areas of fibrofatty infiltration were the left ventricular posterobasal (68%) and anterolateral walls (58%). Postmortem genetic testing yielded pathogenic variants in ACM-related genes in 6 of 24 (25%) decedents. CONCLUSIONS: SCD attributable to ACM affects men predominantly, most commonly occurring during exertion in athletic individuals in the absence of previous reported cardiac symptoms. Left ventricular involvement is observed in the vast majority of SCD cases diagnosed with ACM at autopsy. Current Task Force criteria may fail to diagnose biventricular ACM before death

Vangl2-Regulated Polarisation of Second Heart Field-Derived Cells Is Required for Outflow Tract Lengthening during Cardiac Development.

Planar cell polarity (PCP) is the mechanism by which cells orient themselves in the plane of an epithelium or during directed cell migration, and is regulated by a highly conserved signalling pathway. Mutations in the PCP gene Vangl2, as well as in other key components of the pathway, cause a spectrum of cardiac outflow tract defects. However, it is unclear why cells within the mesodermal heart tissue require PCP signalling. Using a new conditionally floxed allele we show that Vangl2 is required solely within the second heart field (SHF) to direct normal outflow tract lengthening, a process that is required for septation and normal alignment of the aorta and pulmonary trunk with the ventricular chambers. Analysis of a range of markers of polarised epithelial tissues showed that in the normal heart, undifferentiated SHF cells move from the dorsal pericardial wall into the distal outflow tract where they acquire an epithelial phenotype, before moving proximally where they differentiate into cardiomyocytes. Thus there is a transition zone in the distal outflow tract where SHF cells become more polarised, turn off progenitor markers and start to differentiate to cardiomyocytes. Membrane-bound Vangl2 marks the proximal extent of this transition zone and in the absence of Vangl2, the SHF-derived cells are abnormally polarised and disorganised. The consequent thickening, rather than lengthening, of the outflow wall leads to a shortened outflow tract. Premature down regulation of the SHF-progenitor marker Isl1 in the mutants, and accompanied premature differentiation to cardiomyocytes, suggests that the organisation of the cells within the transition zone is important for maintaining the undifferentiated phenotype. Thus, Vangl2-regulated polarisation and subsequent acquisition of an epithelial phenotype is essential to lengthen the tubular outflow vessel, a process that is essential for on-going cardiac morphogenesis

Vandetanib-eluting radiopaque beads for chemoembolization: physicochemical evaluation and biological activity of vandetanib in hypoxia.

Vandetanib-eluting radiopaque beads (VERB) have been developed for use in transarterial chemoembolization of liver tumours, with the goal of combining embolization with local delivery of antiangiogenic therapy. The objective of this study was to investigate how embolization-induced hypoxia may affect antitumoural activity of vandetanib, an inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR), in the context of hepatocellular carcinoma (HCC) treatment. We studied the effect of vandetanib on proliferation, cell cycle and apoptosis of HCC cells, in hypoxic conditions, as well as the direct effects of the beads on 3D HCC spheroids. Vandetanib suppressed proliferation and induced apoptosis of HCC cells in vitro and was equipotent in hypoxic and normoxic conditions. High degrees of apoptosis were observed among cell lines in which vandetanib suppressed ERK1/2 phosphorylation and upregulated the proapoptotic protein Bim, but this did not appear essential for vandetanib-induced cell death in all cell lines. Vandetanib also suppressed the hypoxia-induced secretion of VEGF from HCC cells and inhibited proliferation of endothelial cells. Incubation of tumour spheroids with VERB led to sustained growth inhibition equivalent to the effect of free drug. We conclude that vandetanib has both antiangiogenic and direct anticancer activity against HCC cells even in hypoxic conditions, warranting the further evaluation of VERB as novel anticancer agents

Impacts of household sources on air pollution at village and regional scales in India

Approximately 3 billion people worldwide cook with solid fuels, such as wood, charcoal, and agricultural residues. These fuels, also used for residential heating, are often combusted in inefficient devices, producing carbonaceous emissions. Between 2.6 and 3.8 million premature deaths occur as a result of exposure to fine particulate matter from the resulting household air pollution (Health Effects Institute, 2018a; World Health Organization, 2018). Household air pollution also contributes to ambient air pollution; the magnitude of this contribution is uncertain. Here, we simulate the distribution of the two major health-damaging outdoor air pollutants (PM2:5 and O3) using state-of-thescience emissions databases and atmospheric chemical transport models to estimate the impact of household combustion on ambient air quality in India. The present study focuses on New Delhi and the SOMAARTH Demographic, Development, and Environmental Surveillance Site (DDESS) in the Palwal District of Haryana, located about 80 km south of New Delhi. The DDESS covers an approximate population of 200 000 within 52 villages. The emissions inventory used in the present study was prepared based on a national inventory in India (Sharma et al., 2015, 2016), an updated residential sector inventory prepared at the University of Illinois, updated cookstove emissions factors from Fleming et al. (2018b), and PM2:5 speciation from cooking fires from Jayarathne et al. (2018). Simulation of regional air quality was carried out using the US Environmental Protection Agency Community Multiscale Air Quality modeling system (CMAQ) in conjunction with the Weather Research and Forecasting modeling system (WRF) to simulate the meteorological inputs for CMAQ, and the global chemical transport model GEOS-Chem to generate concentrations on the boundary of the computational domain. Comparisons between observed and simulated O3 and PM2:5 levels are carried out to assess overall airborne levels and to estimate the contribution of household cooking emissions