Search

Background Cough is common in pulmonary TB and other chronic respiratory infections. Identifying features that predict whether pulmonary TB is the cause would help target appropriate individuals for rapid and cost-effective screening, potentially limiting disease progression and preventing transmission to others. Methods A systematic literature search for individual studies to answer eight key questions (KQs) was conducted according to established Chest Organization methods by using the following databases: MEDLINE via PubMed, Embase, Scopus, and the Cochrane Database of Systematic Reviews from January 1, 1984, to April 2014. Searches for KQ 1 and KQ 3 were updated in February 2016. An updated KQ 2 search was undertaken in March 2017. Results Even where TB prevalence is greatest, most individuals with cough do not have pulmonary TB. There was no evidence that 1, 3, or 4 weeks' duration were better predictors than cough lasting ≥ 2 weeks to screen for pulmonary TB. In people living with HIV (PLWHIV), screening for fever, night sweats, hemoptysis, and/or weight loss in addition to cough (any World Health Organization [WHO]-endorsed symptom) increases the diagnostic sensitivity for TB. Although the diagnostic accuracy of symptom-based screening remains low, the negative predictive value of the WHO-endorsed symptom screen in PLWHIV may help to risk-stratify individuals who are not close TB contacts and who do not require further testing for pulmonary TB in resource-limited settings. However, pregnant PLWHIV are more likely to be asymptomatic, and the WHO-endorsed symptom screen is not sensitive enough to be reliable. Combined with passive case finding (PCF), active case finding (ACF) identifies pulmonary TB cases earlier and possibly when less advanced. Whether outcomes are improved or transmission is reduced is unclear. Screening asymptomatic patients is cost-effective only in populations with a very high TB prevalence. The Xpert MTB/RIF assay on sputum is more cost-effective than clinical diagnosis. To our knowledge, no published comparative studies addressed whether the rate of cough resolution is a reliable determinant of the response to treatment or whether the rate of cough resolution was faster in the absence of cavitary lung disease. All studies on cough prevalence in Mycobacterium avium complex (MAC) lung disease, other nontuberculous mycobacterial infections, fungal lung disease, and paragonimiasis were of poor quality and were excluded from the evidence review. Conclusions On the basis of relatively few studies of fair to good quality, we conclude that most individuals at high risk and household contacts with cough ≥ 2 weeks do not have pulmonary TB, but we suggest screening them regardless of cough duration. In PLWHIV, the addition of the other WHO-endorsed symptoms increases the diagnostic sensitivity of cough. Earlier screening of patients with cough will help diagnose pulmonary TB sooner but will increase the cost of screening. The addition of ACF to PCF will increase the number of pulmonary TB cases identified. Screening asymptomatic individuals is cost-effective only in groups with a very high TB prevalence. Data are insufficient to determine whether cough resolution is delayed in individuals with cavitary lung disease or in those for whom treatment fails because of drug resistance, poor adherence, and/or drug malabsorption compared with results in other individuals with pulmonary TB. Cough is common in patients with lung infections due to MAC, other nontuberculous mycobacteria, fungal diseases, and paragonimiasis.

We have demonstrated the ability to controlled-pattern hydroxyapatite nanoparticles (nanoHA) onto the SiO2 and electrospun mat surfaces using dip-pen nanolithography (DPN). One of the keys to the success of this research was the formulation of nanoHA inks with well-defined physicochemical properties for specific use with dip-pen nanolithography. Studies on the effect of ink viscosity in terms of dispersion, stability, and accuracy of patterning determined the optimal formulation of ink as 3 w/v % nanoHA with 30-50% glycerol in isopropyl alcohol. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) were used to determine the dispersion of in solution. 30-50% glycerol solution yielded a dispersed nanoHA particles of size ~200 nm in ink. The stability of the inks evaluated by zeta-potential measurements and by turbidity (the tendency for nanoHA sedimentation over time) showed stability for the higher viscosity inks (30-50% glycerol formulated against 0% glycerol). Atomic force microscopy (AFM) and SEM were utilized to image the printed patterns on a SiO2 substrate and on an electrospun mat. The optimal ink consisted of 30% glycerol and 3 w/v % nanoHA with printed features ranging from 745 – 1175 nm on a SiO2 substrate. Additionally, nanoHA printed onto an electrospun scaffold showed DPN without fiber damage onto soft-matter. The development of a nanoHA ink for controlled DPN patterning will enable single cellular interactions to nanoscale patterning on many surfaces, including printed nanoHA-gradient-scaffold for interface tissue engineering.

A two term composite nonlinear feedback (2TCNF) control technique is developed here for nonlinear time delay systems in presence of input saturation. The proposed controller consists of two terms that are conventional composite nonlinear feedback (CNF) control and delay state control. CNF control has advantage of fast transient response and delay state control improves damping characteristics. The proposed controller thus has both these advantages and it tracks the reference smoothly. The closed loop asymptotic stability is guaranteed via Lyapunov–Krasovskii analysis. The efficiency of the proposed controller is tested on exothermic chemical reactor and validated through simulation results. Its performance is compared with the conventional CNF control. The superiority of 2TCNF is established in terms of less overshoot, fast transient response and reduced steady state error.

The focus of the paper is on exploring avenues for increasing value accruals to farmers. Basically, in the context of producers, the needfor evolution of Farmer Producer Organisations (FPOs) to reduce the exploitation by middle-men traders is apparent. The interventions being undertaken under the aegis of FPOs in different value chains and locations intervene on both forward and backward segments of the chain. Basically, the objectives of the producer companies are to: undertake various activities such as bulk purchase of inputs and delivery to farmer members; marketing of produce, grading and quality control and first level processing; procurement and maintenance of farm equipment for hiring out among farmers. The case illustrations considered in this paper present the setting in well performing FPOs offering a wide mix ofservices and earning high annual revenues as well as upcoming producer networks just graduating into providing a range of services. The benefits being accrued to member farmers range from considerable cost saving in sourcing inputs like seeds and fertilisers as well as larger net value accruals through marketing directly to end-consumers or national or global retailers. In essence, the paper validates the intervention approach of focus on FPOs as a means to provide various scale economies to small and marginal farmer stake-holders. It also reflects the option offinancing the capacity building and establishment of common facilities by such networks that agglomerate produce by means of matching grants in PPP mode. Further, it validates the need for a business development service providing platform, namely an Agri Business Promotion Facility, to provide a range of services including: the evolution of producer networks; facilitating management and technical training of such networks; providing guidance on the preparation of bankable business plans; linking networks with technology and equipment and credit related service providers; channelling links with apt markets and marketers; andproviding a range of other capacity building and networking services to consortia of farmers or FPOs to enable them to move up the value chain, eliminate rent seeking middle-men even while adding value to produce. Such interventions alone will enable the relatively deprived sections ofthe Punjab economy to integrate with the mainstream.

