Showing papers by "Rajesh Kumar published in 2016"

Observation of Gravitational Waves from a Binary Black Hole Merger

Abstract: On September 14, 2015 at 09:50:45 UTC the two detectors of the Laser Interferometer Gravitational-Wave Observatory simultaneously observed a transient gravitational-wave signal. The signal sweeps upwards in frequency from 35 to 250 Hz with a peak gravitational-wave strain of $1.0 \times 10^{-21}$. It matches the waveform predicted by general relativity for the inspiral and merger of a pair of black holes and the ringdown of the resulting single black hole. The signal was observed with a matched-filter signal-to-noise ratio of 24 and a false alarm rate estimated to be less than 1 event per 203 000 years, equivalent to a significance greater than 5.1 {\sigma}. The source lies at a luminosity distance of $410^{+160}_{-180}$ Mpc corresponding to a redshift $z = 0.09^{+0.03}_{-0.04}$. In the source frame, the initial black hole masses are $36^{+5}_{-4} M_\odot$ and $29^{+4}_{-4} M_\odot$, and the final black hole mass is $62^{+4}_{-4} M_\odot$, with $3.0^{+0.5}_{-0.5} M_\odot c^2$ radiated in gravitational waves. All uncertainties define 90% credible intervals.These observations demonstrate the existence of binary stellar-mass black hole systems. This is the first direct detection of gravitational waves and the first observation of a binary black hole merger.

Formation of oxygen vacancies and Ti 3+ state in TiO 2 thin film and enhanced optical properties by air plasma treatment

Abstract: This is the first time we report that simply air plasma treatment can also enhances the optical absorbance and absorption region of titanium oxide (TiO2) films, while keeping them transparent. TiO2 thin films having moderate doping of Fe and Co exhibit significant enhancement in the aforementioned optical properties upon air plasma treatment. The moderate doping could facilitate the formation of charge trap centers or avoid the formation of charge recombination centers. Variation in surface species viz. Ti3+, Ti4+, O2−, oxygen vacancies, OH group and optical properties was studied using X-ray photon spectroscopy (XPS) and UV-Vis spectroscopy. The air plasma treatment caused enhanced optical absorbance and optical absorption region as revealed by the formation of Ti3+ and oxygen vacancies in the band gap of TiO2 films. The samples were treated in plasma with varying treatment time from 0 to 60 seconds. With the increasing treatment time, Ti3+ and oxygen vacancies increased in the Fe and Co doped TiO2 films leading to increased absorbance; however, the increase in optical absorption region/red shift (from 3.22 to 3.00 eV) was observed in Fe doped TiO2 films, on the contrary Co doped TiO2 films exhibited blue shift (from 3.36 to 3.62 eV) due to Burstein Moss shift.

Impact of heat stress on health and performance of dairy animals: A review

Abstract: Sustainability in livestock production system is largely affected by climate change. An imbalance between metabolic heat production inside the animal body and its dissipation to the surroundings results to heat stress (HS) under high air temperature and humid climates. The foremost reaction of animals under thermal weather is increases in respiration rate, rectal temperature and heart rate. It directly affect feed intake thereby, reduces growth rate, milk yield, reproductive performance, and even death in extreme cases. Dairy breeds are typically more sensitive to HS than meat breeds, and higher producing animals are, furthermore, susceptible since they generates more metabolic heat. HS suppresses the immune and endocrine system thereby enhances susceptibility of an animal to various diseases. Hence, sustainable dairy farming remains a vast challenge in these changing climatic conditions globally.

Multi-user medical robotic system for collaboration or training in minimally invasive surgical procedures

Abstract: A multi-user medical robotic system for collaboration or training in minimally invasive surgical procedures includes first and second master input devices, a first slave robotic mechanism, and at least one processor configured to generate a first slave command for the first slave robotic mechanism by switchably using one or both of a first command indicative of manipulation of the first master input device by a first user and a second command indicative of manipulation of the second master input device by a second user. To facilitate the collaboration or training, both first and second users communicate with each other through an audio system and see the minimally invasive surgery site on first and second displays respectively viewable by the first and second users.

