Dispatch: distributed peer-to-peer simulations

Recently there has been an increasing demand for efficient mechanisms of carrying out computations that exhibit coarse grained parallelism. Examples of this class of problems include simulations involving Monte Carlo methods, computations where numerous, similar but independent, tasks are performed to solve a large problem or any solution which relies on ensemble averages where a simulation is run under a variety of initial conditions which are then combined to form the result. With the ever increasing complexity of such applications, large amounts of computational power are required over a long period of time. Economic constraints entail deploying specialized hardware to satisfy this ever increasing computing power. We address this issue in Dispatch, a peer-to-peer framework for sharing computational power. In contrast to grid computing and other institution-based CPU sharing systems, Dispatch targets an open environment, one that is accessible to all the users and does not require any sort of membership or accounts, i.e. any machine connected to the Internet can be the part of framework. Dispatch allows dynamic and decentralized organization of these computational resources. It empowers users to utilize heterogeneous computational resources spread across geographic and administrative boundaries to run their tasks in parallel. As a first step, we address a number of challenging issues involved in designing such distributed systems. Some of these issues are forming a decentralized and scalable network of computational resources, finding sufficient number of idle CPUs in the network for participants, allocating simulation tasks in an optimal manner so as to reduce the computation time, allowing new participants to join the system and run their task irrespective of their geographical location and facilitating users to interact with their tasks (pausing, resuming, stopping) in real time and implementing security features for preventing malicious users from compromising the network and remote machines. As a second step, we evaluate the performance of Dispatch on a large-scale network consisting of 10−130 machines. For one particular simulation, we were able to achieve up to 1500 million iterations per second as compared to 10 million iterations per second on one machine. We also test Dispatch over a wide-area network where it is deployed on machines that are geographically apart and belong to different domains

All polyethylene tibia - results of functional and radiological outcome at 5 years follow-up

Background: Earlier, all-polyethylene tibial (APT) components were the only option available for TKA. APT components improved over years and have shown results similar or superior to MBT components with respect to survivorship and rate of complications. This study aimed to assess the functional and radiological outcome of TKA with APT components with 5 years follow-up.Methods: This longitudinal study was conducted in a tertiary care center in Mumbai in year 2018. All patients who underwent TKA with APT components during the year 2012 were included in the study. Total of 147 knees were operated in 120 patients. Ninty patients (111 knees) followed up at 5 years. Preoperative and postoperative assessment of patients was done for function, pain and radiological outcome. Functional scores used were Knee society score, WOMAC osteoarthritis index, Bristol score and Oxford knee score. Visual analogue scale (VAS) score was used for pain assessment. Pre and postoperative X-rays were done and component alignment angles (α, β, γ and δ) were calculated.Results: Statistically significant difference was found in pre and postoperative values of VAS score, knee society score, WOMAC osteoarthritis index, Bristol score and Oxford knee score (p value <0.001). Component alignment angles were found to be same pre and postoperatively. None of the patients had radiologic evidence of loosening of implants.Conclusions: APT components have good to excellent functional outcome and good radiological outcome at 5 years. They are safe in view of radiologic component migration at 5-year follow-up

From Unstable Contacts to Stable Control: A Deep Learning Paradigm for HD-sEMG in Neurorobotics

In the past decade, there has been significant advancement in designing wearable neural interfaces for controlling neurorobotic systems, particularly bionic limbs. These interfaces function by decoding signals captured non-invasively from the skin's surface. Portable high-density surface electromyography (HD-sEMG) modules combined with deep learning decoding have attracted interest by achieving excellent gesture prediction and myoelectric control of prosthetic systems and neurorobots. However, factors like pixel-shape electrode size and unstable skin contact make HD-sEMG susceptible to pixel electrode drops. The sparse electrode-skin disconnections rooted in issues such as low adhesion, sweating, hair blockage, and skin stretch challenge the reliability and scalability of these modules as the perception unit for neurorobotic systems. This paper proposes a novel deep-learning model providing resiliency for HD-sEMG modules, which can be used in the wearable interfaces of neurorobots. The proposed 3D Dilated Efficient CapsNet model trains on an augmented input space to computationally `force' the network to learn channel dropout variations and thus learn robustness to channel dropout. The proposed framework maintained high performance under a sensor dropout reliability study conducted. Results show conventional models' performance significantly degrades with dropout and is recovered using the proposed architecture and the training paradigm