Gravin (AKAP12) is an A-kinase-anchoring-protein that scaffolds protein kinase A (PKA), β2-adrenergic receptor (β2-AR), protein phosphatase 2B and protein kinase C. Gravin facilitates β2-AR-dependent signal transduction through PKA to modulate cardiac excitation-contraction coupling and its removal positively affects cardiac contraction. Trabeculae from the right ventricles of gravin mutant (gravin-t/t) mice were employed for force determination. Simultaneously, corresponding intracellular Ca2+ transient ([Ca2+]i) were measured. Twitch force (Tf)-interval relationship, [Ca2+]i-interval relationship, and the rate of decay of post-extrasysolic potentiation (Rf) were also obtained. Western blot analysis were performed to correlate sarcomeric protein expression with alterations in calcium cycling between the WT and gravin-t/t hearts. Gravin-t/t muscles had similar developed force compared to WT muscles despite having lower [Ca2+]i at any given external Ca2+ concentration ([Ca2+]o). The time to peak force and peak [Ca2+]i were slower and the time to 75% relaxation was significantly prolonged in gravin-t/t muscles. Both Tf-interval and [Ca2+]i-interval relations were depressed in gravin-t/t muscles. Rf, however, did not change. Furthermore, Western blot analysis revealed decreased ryanodine receptor (RyR2) phosphorylation in gravin-t/t hearts. Gravin-t/t cardiac muscle exhibits increased force development in responsiveness to Ca2+. The Ca2+ cycling across the SR appears to be unaltered in gravin-t/t muscle. Our study suggests that gravin is an important component of cardiac contraction regulation via increasing myofilament sensitivity to calcium. Further elucidation of the mechanism can provide insights to role of gravin if any in the pathophysiology of impaired contractility.

For the first time, a series of Nitrogen-doped-ZnO nanosheet coupled with BiVO 4 (N-ZnO/BiVO 4 ) heterojunctioned photocatalysts have been synthesized. The new N-ZnO/BiVO 4 material has been prepared via a simple and effective method of precipitation followed by high temperature annealing process. The photocatalytic activities of the N-ZnO/BiVO 4 composites were evaluated for the degradation of methylene blue (MB) a common organic pollutant under visible-light irradiation. The results revealed that photocatalytic activity of the coupled system was directly influenced by the percentage amount of BiVO 4 in N-ZnO which affected the available exposed surface area for photoreactions. 30% N-ZnO/BiVO 4 system exhibited remarkable performance than 10%N-ZnO/BiVO 4 , 50%N-ZnO/BiVO 4 , and also to their pristine counterparts. The composite demonstrated the degradation efficiency of 90% in 90 min which is 1.76 times the efficiency of pure ZnO for same time duration. This pronounced photocatalytic effect is ascribed to the reduced band gap and lowered recombination rate of ZnO due to nitrogen doping and enhanced low energy charge carrier transitions between zinc interstitial defect bands, formed by the addition of BiVO 4 in N-ZnO, to the conduction band of N-ZnO at the interface. Based on the experimental results, a proposed Z-scheme mechanism for the Nitrogen-doped ZnO/BiVO 4 photocatalyst was discussed.

We present systematic investigations on the relationship between interface formation and enhanced photocatalytic activity of ZnO-BiVO4 nanocomposite based on experimental techniques supported by theoretical calculations. The interaction between ZnO (101) nanosheet and BiVO4 surface at the heterojunction was explored to study the charge transfer and separation mechanism responsible for enhanced photocatalytic response. XPS results and DFT computations mutually validate the reasonable existence of ZnO-BiVO4 interface. The nanocomposite photocatalytic activity, tested for various weight ratios, was found to be highest for ZnO-BiVO4 (1 : 1) under visible-light irradiation. Moreover, the percentage removal of MB was found to be greater than RhB for the same time duration. Steady state and time resolve photoluminescence were employed to understand the carrier lifetime and emissivity. Visible light driven high photoactivity exhibited by ZnO-BiVO4 (1 : 1) was ascribed to the formation of intermediate band and comparatively low recombination rate, which facilitates the separation of electron-hole pairs. Based on the theoretical outcome, we found that valence band maximum was occupied by Bi s orbital and conduction band minimum was occupied by Zn s orbital, which indicates the maximum electron transition from BiVO4 valence band to ZnO conduction band in ZnO-BiVO4 composite. These results demonstrated that heterojunction semiconductors are an effective strategy that can be successfully applied to develop photocatalysts that respond to visible light for organic pollutant degradation.

Aims Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins. Materials and methods MEDLINE, EMBASE, CENTRAL and PubMed databases were searched. Randomized clinical trials (RCTs) of ≥16 weeks’ duration comparing GLP-1 RAs versus basal insulins in adults with type 2 diabetes inadequately controlled with oral antihyperglycemic drugs were included. Data were extracted on the change from baseline to 26 weeks (±10 weeks) of treatment in hemoglobin A1c (HbA1c) and weight, as well as the proportion of patients experiencing hypoglycemia. Fixed-effect pairwise meta-analyses were conducted where data were available from ≥ two studies. Results Fifteen RCTs were identified and 11 meta-analysed. The once-weekly GLP-1 RAs, exenatide long acting release (LAR) and dulaglutide, led to greater, statistically significant mean HbA1c reductions versus basal insulins (exenatide: -0.31% [95% confidence interval -0.42, -0.19], dulaglutide: -0.39% [-0.49, -0.29]) whilst once-daily liraglutide and twice-daily exenatide did not (liraglutide: 0.06% [-0.06, 0.18], exenatide: 0.01% [-0.11, 0.13]). Mean weight reduction was seen with all GLP-1 RAs while mean weight gain was seen with basal insulins Interpretation of the analysis of hypoglycemia was limited by inconsistent definitions and reporting. Due to the limited number of available studies sensitivity analyses to explore heterogeneity could not be conducted. Conclusions Although weight reduction is seen with all GLP-1RA’s, only the once weekly agents, exenatide LAR and dulaglutide, demonstrate significant HbA1c reductions when compared to basal insulins.