Clinical neurocardiology defining the value of neuroscience-based cardiovascular therapeutics

Abstract: The autonomic nervous system regulates all aspects of normal cardiac function, and is recognized to play a critical role in the pathophysiology of many cardiovascular diseases. As such, the value of neuroscience-based cardiovascular therapeutics is increasingly evident. This White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology, pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases.

A review on synthesis, characterization, and applications of nano zero valent iron (nZVI) for environmental remediation

Abstract: The recent spark in the interest for the usage of nano zero valent iron (nZVI) as a remediation tool for contaminated land and groundwater is mainly due to its higher reactivity in comparison to micro ZVI, cost effectiveness, and potential to treat a broad range of contaminants. The authors review the recent developments and approaches made on synthesis on nZVI, strucuture and characterization of nZVI, the challenges faced in the transport of nZVI in the subsurface environment, and the augmentation of the motility of nZVI. The effective use of nZVI in remediating organic pollutants (halogenated organic compounds, pharmaceutical waste, and azo dyes) and inorganic pollutants (Ni2+, PO43−, Co2+, Cu2+) carried out in recent studies is discussed. The potential risks and limitations of this emerging nanotechnology are also addressed.

Reference ranges of handgrip strength from 125,462 healthy adults in 21 countries: a prospective urban rural epidemiologic (PURE) study.

Abstract: Background The measurement of handgrip strength (HGS) has prognostic value with respect to all-cause mortality, cardiovascular mortality and cardiovascular disease, and is an important part of the evaluation of frailty. Published reference ranges for HGS are mostly derived from Caucasian populations in high-income countries. There is a paucity of information on normative HGS values in non-Caucasian populations from low- or middle-income countries. The objective of this study was to develop reference HGS ranges for healthy adults from a broad range of ethnicities and socioeconomically diverse geographic regions. Methods HGS was measured using a Jamar dynamometer in 125,462 healthy adults aged 35-70 years from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Results HGS values differed among individuals from different geographic regions. HGS values were highest among those from Europe/North America, lowest among those from South Asia, South East Asia and Africa, and intermediate among those from China, South America, and the Middle East. Reference ranges stratified by geographic region, age, and sex are presented. These ranges varied from a median (25th–75th percentile) 50 kg (43–56 kg) in men 60 years from South East Asia. Reference ranges by ethnicity and body-mass index are also reported. Conclusions Individual HGS measurements should be interpreted using region/ethnic-specific reference ranges.

Variations in Diabetes Prevalence in Low-, Middle-, and High-Income Countries: Results From the Prospective Urban and Rural Epidemiological Study.

Abstract: OBJECTIVE The goal of this study was to assess whether diabetes prevalence varies by countries at different economic levels and whether this can be explained by known risk factors. RESEARCH DESIGN AND METHODS The prevalence of diabetes, defined as self-reported or fasting glycemia ≥7 mmol/L, was documented in 119,666 adults from three high-income (HIC), seven upper-middle-income (UMIC), four lower-middle-income (LMIC), and four low-income (LIC) countries. Relationships between diabetes and its risk factors within these country groupings were assessed using multivariable analyses. RESULTS Age- and sex-adjusted diabetes prevalences were highest in the poorer countries and lowest in the wealthiest countries (LIC 12.3%, UMIC 11.1%, LMIC 8.7%, and HIC 6.6%; P < 0.0001). In the overall population, diabetes risk was higher with a 5-year increase in age (odds ratio 1.29 [95% CI 1.28–1.31]), male sex (1.19 [1.13–1.25]), urban residency (1.24 [1.11–1.38]), low versus high education level (1.10 [1.02–1.19]), low versus high physical activity (1.28 [1.20–1.38]), family history of diabetes (3.15 [3.00–3.31]), higher waist-to-hip ratio (highest vs. lowest quartile; 3.63 [3.33–3.96]), and BMI (≥35 vs. <25 kg/m2; 2.76 [2.52–3.03]). The relationship between diabetes prevalence and both BMI and family history of diabetes differed in higher- versus lower-income country groups ( P for interaction < 0.0001). After adjustment for all risk factors and ethnicity, diabetes prevalences continued to show a gradient (LIC 14.0%, LMIC 10.1%, UMIC 10.9%, and HIC 5.6%). CONCLUSIONS Conventional risk factors do not fully account for the higher prevalence of diabetes in LIC countries. These findings suggest that other factors are responsible for the higher prevalence of diabetes in LIC countries.