Prevalence, pattern and perceptions of self-medication in medical students

Background: The use of self-medication is highly prevalent in the community more so amongst the medical students. Self-medication can be defined as the use of drugs to treat self-diagnosed disorders or symptoms, or the intermittent or continued use of a prescribed drug for chronic or recurrent disease or symptoms.Aims and Objectives: To study the prevalence and pattern of use of self-medication among medical students from first year to internship.Methods: This cross sectional study was carried out among under graduate medical students including interns of Smt. NHL Municipal Medical College, Ahmedabad during the period of March 2010 to May 2010. Results: Out of 747 students and interns enrolled, 685 responded (91.7%). Out of 685 respondents 564 (82.3%) reported self-medication within one year of recall period. Most common conditions/symptoms for self-medication in students were fever (72.7%), headache (69.1%), upper respiratory tract infections (64.1%) followed by others like body-ache, abdominal pain, diarrhoea etc. Over the counter drugs (84.2%) was the most common category of drugs used by all the students except first year students who used prescription only drugs more frequently (48.5%). Herbal and Ayurvedic drugs were also used as self-medication (17.8%); most frequently by the first year students (22.7%).Conclusion: The pattern of self-medication practice changes with time and advancement of knowledge

DESIGN AND CHARACTERIZATION OF DONEPEZIL HYDROCHLORIDE SUSTAINED RELEASE MATRIX TABLETS

The ultimate aim of the present study was to develop sustained release (SR) tablets of Donepezil Hydrochloride by employing natural polymers (Guar gum and Xanthan gum) as the matrix material in different proportion by wet granulation method. Initially drug-excipients compatibility studies were carried out using FTIR and DSC which showed no interaction between drug and excipients. Granules of prepared batches were evaluated for bulk density, tapped density, carr’s index, hausner’s ratio, angle of repose. Tablets were evaluated for various physicochemical parameters like hardness, thickness, friability, weight variation test, drug content and in vitro drug release. All the formulation showed compliance with pharmacopoeial standards. 32 full factorial design was applied in which Guar gum (X1) and Xanthan gum (X2) were taken as independent factor and %CDR at 2hr (Y1) and at 12hr (Y2) were taken as response. In-vitro drug release study revealed that as the amount of polymers increased, % CDR decreased. Contour plots as well as response surface plots were constructed to show the effect of X1 and X2 on %CDR and predicted at the concentration of independent variables X1(40mg) and X2(40mg) for maximized response. The kinetic release treatment showed that korsmeyer peppas equation has shown of  r2 0.9517 which was close to one indicating that the dissolution profile fits in Korsmeyer-Peppas model and the mechanism of drug release from these tablets was by non-fickian diffusion mechanism. The optimized batch was kept for stability study at 40 ± 2oC/ 75 ± 5 % RH for a period of 1 month according to ICH guidelines and found to be stable after 1 month of study. Keywords: Sustained release matrix tablet, Donepezil hydrochloride, Guar gum, Xanthan gum, 32 full factorial design

European mtDNA Variants Are Associated With Differential Responses to Cisplatin, an Anticancer Drug: Implications for Drug Resistance and Side Effects.

Background: Cisplatin, a powerful antitumor agent, causes formation of DNA adducts, and activation of apoptotic pathways. Presently, cisplatin resistance develops in up to 70% of patients but the underlying molecular mechanism(s) are unclear and there are no markers to determine which patients will become resistant. Mitochondria play a significant role not only in energy metabolism but also retrograde signaling (mitochondria to nucleus) that modulates inflammation, complement, and apoptosis pathways. Maternally inherited mitochondrial (mt) DNA can be classified into haplogroups representing different ethnic populations that have diverse susceptibilities to diseases and medications. Methods: Transmitochondrial cybrids, where all cell lines possess identical nuclear genomes but either the H (Southern European) or J (Northern European) mtDNA haplogroups, were treated with cisplatin and analyzed for differential responses related to viability, oxidative stress, and expression levels of genes associated with cancer, cisplatin-induced nephrotoxicity and resistance, apoptosis and signaling pathways. Results: The cisplatin-treated-J cybrids showed greater loss of cell viability along with lower levels of reactive oxygen species and mitochondrial membrane potential compared to cisplatin-treated-H cybrids. After cisplatin treatment, J cybrids showed increased gene expression of BAX, CASP3, and CYP51A, but lower levels of SFRP1 compared to untreated-J cybrids. The cisplatin-treated-H cybrids had elevated expression of CDKN1A/P21, which has a role in cisplatin toxicity, compared to untreated-H cybrids. The cisplatin-treated H had higher transcription levels of ABCC1, DHRS2/HEP27, and EFEMP1 compared to cisplatin-treated-J cybrids. Conclusions: Cybrid cell lines that contain identical nuclei but either H mtDNA mitochondria or J mtDNA mitochondria respond differently to cisplatin treatments suggesting involvement of the retrograde signaling (from mitochondria to nucleus) in the drug-induced cell death. Varying toxicities and transcription levels of the H vs. J cybrids after cisplatin treatment support the hypothesis that mtDNA variants play a role in the expression of genes affecting resistance and side effects of cisplatin