Chlorthalidone (CTD) is more potent than hydrochlorothiazide (HCTZ) in reducing blood pressure (BP) in hypertensive patients, though both are plagued with BP response variability. However, there is a void in the literature regarding the genetic determinants contributing to the variability observed in BP response to CTD. We performed a discovery genome wide association analysis of BP response post CTD treatment in African Americans (AA) and European Americans (EA) from the Pharmacogenomic Evaluation of Antihypertensive Responses-2 (PEAR-2) study and replication in an independent cohort of AA and EA treated with HCTZ from the PEAR study, followed by a race specific meta-analysis of the two studies. Successfully replicated SNPs were further validated in beta-blocker treated participants from PEAR-2 and PEAR for opposite direction of association. The replicated and validated signals were further evaluated by protein-protein interaction network analysis. An intronic SNP rs79237970 in the WDR92 (eQTL for PPP3R1) was significantly associated with better DBP response to CTD (p = 5.76 × 10−6, β = −15.75) in the AA cohort. This SNP further replicated in PEAR (p = 0.00046, β = −9.815) with a genome wide significant meta-analysis p-value of 8.49 × 10−9. This variant was further validated for opposite association in two β-blockers treated cohorts from PEAR-2 metoprolol (p = 9.9 × 10−3, β = 7.47) and PEAR atenolol (p = 0.04, β = 4.36) for association with DBP. Studies have implicated WDR92 in coronary artery damage. PPP3R1 is the regulatory subunit of the calcineurin complex. Use of calcineurin inhibitors is associated with HTN. Studies have also shown polymorphisms in PPP3R1 to be associated with ventricular hypertrophy in AA hypertensive patients. Protein-protein interaction analysis further identified important hypertension related pathways such as inositol phosphate-mediated signaling and calcineurin-NFAT signaling cascade as important biological process associated with PPP3R1 which further strengthen the potential importance of this signal. These data collectively suggest that WDR92 and PPP3R1 are novel candidates that may help explain the genetic underpinnings of BP response of thiazide and thiazide-like diuretics and help identify the patients better suited for thiazide and thiazide-like diuretics compared to β-blockers for improved BP management. This may further help advance personalized approaches to antihypertensive therapy.

BackgroundThe association between sodium-glucose cotransporter 2 inhibitors (SGLT2i's) and lower extremity amputation is unclear.PurposeTo systematically review randomized control trials (RCTs) and observational studies quantifying risk of lower extremity amputations associated with SGLT2i use.Data sources and study selectionWe searched PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from January 2011 to February 2020 for RCTs and observational studies including lower extremity amputation outcomes for individuals with type 2 diabetes mellitus treated with SGLT2i's vs. alternative treatments or placebo.Data extraction and synthesisTwo reviewers independently extracted data.Main outcomes and measuresOur primary outcome was risk of lower limb amputation. Secondary outcomes included peripheral arterial disease, peripheral vascular disease, venous ulcerations, and diabetic foot infections. We also evaluated the risk of bias. We conducted random and fixed effects relative risk meta-analysis of RCTs.ResultsAfter screening 2,006 studies, 12 RCTs and 18 observational studies were included, of which 7 RCTs and 18 observational studies had at least one event. The random effects meta-analysis of 7 RCTs suggested the absence of a statistically significant association between SGLT2i exposure with evidence of substantial statistical heterogeneity (n = 424/23,716 vs n = 267/18,737 in controls; RR 1.28, CI's 0.93-1.76; I2 = 62.0%; p = 0.12) whereas fixed effects analysis showed an increased risk with statistical heterogeneity (RR 1.27, 1.09-1.48; I2 = 62%; p = 0.003). Subgroup analysis of canagliflozin vs placebo showed a statistically significantly increased risk in a fixed effects meta-analysis (n = 2 RCTs, RR 1.59, 1.26-2.01; I2 = 88%; p = 0.0001) whereas the meta-analysis of dapagliflozin or empagliflozin (n = 2 RCTs each) and a single RCT for ertugliflozin did not show a significantly increased risk. The findings from observational studies were too heterogeneous to be pooled in a meta-analysis and draw meaningful conclusions. Both randomized and observational studies were of generally good methodological quality.ConclusionsOverall, there was no consistent evidence of SGLT2i exposure and increased risk of amputation. The increased risk of amputation seen in the large, long-term Canagliflozin Cardiovascular Assessment Study (CANVAS) trial for canagliflozin, and select observational studies, merits continued exploration.

Background There exists a wide interindividual variability in blood pressure ( BP ) response to β 1 ‐blockers. To identify the genetic determinants of this variability, we performed a pharmacogenomic genome‐wide meta‐analysis of genetic variants influencing β 1 ‐blocker BP response. Methods and Results Genome‐wide association analysis for systolic BP and diastolic BP response to β 1 ‐blockers from 5 randomized clinical trials consisting of 1254 patients with hypertension of European ancestry were combined in meta‐analysis and single nucleotide polymorphisms (SNPs) with P −4 were tested for replication in 2 independent randomized clinical trials of β 1 ‐blocker–treated patients of European ancestry (n=1552). Regions harboring the replicated SNP s were validated in a β 1 ‐blocker–treated black cohort from 2 randomized clinical trials (n=315). A missense SNP rs28404156 in BST 1 was associated with systolic BP response to β 1 ‐blockers in the discovery meta‐analysis ( P =9.33×10 −5 , β=−3.21 mm Hg) and replicated at Bonferroni significance ( P =1.85×10 −4 , β=−4.86 mm Hg) in the replication meta‐analysis with combined meta‐analysis approaching genome‐wide significance ( P =2.18×10 −7 ). This SNP in BST 1 is in linkage disequilibrium with several SNP s with putative regulatory functions in nearby genes, including CD 38 , FBXL 5 , and FGFBP 1 , all of which have been implicated in BP regulation. SNP s in this genetic region were also associated with BP response in the black cohort. Conclusions Data from randomized clinical trials of 8 European ancestry and 2 black cohorts support the assumption that BST 1 containing locus on chromosome 4 is associated with β 1 ‐blocker BP response. Given the previous associations of this region with BP , this is a strong candidate region for future functional studies and potential use in precision medicine approaches for BP management and risk prediction.

Selection of antihypertensive treatment according to self-defined ethnicity is recommended by some guidelines but might be better guided by individual genotype rather than ethnicity or race. We compared the extent to which variation in blood pressure response across different ethnicities may be explained by genetic factors: genetically defined ancestry and gene variants at loci known to be associated with blood pressure. We analyzed data from 5 trials in which genotyping had been performed (n=4696) and in which treatment responses to β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blocker, thiazide or thiazide-like diuretic and calcium channel blocker were available. Genetically defined ancestry for proportion of African ancestry was computed using the 1000 genomes population database as a reference. Differences in response to the thiazide diuretic hydrochlorothiazide, the β-blockers atenolol and metoprolol, the angiotensin-converting enzyme inhibitor lisinopril, and the angiotensin receptor blocker candesartan were more closely associated to genetically defined ancestry than self-defined ethnicity in admixed subjects. A relatively small number of gene variants related to loci associated with drug-signaling pathways (KCNK3, SULT1C3, AMH, PDE3A, PLCE1, PRKAG2) with large effect size (-3.5 to +3.5 mm Hg difference in response per allele) and differing allele frequencies in black versus white individuals explained a large proportion of the difference in response to candesartan and hydrochlorothiazide between these groups. These findings suggest that a genomic precision medicine approach can be used to individualize antihypertensive treatment within and across populations without recourse to surrogates of genetic structure such as self-defined ethnicity.

Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the CNS. Bile acids are cholesterol metabolites that can signal through receptors on cells throughout the body, including in the CNS and the immune system. Whether bile acid metabolism is abnormal in MS is unknown. Using global and targeted metabolomic profiling, we identified lower levels of circulating bile acid metabolites in multiple cohorts of adult and pediatric patients with MS compared with controls. In white matter lesions from MS brain tissue, we noted the presence of bile acid receptors on immune and glial cells. To mechanistically examine the implications of lower levels of bile acids in MS, we studied the in vitro effects of an endogenous bile acid, tauroursodeoxycholic acid (TUDCA), on astrocyte and microglial polarization. TUDCA prevented neurotoxic (A1) polarization of astrocytes and proinflammatory polarization of microglia in a dose-dependent manner. TUDCA supplementation in experimental autoimmune encephalomyelitis reduced the severity of disease through its effects on G protein-coupled bile acid receptor 1 (GPBAR1). We demonstrate that bile acid metabolism was altered in MS and that bile acid supplementation prevented polarization of astrocytes and microglia to neurotoxic phenotypes and ameliorated neuropathology in an animal model of MS. These findings identify dysregulated bile acid metabolism as a potential therapeutic target in MS.

Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the CNS. Bile acids are cholesterol metabolites that can signal through receptors on cells throughout the body, including the CNS and immune system. Whether bile acid metabolism is abnormal in MS is unknown. Using global and targeted metabolomic profiling, we identified lower levels of circulating bile acid metabolites in multiple cohorts of adult and pediatric MS patients compared to controls. In white matter lesions from MS brain tissue, we noted the presence of bile acid receptors on immune and glial cells. To mechanistically examine the implications of lower levels of bile acids in MS, we studied the in vitro effects of an endogenous bile acid – tauroursodeoxycholic acid (TUDCA) on astrocyte and microglial polarization. TUDCA prevented neurotoxic (A1) polarization of astrocytes and pro-inflammatory polarization of microglia in a dose-dependent manner. TUDCA supplementation in experimental autoimmune encephalomyelitis reduced severity of disease, based on behavioral and pathological measures. We demonstrate that bile acid metabolism is altered in MS; bile acid supplementation prevents polarization of astrocytes and microglia to neurotoxic phenotypes and ameliorates neuropathology in an animal model of MS. These findings identify dysregulated bile acid metabolism as a potential therapeutic target in MS.

Semiconductor yield improvement and stability is becoming increasingly more difficult to achieve with decreasing technology nodes. There are many new sources, types, and mechanisms of process induced systematic defects, with a growing demand to identify and control those sources of hotspots that impact yield with the most comprehensive results, fastest time, and lowest cost. Previously there has been extensive characterization and publications on the techniques used for hotspot discovery, with little overall improvement to the flow and time to results needed to keep up with today’s fast paced development process which requires rapid results. We propose implementing new inspection and binning algorithms to the process window discovery methodology, to achieve improvements in time to results, process window qualification, and hotspot identification. These systematic defect discovery improvements enable lithography processes to be controlled and monitored more accurately and more precisely than ever before.

In this study, the behaviour of conventional concrete tapered piles subjected to lateral harmonic excitation is assessed. For a constant volume of pile material, the tapered pile is modelled in two different series. The first series is modelled with a constant pile tip diameter and the second series comprises of constant length of the pile. The response curves of the soil–pile system under horizontal vibration are obtained from three-dimensional finite element numerical simulation. The dynamic properties of the soil–pile system, i.e., the stiffness and the damping ratio are calculated from the response curves. It is observed that the tapered piles in the first series exhibit 4.14–8.87% lower resonant frequency than cylindrical piles of the same volume of pile material, whereas the tapered piles in the second series display a resonant frequency 2.95–7.69% higher than that of the cylindrical piles. Further, the resonant amplitude and frequency obtained from the finite element simulation are compared with a modified analytical solution. The resonant frequencies obtained from the finite element simulation are within an error limit of ± 0.57–10% as compared to that obtained from the analytical approach.

Osteonecrosis of the jaw (ONJ) is a rare but serious drug induced adverse event, mainly associated with the use of antiresorptive medications, such as intravenous (IV) bisphosphonates (BPs) in cancer patients. In this review, we evaluated all the pharmacogenomic association studies for ONJ published up to December 2018. To date, two SNPs (CYP2C8 rs1934951 and RBMS3 rs17024608) were identified to be associated with ONJ by two genome-wide association studies (GWAS). However, all six subsequent candidate gene studies failed to replicate these results. In addition, six discovery candidate gene studies tried to identify the genetic markers in several genes associated with bone remodeling, bone mineral density, or osteoporosis. After evaluating the results of these 6 studies, none of the SNPs was significantly associated with ONJ. Recently, two whole-exome sequencing (WES) analysis (including one from our group) were performed to identify variants associated with ONJ. So far, only our study successfully replicated discovery result indicating SIRT1 SNP rs7896005 to be associated with ONJ. However, this SNP also did not reach genome-wide significance. The major limitations of these studies include lack of replication phases and limited sample sizes. Even though some studies had larger sample sizes, they recruited healthy individuals as controls, not subjects treated with BPs. We conclude that a GWAS with a larger sample size followed by replication phase will be needed to fully investigate the pharmacogenomic markers of ONJ.

Detecting and resolving the true on-wafer-hotspot (defect) is critical to improve wafers’ yield in high volume manufacturing semiconductor foundries. Traditionally, Optical Rule Check (ORC) with computation lithography has been one of the most important techniques to flag potential failure patterns (weak points) after Optical Proximity Correction (OPC), where ORC results are fed back to the OPC team to fix the OPC solution if needed, or fed forward to Contamination Free Manufacturing (CFM) team to improve the inspection accuracy. However, as the integrated circuits process becomes more and more complex with the technology scaling, ORC alone could no longer identify the outlier-alike defects, even though it has helped in resolving most of defects on wafer. Failing to detect yield-killer defects could be due to the lack of sufficient understanding and modeling in terms of etching, CMP, as well as other inter-layer process variations. It has been a struggle for Fab to identify reasonable amount of defects scattered on wafer in order to understand defect mechanisms quickly, thus find ways to fix them in a timely manner. In this paper, we present a fast and accurate Defect Detection and Repair Flow (DDRF) with machine learning (ML) methodology to address the above issues. There are four parts in the DDRF: the first part is on the feature generation and data collection, the second on the ML model building, the third on the full-chip prediction, and the fourth on the hot-spot repair. We use limited amount of known defects found on wafer as input to train the ML model, and then apply the ML model to the full chip for prediction. The wafer verification data showed that our flow achieved more than 80% of defect hit rate with engineered feature extractions and ML model for a 7nm mask. Finally, we analyze the failing mechanism with more available defects, and are able to provide guidance to the OPC development to fix the defects by using the ML model.