A 45 nm CMOS-SOI Monolithic Photonics Platform With Bit-Statistics-Based Resonant Microring Thermal Tuning

Abstract: The microring resonator is critical for dense wavelength division multiplexed (DWDM) chip-to-chip optical I/O, enabling modulation and channel selection at the $\upmu\text{m}$ -scale suitable for a VLSI chip. Microring-based links, however, require active tuning to counteract process and thermo-optic variations. Here, we present a bit-statistical tuner that decouples tracking of optical one- and zero-levels to realize non-dc-balanced data transmission, an “eye-max”-locking controller, and self-heating cancellation without need for a high-speed sensing frontend. We implement the tuner on a 45 nm CMOS-SOI process with monolithically integrated photonic devices and circuits. The tuner consumes 0.74 mW in the logic while achieving a record 524 GHz ( $>$ 50 K temperature) tuning range at $3.8\;\upmu\text{W/GHz}$ heater efficiency. To our knowledge, this is the highest range and heater efficiency reported by an on-chip closed-loop thermal tuner to date. The tuner integrates with a 5 Gb/s 30 fJ/bit monolithic microring transmitter, achieving wavelength-lock and immunity to both tracking failures and self-heating events caused by arbitrary, non-dc-balanced bitstreams. In addition, the tuner provides critical functionality for an 11- $\lambda$ DWDM transmitter macro capable of $11\ \times\ 8$ Gb/s bandwidth on a fiber. Together with the transmitter, a 10 Gb/s on-chip monolithic optical receiver with $10^{-{\textbf{12}}}$ BER sensitivity of $9\;\upmu\text{A}$ at 10 Gb/s enables a sub-pJ/bit 5 Gb/s optical chip-to-chip link, with the bit-statistical tuner providing thermally robust microring operation.

TERT promoter mutations in melanoma survival.

Abstract: Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at-risk primary melanoma patients. In this study, we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. Tumors from 300 patients with stage I/II melanoma were sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression-free and melanoma-specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease-free and melanoma-specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease-free survival was 2.3 (95% CI 1.2-4.4) and for melanoma-specific survival 5.8 (95% CI 1.9-18.3). The effect of the mutations on melanoma-specific survival in noncarriers of variant allele of the polymorphism was significant (HR 4.5, 95% CI 1.4-15.2) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.3, 95% CI 0.1-0.9). The data in this study provide preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter.

Danger-associated peptide signaling in Arabidopsis requires clathrin.