Exogenous glucosamine globally protects chondrocytes from the arthritogenic effects of IL-1β

The effects of exogenous glucosamine on the biology of articular chondrocytes were determined by examining global transcription patterns under normal culture conditions and following challenge with IL-1β. Chondrocytes isolated from the cartilage of rats were cultured in several flasks either alone or in the presence of 20 mM glucosamine. Six hours later, one-half of the cultures of each group were challenged with 10 ng/ml IL-1β. Fourteen hours after this challenge, RNA was extracted from each culture individually and used to probe microarray chips corresponding to the entire rat genome. Glucosamine alone had no observable stimulatory effect on the transcription of primary cartilage matrix genes, such as aggrecan, collagen type II, or genes involved in glycosaminoglycan synthesis; however, glucosamine proved to be a potent, broad-spectrum inhibitor of IL-1β. Of the 2,813 genes whose transcription was altered by IL-1β stimulation (P < 0.0001), glucosamine significantly blocked the response in 2,055 (~73%). Glucosamine fully protected the chondrocytes from IL-1-induced expression of inflammatory cytokines, chemokines, and growth factors as well as proteins involved in prostaglandin E(2 )and nitric oxide synthesis. It also blocked the IL-1-induced expression of matrix-specific proteases such as MMP-3, MMP-9, MMP-10, MMP-12, and ADAMTS-1. The concentrations of IL-1 and glucosamine used in these assays were supraphysiological and were not representative of the arthritic joint following oral consumption of glucosamine. They suggest, however, that the potential benefit of glucosamine in osteoarthritis is not related to cartilage matrix biosynthesis, but is more probably related to its ability to globally inhibit the deleterious effects of IL-1β signaling. These results suggest that glucosamine, if administered effectively, may indeed have anti-arthritic properties, but primarily as an anti-inflammatory agent

pH-Weighted amine chemical exchange saturation transfer echo planar imaging visualizes infiltrating glioblastoma cells

BackgroundGiven the invasive nature of glioblastoma, tumor cells exist beyond the contrast-enhancing (CE) region targeted during treatment. However, areas of non-enhancing (NE) tumors are difficult to visualize and delineate from edematous tissue. Amine chemical exchange saturation transfer echo planar imaging (CEST-EPI) is a pH-sensitive molecular magnetic resonance imaging technique that was evaluated in its ability to identify infiltrating NE tumors and prognosticate survival.MethodsIn this prospective study, CEST-EPI was obtained in 30 patients and areas with elevated CEST contrast ("CEST+" based on the asymmetry in magnetization transfer ratio: MTRasym at 3 ppm) within NE regions were quantitated. Median MTRasym at 3 ppm and volume of CEST + NE regions were correlated with progression-free survival (PFS). In 20 samples from 14 patients, image-guided biopsies of these areas were obtained to correlate MTRasym at 3 ppm to tumor and non-tumor cell burden using immunohistochemistry.ResultsIn 15 newly diagnosed and 15 recurrent glioblastoma, higher median MTRasym at 3ppm within CEST + NE regions (P = .007; P = .0326) and higher volumes of CEST + NE tumor (P = .020; P &lt; .001) were associated with decreased PFS. CE recurrence occurred in areas of preoperative CEST + NE regions in 95.4% of patients. MTRasym at 3 ppm was correlated with presence of tumor, cell density, %Ki-67 positivity, and %CD31 positivity (P = .001; P &lt; .001; P &lt; .001; P = .001).ConclusionspH-weighted amine CEST-EPI allows for visualization of NE tumor, likely through surrounding acidification of the tumor microenvironment. The magnitude and volume of CEST + NE tumor correlates with tumor cell density, degree of proliferating or "active" tumor, and PFS

Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Preterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation. METHODS: ASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks\u27 gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970. FINDINGS: From March 23, 2016 to June 30, 2018, 14 361 women were screened for inclusion and 11 976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks\u27 gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (\u3c34 \u3eweeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups. INTERPRETATION: In populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development