Alzheimer’s disease (AD), one of the most common cause of dementia, is a complex neurodegenerative disease marked by amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles. Genome-wide association studies have identified rare variants of genes that implicate novel biological underpinnings of AD, unearthing untapped insights into modulation of innate immune pathways. Recent studies have implicated crucial functions of microglia (brain’s resident immune cells) clustering around Aβ plaques, such as plaque compaction and containment, suggesting a beneficial impact on limiting the extent of neuronal damage. In order to test this hypothesis, extraction of neuronal damage characteristics in correlation with microglia coverage is required on a single plaque level. We utilized immunohistochemistry and confocal microscopy to collect 3D image data sets from an AD mouse model. For the quantitative correlative assessment of the heterogeneity of microglia clustering and plaque-associated neuronal damage, we developed a multi-step image analysis pipeline consisting of (a) U-Net based automated region of interest (ROI) detection algorithm (96 % true positive rate), (b) FIJI-based custom-built image profiling tool that creates biologically meaningful image features from ROIs (plaques), and (c) Spotfire-based data visualization dashboard. Our proof-of-concept data set shows that plaque-associated microglia clustering correlates with lower neuronal damage in a disease stage and plaque size-dependent manner. This novel platform has validated our working hypothesis on protective functions of microglia during AD pathology. Future applications of the plaque profiling pipeline will enable unbiased quantitative assessment of potential neuroprotective effects by pharmacological or genetic interventions in preclinical AD models with amyloid pathology.

European Americans (EA) have a better antihypertensive response to β-blockers when compared with African Americans, albeit with some variability. We undertook a genomewide association study to elucidate the underlying genetic determinants in EA contributing to this variability in blood pressure (BP) response. A discovery genomewide association study of change in BP post-metoprolol treatment was performed in EA participants (n = 201) from the Pharmacogenomic Evaluation of Antihypertensive Responses-2 (PEAR-2) study and tested for replication in the atenolol-treated EA from the PEAR study (n = 233). Rs294610 in the FGD5, which encodes for FYVE, RhoGEF and PH Domain Containing 5, (expression quantitative trait loci for FGD5 in the small intestine) was significantly associated with increased diastolic BP response to β-blockers in the PEAR-2 study (P = 3.41 × 10-6 , β = -2.70) and replicated (P = 0.01, β = -1.17) in the PEAR study. Post-meta-analysis of these studies, an additional single nucleotide polymorphism rs45545233 in the SLC4A1, encoding for Solute Carrier Family 4 Member 1, (expression quantitative trait loci for dual specificity phosphatase 3 in the artery tibial) was identified that was significantly associated with a poor response to β-blockers (P = 3.43 × 10-6 , β = 4.57) and was replicated in the atenolol add-on cohort (P = 0.007, β = 4.97). We identified variants in FGD5 and SLC4A1, which have been previously cited as candidate genes for hypertension, to be associated with a β-blocker BP response in EA. Further elucidation is warranted of the underlying mechanisms of these variants and genes by which they influence the BP response to β-blockers.

One serious problem that all the developing nations are facing today is injuries and death of animals due to road accidents. Report says that, there are around 300,000 collisions per year. However, many of the databases exclude accidents that have vehicle damage less than $1,000 (https://apiar.org.au/wpcontent/uploads/2017/07/23_APJCECT_ICT-268-281.Pdf, [1]). Accidents lead to the reduction in wildlife. Eventually, this may lead to reduction and endangered of rare species. A system has to be designed to overcome this problem. In this paper, the problem is addressed by focusing on designing an IoT-based system which will perform two functions one is alerting the driver whenever an animal is nearer to the vehicle and the second one is alerting the driver whenever he exceeds the speed limit, especially in the forest region.

Importance The National Action Plan for Adverse Drug Event (ADE) Prevention identified 3 high-priority, high-risk drug classes as targets for reducing the risk of drug-related injuries: anticoagulants, diabetes agents, and opioids. Objective To determine whether a multifaceted clinical pharmacist intervention improves medication safety for patients who are discharged from the hospital and prescribed medications within 1 or more of these high-risk drug classes. Design, Setting, and Participants This randomized clinical trial was conducted at a large multidisciplinary group practice in Massachusetts and included patients 50 years or older who were discharged from the hospital and prescribed at least 1 high-risk medication. Participants were enrolled into the trial from June 2016 through September 2018. Interventions The pharmacist-directed intervention included an in-home assessment by a clinical pharmacist, evidence-based educational resources, communication with the primary care team, and telephone follow-up. Participants in the control group were provided educational materials via mail. Main Outcomes and Measures The study assessed 2 outcomes over a 45-day posthospital discharge period: (1) adverse drug-related incidents and (2) a subset defined as clinically important medication errors, which included preventable or ameliorable ADEs and potential ADEs (ie, medication-related errors that may not yet have caused injury to a patient, but have the potential to cause future harm if not addressed). Clinically important medication errors were the primary study outcome. Results There were 361 participants (mean [SD] age, 68.7 [9.3] years; 177 women [49.0%]; 319 White [88.4%] and 8 Black individuals [2.2%]). Of these, 180 (49.9%) were randomly assigned to the intervention group and 181 (50.1%) to the control group. Among all participants, 100 (27.7%) experienced 1 or more adverse drug-related incidents, and 65 (18%) experienced 1 or more clinically important medication errors. There were 81 adverse drug-related incidents identified in the intervention group and 72 in the control group. There were 44 clinically important medication errors in the intervention group and 45 in the control group. The intervention did not significantly alter the per-patient rate of adverse drug-related incidents (unadjusted incidence rate ratio, 1.13; 95% CI, 0.83-1.56) or clinically important medication errors (unadjusted incidence rate ratio, 0.99; 95% CI, 0.65-1.49). Conclusions and Relevance In this randomized clinical trial, there was not an observed lower rate of adverse drug-related incidents or clinically important medication errors during the posthospitalization period that was associated with a clinical pharmacist intervention. However, there were study recruitment challenges and lower than expected numbers of events among the study population. Trial Registration ClinicalTrials.gov Identifier:NCT02781662

Background: As per the World Health Organization Global Tuberculosis (TB) Report 2019, there were an estimated 10.0 million new TB cases worldwide in 2018, with India (27%) having the maximum burden of the disease. Drug-induced liver injury (DILI) due to antitubercular treatment (ATT) is a serious adverse effect and a major cause of discontinuation of ATT, leading to increased drug resistance, morbidity, and mortality. Methodology: This was an observational study that was conducted at a tertiary care center in South Maharashtra having a dedicated TB nodal center. All newly detected cases of pulmonary and extrapulmonary TB and cases of TB after relapse/failure/treatment after default, who reported to this nodal center from January 2019 to June 2019 and in whom Category 1 and Category 2 ATT was started as per the Revised National Tuberculosis Programme protocol, were enrolled in this study. Results: Out of 100 enrolled patients, 10 (10%) were diagnosed to have ATT-induced DILI, which is concordant with other studies. No deaths were recorded. However, there was no statistically significant difference between male and female patients who developed DILI (12% males vs. 8% females). No correlation was found with body mass index or alcohol consumption. Conclusion: A fine balance should be struck between unnecessary discontinuation of ATT and continued safe treatment. Patient and staff education, careful selection of regimen, and close monitoring of risk factors will minimize cases of DILI.