Abstract: The Arabidopsis thaliana endogenous elicitor peptides (AtPeps) are released into the apoplast after cellular damage caused by pathogens or wounding to induce innate immunity by direct binding to the membrane-localized leucine-rich repeat receptor kinases, PEP RECEPTOR1 (PEPR1) and PEPR2. Although the PEPR-mediated signaling components and responses have been studied extensively, the contributions of the subcellular localization and dynamics of the active PEPRs remain largely unknown. We used live-cell imaging of the fluorescently labeled and bioactive pep1 to visualize the intracellular behavior of the PEPRs in the Arabidopsis root meristem. We found that AtPep1 decorated the plasma membrane (PM) in a receptor-dependent manner and cointernalized with PEPRs. Trafficking of the AtPep1-PEPR1 complexes to the vacuole required neither the trans-Golgi network/early endosome (TGN/EE)-localized vacuolar H(+)-ATPase activity nor the function of the brefeldin A-sensitive ADP-ribosylation factor-guanine exchange factors (ARF-GEFs). In addition, AtPep1 and different TGN/EE markers colocalized only rarely, implying that the intracellular route of this receptor-ligand pair is largely independent of the TGN/EE. Inducible overexpression of the Arabidopsis clathrin coat disassembly factor, Auxilin2, which inhibits clathrin-mediated endocytosis (CME), impaired the AtPep1-PEPR1 internalization and compromised AtPep1-mediated responses. Our results show that clathrin function at the PM is required to induce plant defense responses, likely through CME of cell surface-located signaling components.

Cost of Delivering Health Care Services in Public Sector Primary and Community Health Centres in North India.

Abstract: Background With the commitment of the national government to provide universal healthcare at cheap and affordable prices in India, public healthcare services are being strengthened in India. However, there is dearth of cost data for provision of health services through public system like primary & community health centres. In this study, we aim to bridge this gap in evidence by assessing the total annual and per capita cost of delivering the package of health services at PHC and CHC level. Secondly, we determined the per capita cost of delivering specific health services like cost per antenatal care visit, per institutional delivery, per outpatient consultation, per bed-day hospitalization etc. Methods We undertook economic costing of fourteen public health facilities (seven PHCs and CHCs each) in three North-Indian states viz., Haryana, Himachal Pradesh and Punjab. Bottom-up costing method was adopted for collection of data on all resources spent on delivery of health services in selected health facilities. Analysis was undertaken using a health system perspective. The joint costs like human resource, capital, and equipment were apportioned as per the time value spent on a particular service. Capital costs were discounted and annualized over the estimated life of the item. Mean annual costs and unit costs were estimated along with their 95% confidence intervals using bootstrap methodology. Results The overall annual cost of delivering services through public sector primary and community health facilities in three states of north India were INR 8.8 million (95% CI: 7,365,630–10,294,065) and INR 26.9 million (95% CI: 22,225,159.3–32,290,099.6), respectively. Human resources accounted for more than 50% of the overall costs at both the level of PHCs and CHCs. Per capita per year costs for provision of complete package of preventive, curative and promotive services at PHC and CHC were INR 170.8 (95% CI: 131.6–208.3) and INR162.1 (95% CI: 112–219.1), respectively. Conclusion The study estimates can be used for financial planning of scaling up of similar health services in the urban areas under the aegis of National Health Mission. The estimates would be also useful in undertaking equity analysis and full economic evaluations of the health systems.