Introduction: Rituximab is slowly getting recognized as a promising steroid-sparing agent in the treatment of moderate to severe cases of pemphigus vulgaris (PV). We evaluated and compared the effectiveness, safety, and cost of therapy of rituximab versus dexamethasone cyclophosphamide pulse (DCP) in Indian patients with PV. Materials and Methods: It is a retrospective data analysis, from the Immunobullous disease clinic in a tertiary centre of eastern India, of management of PV. In our institute we use either rituximab or DCP for the management of moderate to severe cases of PV, depending on that we retrospectively divided the treated cases of PV in two groups. Patients who were treated with rheumatoid arthritis (RA) protocol of rituximab were considered to be group 1. Patients who were treated with DCP were included in group 2. Response was assessed by pemphigus area, and activity score (PAAS), Dermatology life quality index (DLQI); photographic documentation, and blood parameters were monitored. Results: Both groups showed significant improvement in PAAS and DLQI, the improvement was faster and well sustained in the rituximab group. In terms of safety and development of new vesicles, rituximab had a better profile with only 1 patient having adverse effects and none with new vesicles as compared to DCP (3 had adverse effects and 2 developed new vesicles). Conclusions: Rituximab offers the advantage of early and prolonged remission, lesser adverse effects, better effectiveness, less risk of relapses, faster improvement of PAAS, and DLQI. Though rituximab is an expensive drug, but on evaluating the cost of whole therapy, it was seen that rituximab infusions are actually cheaper compared to DCP pulse. We suggest, rituximab can be used as the first-line of therapy for pemphigus vulgaris in the Indian context.

Summary Given the conflicting evidence regarding the association between exogenous testosterone and cardiovascular events, we systematically assessed published systematic reviews for evidence of the association between exogenous testosterone and cardiovascular events. We searched PubMed, MEDLINE, Embase, Cochrane Collaboration Clinical Trials, ClinicalTrials.gov, and the US Food and Drug Administration website for systematic reviews of randomised controlled trials published up to July 19, 2016. Two independent reviewers screened 954 full texts from 29 335 abstracts to identify systematic reviews of randomised controlled trials in which the cardiovascular effects of exogenous testosterone on men aged 18 years or older were examined. We extracted data for study characteristics, analytic methods, and key findings, and applied the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist to assess methodological quality of each review. Our primary outcome measure was the direction and magnitude of association between exogenous testosterone and cardiovascular events. We identified seven reviews and meta-analyses, which had substantial clinical heterogeneity, differing statistical methods, and variable methodological quality and quality of data abstraction. AMSTAR scores ranged from 3 to 9 out of 11. Six systematic reviews that each included a meta-analysis showed no significant association between exogenous testosterone and cardiovascular events, with summary estimates ranging from 1·07 to 1·82 and imprecise confidence intervals. Two of these six meta-analyses showed increased risk in subgroup analyses of oral testosterone and men aged 65 years or older during their first treatment year. One meta-analysis showed a significant association between exogenous testosterone and cardiovascular events, in men aged 18 years or older generally, with a summary estimate of 1·54 (95% CI 1·09–2·18). Our optimal information size analysis showed that any randomised controlled trial aiming to detect a true difference in cardiovascular risk between treatment groups receiving exogenous testosterone and their controls (with a two-sided p value of 0·05 and a power of 80%) would require at least 17 664 participants in each trial group. Therefore, given the challenge of adequately powering clinical trials for rare outcomes, rigorous observational studies are needed to clarify the association between testosterone-replacement therapy and major adverse cardiovascular outcomes.

Objectives To describe challenges and make recommendations for researchers in how they select evidence to quantitatively assess a prescription drug's benefits and harms. Study Design and Setting These challenges and recommendations are based on our recent experience conducting a benefit-harm assessment for the prescription drug roflumilast. We considered the selection of evidence to quantify (1) the drug's treatment effects in patients, (2) the patient population's baseline risks for beneficial and harmful outcomes without treatment, and (3) the patient population's preferences for these beneficial effects and harms. These are fundamental steps for most benefit-harm assessment methods. Results We identify critical issues in selecting evidence for each of these steps. We justify in particular the need to incorporate (1) clinical trials for the drug's specific treatment effect; (2) observational studies with the most valid, precise, and applicable effect estimates for the baseline risk; and (3) flexible weighting approaches for balancing the drug benefits and harms. Conclusion We identify challenges and make recommendations for selecting evidence at the critical steps in a prescription drug's benefit-harm assessment. Our findings should assist other researchers conducting these assessments for prescription drugs, which could help regulators, medical professionals, and patients make better decisions about prescription drug use.

Little research exists on social isolation and health among widows despite their marginalization in South Asia. Using a conceptual framework that delineates distinct forms of social support, our results provide a preliminary analysis of the role social support plays in the well-being of Nepali widows. Between 2011 and 2012, we conducted 42 in-depth interviews in the Kathmandu valley and Surkhet district. Low social support was a common theme, principally lacking in the domains of emotional and instrumental support and was described as increasing women's vulnerability to mistreatment and economic insecurity. Policies and programs that foster these types of support may have positive effects on widows' well-being.