Functional Imaging of Autonomic Regulation: Methods and Key Findings

Abstract: Central nervous system processing of autonomic function involves a network of regions throughout the brain which can be visualized and measured with neuroimaging techniques, notably functional magnetic resonance imaging (fMRI). The development of fMRI procedures has both confirmed and extended earlier findings from animal models, and human stroke and lesion studies. Assessments with fMRI can elucidate interactions between different central sites in regulating normal autonomic patterning, and demonstrate how disturbed systems can interact to produce aberrant regulation during autonomic challenges. Understanding autonomic dysfunction in various illnesses reveals mechanisms that potentially lead to interventions in the impairments. The objectives here are to: (1) describe the fMRI neuroimaging methodology for assessment of autonomic neural control, (2) outline the widespread, lateralized distribution of function in autonomic sites in the normal brain which includes structures from the neocortex through the medulla and cerebellum, (3) illustrate the importance of the time course of neural changes when coordinating responses, and how those patterns are impacted in conditions of sleep-disordered breathing, and (4) highlight opportunities for future research studies with emerging methodologies. Methodological considerations specific to autonomic testing include timing of challenges relative to the underlying fMRI signal, spatial resolution sufficient to identify autonomic brainstem nuclei, blood pressure, and blood oxygenation influences on the fMRI signal, and the sustained timing, often measured in minutes of challenge periods and recovery. Key findings include the lateralized nature of autonomic organization, which is reminiscent of asymmetric motor, sensory, and language pathways. Testing brain function during autonomic challenges demonstrate closely-integrated timing of responses in connected brain areas during autonomic challenges, and the involvement with brain regions mediating postural and motoric actions, including respiration, and cardiac output. The study of pathological processes associated with autonomic disruption shows susceptibilities of different brain structures to altered timing of neural function, notably in sleep disordered breathing, such as obstructive sleep apnea and congenital central hypoventilation syndrome. The cerebellum, in particular, serves coordination roles for vestibular stimuli and blood pressure changes, and shows both injury and substantially altered timing of responses to pressor challenges in sleep-disordered breathing conditions. The insights into central autonomic processing provided by neuroimaging have assisted understanding of such regulation, and may lead to new treatment options for conditions with disrupted autonomic function.

PARKIN Inactivation Links Parkinson's Disease to Melanoma.

Abstract: Background Melanoma incidence is higher in patients affected by Parkinson's disease (PD) and vice versa, but the genetic link shared by both diseases is unknown. As PARK2 is both a tumor suppressor gene and frequently mutated in young onset PD, we evaluated the role of PARK2 in melanoma predisposition and progression. Methods An in-depth PARK2 gene dosage analysis and sequencing was performed on 512 French case patients and 562 healthy control patients, as well as sporadic tumors and melanoma cell lines. The frequency of genetic alterations was compared between case patients and control patients using two-sided Fisher's exact tests and odds ratio (OR) calculations. We used western blotting to determine PARKIN expression in melanocytes and melanoma cell lines and transfection followed by clonogenic assays to evaluate the effect of PARKIN expression on cellular proliferation. All statistical tests were two-sided. Results Germline PARK2 mutations (including copy number variations, splicing, and putative deleterious missense mutations) were present in 25 case patients but only four control patients (OR = 3.95, 95% confidence interval = 1.34 to 15.75). Copy number variations (CNVs) and loss of heterozygosity were present in 60% and 74%, respectively, of primary tumors. PARKIN protein was expressed in melanocytes but not in most melanoma cell lines, and its expression decreased following melanocyte transformation by oncogenic NRAS. Re-expression of PARKIN in melanoma cell lines resulted in a drastic reduction of cell proliferation and inhibition of PARKIN in melanocytes stimulated their proliferation. Conclusion Our results show an important role for PARK2 as a tumor suppressor both in melanoma predisposition and progression, which could explain the epidemiological association of these diseases.

Cost Effectiveness of Implementing Integrated Management of Neonatal and Childhood Illnesses Program in District Faridabad, India

Abstract: Introduction Despite the evidence for preventing childhood morbidity and mortality, financial resources are cited as a constraint for Governments to scale up the key health interventions in some countries. We evaluate the cost effectiveness of implementing IMNCI program in India from a health system and societal perspective. Methods We parameterized a decision analytic model to assess incremental cost effectiveness of IMNCI program as against routine child health services for infant population at district level in India. Using a 15-years time horizon from 2007 to 2022, we populated the model using data on costs and effects as found from a cluster-randomized trial to assess effectiveness of IMNCI program in Haryana state. Effectiveness was estimated as reduction in infant illness episodes, deaths and disability adjusted life years (DALY). Incremental cost per DALY averted was used to estimate cost effectiveness of IMNCI. Future costs and effects were discounted at a rate of 3%. Probabilistic sensitivity analysis was undertaken to estimate the probability of IMNCI to be cost effective at varying willingness to pay thresholds. Results Implementation of IMNCI results in a cumulative reduction of 57384 illness episodes, 2369 deaths and 76158 DALYs among infants at district level from 2007 to 2022. Overall, from a health system perspective, IMNCI program incurs an incremental cost of USD 34.5 (INR 1554) per DALY averted, USD 34.5 (INR 1554) per life year gained, USD 1110 (INR 49963) per infant death averted. There is 90% probability for ICER to be cost effective at INR 2300 willingness to pay, which is 5.5% of India’s GDP per capita. From a societal perspective, IMNCI program incurs an additional cost of USD 24.1 (INR 1082) per DALY averted, USD 773 (INR 34799) per infant death averted and USD 26.3 (INR 1183) per illness averted in during infancy. Conclusion IMNCI program in Indian context is very cost effective and should be scaled-up as a major child survival strategy.