Background: Carfilzomib (CFZ), a proteasome inhibitor used to treat multiple myeloma (MM), has been associated with risk for cardiotoxicity including heart failure (HF). There is a lack of data on the mechanism underlying CFZ-induced cardiotoxicity. Our study aims to better understand molecular mechanisms of CFZ-related cardiotoxicity by determining the differential expression of circulating miRNAs and proteins in MM patients. Methods: Plasma samples were collected from 13 MM patients after treated with CFZ (including 7 with cardiotoxicity and 6 with no cardiotoxicity) at the University of Florida Health Cancer Center. TaqMan OpenArray Human MicroRNA Panel containing 754 human miRNA was used for miRNA analysis, and iTRAQ analysis on LC/MS/MS platforms was used for global proteomic profiling. Results: The overall mean age was 61 and 38.5% were men. A total of 374 proteins were identified and 57 were differentially expressed between cardiotoxicity and non-cardiotoxicity groups (false discovery rate Conclusion: These findings suggest that CFZ may induce cardiac dysfunction via increasing CFD activity that is regulated by miR-17, leading to activation of the complement system. Dysregulation in components of the AP of complement activation could impact the diastolic dysfunction associated with HF progression. Citation Format: Marwa Tantawy, Lakshmi Manasa Chekka, Taimour Langaee, Timothy J Garrett, Michael Fradley, Robert Frank Cornell, Rachid C. Baz, Sonal Singh, Lihui Yuan, Chintan P. Shah, Nida Waheed, Carl J. Pepine, Jan S. Moreb, Yan Gong. Differential expressions of miR-17 and complement factor D in carfilzomib-related cardiotoxicity in multiple myeloma patients: Results of microRNA array and proteomics integrated analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3694.

In this study, the dynamic response of a concrete-filled tapered Fiber Reinforced polymer (FRP) tube pile, embedded in a transversely isotropic viscoelastic medium, undergoing axial vibration is investigated. The soil adjacent to the pile comprises of an inner nonlinear zone and an outer linear viscoelastic zone. The tapered pile is discretized into small elements, and the displacements and stress compatibilities are reinforced for each element. The interface characteristics and the response of concrete confined with FRP are identified using the collected database of reported test results. An illustration is described to calculate the vertical dynamic response of concrete-filled FRP piles. Parametric estimations of the effects of the taper angle of the pile, degree of transverse isotropy, confining mechanism, and the confining material type are carried out. It is observed that the composite pile comprising of concrete confined with a tube, exhibits resonant amplitude about 4.5% higher, and resonant frequency about 5% higher than the composite pile with concrete confined with wrapping technique. For concrete-filled tapered FRP tube pile with a taper angle of 0.71° the resonant frequency is 19% higher than the resonant frequency of the straight-sided concrete-filled FRP piles.

In this study, the photocatalytic properties of graphitic carbon nitride (g-C3N4) and strategically developed acid-etched template free graphitic carbon nitride (Tg-C3N4) photocatalyst on cationic viz. Methylene blue (MB), Rhodamine B (RhB) and anionic viz. Methyl orange (MO) and Congo red (CR) dyes have been compared for the first time. g-C3N4 was prepared from melamine at 550 °C using thermal condensation method and Tg-C3N4 by acid-etched template free method through exfoliation of bulk g-C3N4 using ternary mixture of H2SO4-HNO3 (1:1) ratio with H2O2. The photocatalysts were characterized by XRD, FTIR, RAMAN, TRPL, FESEM, BET, Zeta potential, UV–Vis and XPS. The specific surface area was found to be improved from 11.12 m2/g to 17.05 m2/g and zeta value shifted from 0.53 mV to 6.74 mV in Tg-C3N4 as compared to g-C3N4. The enhanced photodegradation efficiency and fast reaction kinetics of Tg-C3N4 as compared to g-C3N4 was attributed to large specific surface area, high positive zeta potential, reduced bandgap and lower electron-hole recombination rate. The effect of different pH, scavengers, reusability, durability and stability of Tg-C3N4 was also checked.

Background: In the recent years, the frequency, severity, clinical characteristics, treatment response, and relapse rate of dermatophytosis have dramatically changed in India. Given the surge in dermatophytosis, we had undertaken a study to isolate and identify the common species causing dermatophyte infection and to know the in vitro efficacy of the common antifungals against them. Materials and Methods: A total of 103 new cases that were not on any treatment for the past 3 months were included. Skin scrapings were collected for direct microscopic examination and for fungal culture in Sabouraud 4% dextrose agar (SDA) with chloramphenicol and cycloheximide slant tubes, and dermatophyte test media. Fungi were identified on the basis of their macroscopic and microscopic features with the help of lactophenol cotton blue staining and urease test. Also, the drug sensitivity of the dermatophytes was tested with the common antifungals. Results: Of the 55 cases (53.4%) that were positive for dermatophytes in the culture, 29 showed possible contamination. Trichophyton was the predominant organism (49 cases) with T. verrucosum being the commonest species (26 cases), followed by T. rubrum (15 patients), and T. mentagrophytes (8 cases). All species of Trichophyton were found to be most sensitive to itraconazole amongst systemic antifungals and luliconazole amongst topical antifungals. Conclusion: This study concluded that the causative agent for the dermatophytosis was changing in India and in our subset, T. verrucosum caused the maximum number of infections. Itraconazole and luliconazole had the highest sensitivity amongst systemic and topical antifungals, respectively. It also showed that terbinafine had comparatively less sensitivity to most organisms.

ObjectivesBone stress injuries (BSI) are common in runners of both sexes. The purpose of this study was to determine if a modified Female Athlete Triad Cumulative Risk Assessment tool would predict BSI in male distance runners.Methods156 male runners at two collegiate programmes were studied using mixed retrospective and prospective design for a total of 7 years. Point values were assigned using risk assessment categories including low energy availability, low body mass index (BMI), low bone mineral density (BMD) and prior BSI. The outcome was subsequent development of BSI. Statistical models used a mixed effects Poisson regression model with pResults42/156 runners (27%) sustained 61 BSIs over an average 1.9 years of follow-up. In the baseline risk factor model, each 1 point increase in prior BSI score was associated with a 57% increased risk for prospective BSI (p=0.0042) and each 1 point increase in cumulative risk score was associated with a 37% increase in prospective BSI risk (p=0.0079). In the longitudinal model, each 1 point increase in cumulative risk score was associated with a 27% increase in prospective BSI risk (p=0.05). BMI (rate ratio (RR)=1.91, p=0.11) and BMD (RR=1.58, p=0.19) risk scores were not associated with BSI.ConclusionA modified cumulative risk assessment tool may help identify male runners at elevated risk for BSI. Identifying risk factors may guide treatment and prevention strategies.

This study obtains a three-dimensional unified peak strength expression for confined concrete from the reported experimental results of circular concrete columns confined with different fib...

Background To examine age-specific differences in the frequency and impact of cardiac and non-cardiac conditions among patients aged 65 years and older hospitalized with acute myocardial infarction (AMI). Methods Study population consisted of 3863 adults hospitalized with AMI at 11 medical centers in central Massachusetts on a biennial basis between 2001 and 2011. The presence of 11 chronic conditions (five cardiac and six non-cardiac) was based on the review of hospital medical records. Results Participants' median age was 79 years, 49% were men, and had an average of three chronic conditions (average of cardiac conditions: 2.6 and average of non-cardiac conditions: 1.0). Approximately one in every two patients presented with two or more cardiac related conditions whereas one in every three patients presented with two or more non-cardiac related conditions. The most prevalent chronic conditions in our study population were hypertension, diabetes, heart failure, chronic kidney disease, and peripheral vascular disease. Patients across all age groups with a greater number of previously diagnosed cardiac or non-cardiac conditions were at higher risk for developing important clinical complications or dying during hospitalization as compared to those with 0–1 condition. Conclusions The prevalence of multimorbidity among older adults hospitalized with AMI is high and associated with worse outcomes that should be considered in the management of this vulnerable population.