dbEM: A database of epigenetic modifiers curated from cancerous and normal genomes

Abstract: We have developed a database called dbEM (database of Epigenetic Modifiers) to maintain the genomic information of about 167 epigenetic modifiers/proteins, which are considered as potential cancer targets. In dbEM, modifiers are classified on functional basis and comprise of 48 histone methyl transferases, 33 chromatin remodelers and 31 histone demethylases. dbEM maintains the genomic information like mutations, copy number variation and gene expression in thousands of tumor samples, cancer cell lines and healthy samples. This information is obtained from public resources viz. COSMIC, CCLE and 1000-genome project. Gene essentiality data retrieved from COLT database further highlights the importance of various epigenetic proteins for cancer survival. We have also reported the sequence profiles, tertiary structures and post-translational modifications of these epigenetic proteins in cancer. It also contains information of 54 drug molecules against different epigenetic proteins. A wide range of tools have been integrated in dbEM e.g. Search, BLAST, Alignment and Profile based prediction. In our analysis, we found that epigenetic proteins DNMT3A, HDAC2, KDM6A and TET2 are highly mutated in variety of cancers. We are confident that dbEM will be very useful in cancer research particularly in the field of epigenetic proteins based cancer therapeutics. This database is available for public at URL: http://crdd.osdd.net/raghava/dbem .

Estimation of Tau and Phosphorylated Tau181 in Serum of Alzheimer's Disease and Mild Cognitive Impairment Patients.

Abstract: The elevated level of cerebrospinal fluid (CSF) Tau and phosphorylated Tau181 (p-Tau181) proteins are well established hallmarks of Alzheimer’s disease (AD). Elevated level of p-Tau181 can differentiate AD from other neurodegenerative disease. However, the expression level of these proteins in serum of AD patient is not well set up. This study sought to evaluate the level of Tau and p-Tau181 in serum of AD, and mild cognitive impairment (MCI) patients for an alternative approach to establish protein-based markers by convenient way. Blood samples were collected from 39 AD patients, 37 MCI patients and 37 elderly individuals as controls. The levels of Tau and p-Tau181 in the serum of the different groups were measured by label free real time Surface Plasmon Resonance technology by using specific antibodies, and were further confirmed by the conventional western blot method. An appropriate statistical analysis, including Receiver Operating Characteristic (ROC), was performed. The concentrations of serum Tau and p-Tau181 were significantly higher (p<0.00001) in AD (Tau; 47.49±9.00ng/μL, p-Tau181; 0.161±0.04 ng/μL) compared to MCI (Tau; 39.26±7.78 ng/μL, p-Tau181; 0.135±0.02 ng/μL) and were further higher compared to elderly controls (Tau; 34.92±6.58 ng/μL, p-Tau181; 0.122±0.01 ng/ μL). A significant (p<0.0001) downhill correlation was found between Tau as well as p-Tau181 levels with HMSE and MoCA score. This study for the first time reports the concentration of Tau and p-Tau181 in serum of AD and MCI patients. The cutoff values of Tau and p-Tau181 of AD and MCI patients with sensitivity and specificity reveal that serum level of these proteins can be used as a predictive marker for AD and MCI.