BackgroundThe influence of direct-acting antiviral (DAA) therapy for chronic hepatitis C virus on the risk of hepatocellular carcinoma (HCC) is conflicting.MethodsWe conducted a systematic review and meta-analysis to determine the incidence or recurrence of HCC associated with oral DAA therapy. We searched PubMed, Scopus, Embase from inception to August 2017 to identify observational studies reporting on HCC among patients treated with DAAs. Two independent reviewers extracted data and assessed the risk of bias. Data were pooled by random-effects model. The primary outcome was the proportion of participants with incidence or recurrence of HCC (PROSPERO number CRD42017057040).ResultsAfter reviewing 2080 citations, we included 8 controlled studies and 36 uncontrolled studies. The pooled proportion for incident HCC was 1.5 % (95% CI 1.0% to 2.1%; I2=90.1%; n= 542/39 145) from 18 uncontrolled studies and 3.3% (95% CI 1.2% to 9%; I2 =96%; n=109/6909) from 5 controlled studies, respectively. The pooled proportion for recurrent HCC was 16.7% (95% CI 10.2% to 26%; I2=84.8%; n=136/867) from 12 uncontrolled studies and 20.1% (95% CI 5.5% to 52.1%; I2=87.5%; n=36/225) from 3 controlled studies, respectively. There was no statistically significant effect on the risk of recurrent HCC (OR 0.50, 95%CI 0.16 to 1.59; I2 =73.4%) in a meta-analysis of three studies.ConclusionsOur findings show low proportion of incident HCC, but high proportion of recurrent HCC on treatment with DAAs. Continued active surveillance for HCC after treatment with DAAs remains prudent.

Background Violent attacks on and interferences with hospitals, ambulances, health workers, and patients during conflict destroy vital health services during a time when they are most needed and undermine the long-term capacity of the health system. In Syria, such attacks have been frequent and intense and represent grave violations of the Geneva Conventions, but the number reported has varied considerably. A systematic mechanism to document these attacks could assist in designing more protection strategies and play a critical role in influencing policy, promoting justice, and addressing the health needs of the population. Methods and findings We developed a mobile data collection questionnaire to collect data on incidents of attacks on healthcare directly from the field. Data collectors from the Syrian American Medical Society (SAMS), using the tool or a text messaging system, recorded information on incidents across four of Syria’s northern governorates (Aleppo, Idleb, Hama, and Homs) from January 1, 2016, to December 31, 2016. SAMS recorded a total of 200 attacks on healthcare in 2016, 102 of them using the mobile data collection tool. Direct attacks on health facilities comprised the majority of attacks recorded (88.0%; n = 176). One hundred and twelve healthcare staff and 185 patients were killed in these incidents. Thirty-five percent of the facilities were attacked more than once over the data collection period; hospitals were significantly more likely to be attacked more than once compared to clinics and other types of healthcare facilities. Aerial bombs were used in the overwhelming majority of cases (91.5%). We also compared the SAMS data to a separate database developed by Physicians for Human Rights (PHR) based on media reports and matched the incidents to compare the results from the two methods (this analysis was limited to incidents at health facilities). Among 90 relevant incidents verified by PHR and 177 by SAMS, there were 60 that could be matched to each other, highlighting the differences in results from the two methods. This study is limited by the complexities of data collection in a conflict setting, only partial use of the standardized reporting tool, and the fact that limited accessibility of some health facilities and workers and may be biased towards the reporting of attacks on larger or more visible health facilities. Conclusions The use of field data collectors and use of consistent definitions can play an important role in the tracking incidents of attacks on health services. A mobile systematic data collection tool can complement other methods for tracking incidents of attacks on healthcare and ensure the collection of detailed information about each attack that may assist in better advocacy, programs, and accountability but can be practically challenging. Comparing attacks between SAMS and PHR suggests that there may have been significantly more attacks than previously captured by any one methodology. This scale of attacks suggests that targeting of healthcare in Syria is systematic and highlights the failure of condemnation by the international community and medical groups working in Syria of such attacks to stop them.

Background Systematic reviews should provide trustworthy guidance to decision-makers, but their credibility is challenged by the selective reporting of trial results and outcomes. Some trials are not published, and even among clinical trials that are published partially (e.g., as conference abstracts), many are never published in full. Although there are many potential sources of published and unpublished data for systematic reviews, there are no established methods for choosing among multiple reports or data sources about the same trial. Methods We will conduct systematic reviews of the effectiveness and safety of two interventions following the Institute of Medicine (IOM) guidelines: (1) gabapentin for neuropathic pain and (2) quetiapine for bipolar depression. For the review of gabapentin, we will include adult participants with neuropathic pain who do not require ventilator support. For the review of quetiapine, we will include adult participants with acute bipolar depression (excluding mixed or rapid cycling episodes). We will compare these drugs (used alone or in combination with other interventions) with placebo or with the same intervention alone; direct comparisons with other medications will be excluded. For each review, we will conduct highly sensitive electronic searches, and the results of the searches will be assessed by two independent reviewers. Outcomes, study characteristics, and risk of bias ratings will be extracted from multiple reports by two individuals working independently, stored in a publicly available database (Systematic Review Data Repository) and analyzed using commonly available statistical software. In each review, we will conduct a series of meta-analyses using data from different sources to determine how the results are affected by the inclusion of data from multiple published sources (e.g., journal articles and conference abstracts) as well as unpublished aggregate data (e.g., “clinical study reports”) and individual participant data (IPD). We will identify patient-centered outcomes in each report and identify differences in the reporting of these outcomes across sources. Systematic review registration CRD42015014037, CRD42015014038

Mobile Technology is the most popular and widely used media of communication and covers all the wireless portable electronic devices used to perform multiple tasks. Mobile Technology allows users to make voice calls, send text messages and run applications. Apart from talking, it has provided a wireless connection to any part of the globe to make business deals, payments, shopping, all in consumer's hand. Internet access through mobile has been on the increase as it is convenient and cost effective. Mobile Technology is very useful for university libraries as the younger generation are mostly its clientele. It is an asset for university libraries to provide innovative services. The present study is a case study of Maharaja Jiwaji Rao library, Vikram University, Ujjain to trace out the use of mobile technology to provide online information access and communication. The paper concludes with the need of providing mobile services to users to keep them constantly connected to data and resources and also always to be connected with one another.