Disrupted functional brain network organization in patients with obstructive sleep apnea

Abstract: Author(s): Park, Bumhee; Palomares, Jose A; Woo, Mary A; Kang, Daniel W; Macey, Paul M; Yan-Go, Frisca L; Harper, Ronald M; Kumar, Rajesh | Abstract: IntroductionObstructive sleep apnea (OSA) subjects show impaired autonomic, affective, executive, sensorimotor, and cognitive functions. Brain injury in OSA subjects appears in multiple sites regulating these functions, but the integrity of functional networks within the regulatory sites remains unclear. Our aim was to examine the functional interactions and the complex network organization of these interactions across the whole brain in OSA, using regional functional connectivity (FC) and brain network topological properties.MethodsWe collected resting-state functional magnetic resonance imaging (MRI) data, using a 3.0-Tesla MRI scanner, from 69 newly diagnosed, treatment-naive, moderate-to-severe OSA (age, 48.3 ± 9.2 years; body mass index, 31 ± 6.2 kg/m(2); apnea-hypopnea index (AHI), 35.6 ± 23.3 events/h) and 82 control subjects (47.6 ± 9.1 years; body mass index, 25.1 ± 3.5 kg/m(2)). Data were analyzed to examine FC in OSA over controls as interregional correlations and brain network topological properties.ResultsObstructive sleep apnea subjects showed significantly altered FC in the cerebellar, frontal, parietal, temporal, occipital, limbic, and basal ganglia regions (FDR, P l 0.05). Entire functional brain networks in OSA subjects showed significantly less efficient integration, and their regional topological properties of functional integration and specialization characteristics also showed declined trends in areas showing altered FC, an outcome which would interfere with brain network organization (P l 0.05; 10,000 permutations). Brain sites with abnormal topological properties in OSA showed significant relationships with AHI scores.ConclusionsOur findings suggest that the dysfunction extends to resting conditions, and the altered FC and impaired network organization may underlie the impaired responses in autonomic, cognitive, and sensorimotor functions. The outcomes likely result from the prominent structural changes in both axons and nuclear structures, which occur in the condition.

TERT promoter mutations in melanoma render TERT expression dependent on MAPK pathway activation

Abstract: The mechanism of telomerase re-activation in cancer had remained elusive until the discovery of frequent mutations in the promoter of the TERT gene that encodes the catalytic reverse transcriptase subunit of telomerase. We investigated the regulation of TERT expression in melanoma cell lines and our results show that promoter mutations render TERT expression dependent on MAPK activation due to oncogenic BRAF or NRAS mutations. Mutations in the TERT promoter create binding sites for ETS transcription factors. ETS1, expressed in melanoma cell lines, undergoes activating phosphorylation by ERK at Thr38 residue as a consequence of constitutively activated MAPK pathway. We demonstrate that ETS1 binds on the mutated TERT promoter leading to the re-expression of the gene. The inhibition of ETS1 resulted in reduced TERT expression. We provide evidence that the TERT promoter mutations provide a direct link between TERT expression and MAPK pathway activation due to BRAF or NRAS mutations via the transcription factor ETS1.

Aberrant Insular Functional Network Integrity in Patients with Obstructive Sleep Apnea.

Abstract: STUDY OBJECTIVES Obstructive sleep apnea (OSA) is accompanied by tissue injury to the insular cortices, areas that regulate autonomic pain, dyspnea, and mood, all of which are affected in the syndrome. Presumably, the dysregulation of insular-related functions are mediated by aberrant functional connections with other brain regions; however, the integrity of the functional connectivity (FC) to other sites is undescribed. Our aim was to examine resting-state FC of the insular cortices to other brain areas in OSA, relative to control subjects. METHODS We collected resting-state functional magnetic resonance imaging (MRI) data from 67 newly diagnosed, treatment-naive OSA and 75 control subjects using a 3.0-Tesla MRI scanner. After standard processing, data were analyzed for the left and right insular FC. RESULTS OSA subjects showed complex aberrant insular FC to several brain regions, including frontal, parietal, cingulate, temporal, limbic, basal ganglia, thalamus, occipital, cerebellar, and brainstem regions. Areas of altered FC in OSA showed linear relationships with magnitudes of sleep related and neuropsychologic-related variables, whereas control subjects showed no such relationships with those measures. CONCLUSIONS Brain functional connections from insular sites to other brain regions in OSA subjects represent abnormal autonomic, affective, sensorimotor, and cognitive control networks that may affect both impaired parasympathetic and sympathetic interactions, as well as abnormal sensorimotor integration, affected in the condition. The functional changes likely result from the previously reported structural changes in OSA subjects, as demonstrated by diverse neuroimaging studies.

Quality of Health Management Information System for Maternal & Child Health Care in Haryana State, India

Abstract: Background Despite increasing importance being laid on use of routine data for decision making in India, it has frequently been reported to be riddled with problems. Evidence suggests lack of quality in the health management information system (HMIS), however there is no robust analysis to assess the extent of its inaccuracy. We aim to bridge this gap in evidence by assessing the extent of completeness and quality of HMIS in Haryana state of India. Methods Data on utilization of key maternal and child health (MCH) services were collected using a cross-sectional household survey from 4807 women in 209 Sub-Centre (SC) areas across all 21 districts of Haryana state. Information for same services was also recorded from HMIS records maintained by auxiliary nurse midwives (ANMs) at SCs to check under- or over-recording (Level 1 discordance). Data on utilisation of MCH services from SC ANM records, for a subset of the total women covered in the household survey, were also collected and compared with monthly reports submitted by ANMs to assess over-reporting while report preparation (Level 2 discordance) to paint the complete picture for quality and completeness of routine HMIS. Results Completeness of ANM records for various MCH services ranged from 73% for DPT1 vaccination dates to 94.6% for dates of delivery. Average completeness level for information recorded in HMIS was 88.5%. Extent of Level 1 discordance for iron-folic acid (IFA) supplementation, 3 or more ante-natal care (ANC) visits and 2 Tetanus toxoid (TT) injections was 41%, 16% and 2% respectively. In 48.2% cases, respondents from community as well as HMIS records reported at least one post-natal care (PNC) home visit by ANM. Extent of Level 2 discordance ranged from 1.6% to 6%. These figures were highest for number of women who completed IFA supplementation, contraceptive intra-uterine device insertion and provision of 2nd TT injection during ANC. Conclusions HMIS records for MCH services at sub-centre level in Haryana state were satisfactory in terms of completeness. However, there were significant differences in terms of reported and evaluated coverage of MCH services. Quality of HMIS needs to be improved in order to make it relevant for public health program planning and research.

Prioritization of anticancer drugs against a cancer using genomic features of cancer cells: A step towards personalized medicine.

Abstract: In this study, we investigated drug profile of 24 anticancer drugs tested against a large number of cell lines in order to understand the relation between drug resistance and altered genomic features of a cancer cell line. We detected frequent mutations, high expression and high copy number variations of certain genes in both drug resistant cell lines and sensitive cell lines. It was observed that a few drugs, like Panobinostat, are effective against almost all types of cell lines, whereas certain drugs are effective against only a limited type of cell lines. Tissue-specific preference of drugs was also seen where a drug is more effective against cell lines belonging to a specific tissue. Genomic features based models have been developed for each anticancer drug and achieved average correlation between predicted and actual growth inhibition of cell lines in the range of 0.43 to 0.78. We hope, our study will throw light in the field of personalized medicine, particularly in designing patient-specific anticancer drugs. In order to serve the scientific community, a webserver, CancerDP, has been developed for predicting priority/potency of an anticancer drug against a cancer cell line using its genomic features (http://crdd.osdd.net/raghava/cancerdp/).