Analysis of an inflection s-shaped software reliability model considering log-logistic testing-effort and imperfect debugging

Gokhale and Trivedi (1998) have proposed the Log-logistic software reliability growth model that can capture the increasing/decreasing nature of the failure occurrence rate per fault. In this paper, we will first show that a Log-logistic testing-effort function (TEF) can be expressed as a software development/testing-effort expenditure curve. We investigate how to incorporate the Log-logistic TEF into inflection S-shaped software reliability growth models based on non-homogeneous Poisson process (NHPP). The models parameters are estimated by least square estimation (LSE) and maximum likelihood estimation (MLE) methods. The methods of data analysis and comparison criteria are presented. The experimental results from actual data applications show good fit. A comparative analysis to evaluate the effectiveness for the proposed model and other existing models are also performed. Results show that the proposed models can give fairly better predictions. Therefore, the Log-logistic TEF is suitable for incorporating into inflection S-shaped NHPP growth models. In addition, the proposed models are discussed under imperfect debugging environment

Co-activation of Gi and Gq proteins exerts synergistic effect on human platelet aggregation through activation of phospholipase C and Ca2+ signalling pathways

Our previous studies have shown that subthreshold concentrations of two platelet agonists exert synergistic effects on platelet aggregation. Here we studied the mechanism of synergistic interaction of 5-hydroxytryptamine (5-HT) and epinephrine mediated platelet aggregation. We show that 5-HT had no or little effect on aggregation but it did potentiate the aggregation response of epinephrine. The synergistic interaction of 5-HT (1-5 microM) and epinephrine (0.5-2 microM) was inhibited by alpha2-adrenoceptor blocker (yohimbine; IC50= 0.4 microM), calcium channel blockers (verapamil and diltiazem with IC50 of 10 and 48 mM, respectively), PLC inhibitor (U73122; IC50=6 microM) and nitric oxide (NO) donor, SNAP (IC50=1.6 microM)). The data suggest that synergistic effects of platelet agonists are receptor-mediated and occur through multiple signalling pathways including the activation PLC/Ca2+ signalling cascades

Cost of Severe Chronic Obstructive Pulmonary Disease Exacerbations in a High Burden Region in North India

Background: Data on costs of acute exacerbations of COPD (AECOPD) in low-income countries are sparse. We conducted a prospective survey to assess direct and indirect costs of severe AECOPD in a tertiary care setting in a high prevalence area of North India. Methods: We conducted face-to-face surveys using a semi-structured questionnaire among a convenience sample of 129 consenting patients admitted with AECOPD. Data were collected on out-of-pocket costs of hospitalization, consultation, medications, diagnostics, transportation, lodging, and missed work days for self and their attendants. Out-of-pocket costs were supplemented with World Health Organization-CHOICE estimates. Missed work-days were valued on per capita national income (Indian Rupees [INR] 68,748, US$1,145.8). Median total cost per exacerbation episode was INR 44,390 (Inter-quartile range [IQR]: INR 33,354–63,642; US$739.8, IQR: 555.9–1060.7). Hospital costs constituted the largest component of the costs (71%) followed by other costs directly borne by the patient himself (29%), medicine costs (14%), transportation charges (2%) and diagnostic tests (3%). Indirect costs to caregivers (median INR 1,544, IQR: INR 0–17,370 INR; US$25.7, IQR: US$0–289.5), calculated as financial loss due to missed work days, accounted for 4% of the total cost. Expenses were covered by family members in all but 11 patients. Conclusions: AECOPD in India are associated with substantial costs and strategies to reduce the burden of disease such as smoking cessation, influenza and pneumococcal vaccination, etc should be aggressively pursued

Antimicrobial, anticancer, and biofilm inhibition studies of highly reduced graphene oxide (HRG): In vitro and in silico analysis

Background: Bacterial infections and cancers may cause various acute or chronic diseases, which have become serious global health issues. This requires suitable alternatives involving novel and efficient materials to replace ineffective existing therapies. In this regard, graphene composites are being continuously explored for a variety of purposes, including biomedical applications, due to their remarkable properties.Methods: Herein, we explore, in-vitro, the different biological properties of highly reduced graphene oxide (HRG), including anti-cancer, anti-bacterial, and anti-biofilm properties. Furthermore, to analyze the interactions of graphene with proteins of microbes, in silico docking analysis was also carried out. To do this, HRG was prepared using graphene oxide as a precursor, which was further chemically reduced to obtain the final product. The as-prepared HRG was characterized using different types of microscopic and spectroscopic techniques.Results: The HRG revealed significant cytotoxic ability, using a dose-dependent anti-cell proliferation approach, which substantially killed human breast cancer cells (MCF-7) with IC50 of 29.51 ± 2.68 μg/mL. The HRG demonstrated efficient biological properties, i.e., even at low concentrations, HRG exhibited efficient anti-microbial properties against a variety of microorganisms. Among the different strains, Gram-positive bacteria, such as B. subtilis, MRSA, and S. aureus are more sensitive to HRG compared to Gram-negative bacteria. The bactericidal properties of HRG are almost similar to a commercially available effective antibiotic (ampicillin). To evaluate the efficacy of HRG against bacterial biofilms, Pseudomonas aeruginosa and MRSA were applied, and the results were compared with gentamycin and ampicillin, which are commonly applied standard antibiotics. Notably, HRG demonstrated high inhibition (94.23%) against P.aeruginosa, with lower MIC (50 μg/mL) and IC50 (26.53 μg/mL) values, whereas ampicillin and gentamicin showed similar inhibition (90.45% and 91.31% respectively) but much higher MIC and IC50 values.Conclusion: Therefore, these results reveal the excellent biopotential of HRG in different biomedical applications, including cancer therapy; antimicrobial activity, especially anti-biofilm activity; and other biomedicine-based therapies. Based on the molecular docking results of Binding energy, it is predicted that pelB protein and HRG would form the best stable docking complex, and high hydrogen and hydrophobic interactions between the pelB protein and HRG have been revealed. Therefore, we conclude that HRG could be used as an antibiofilm agent against P. aeruginosa infections

Bone Marrow Stromal Cell Transplantation Mitigates Radiation-Induced Gastrointestinal Syndrome in Mice

Nuclear accidents and terrorism presents a serious threat for mass casualty. While bone-marrow transplantation might mitigate hematopoietic syndrome, currently there are no approved medical countermeasures to alleviate radiation-induced gastrointestinal syndrome (RIGS), resulting from direct cytocidal effects on intestinal stem cells (ISC) and crypt stromal cells. We examined whether bone marrow-derived adherent stromal cell transplantation (BMSCT) could restitute irradiated intestinal stem cells niche and mitigate radiation-induced gastrointestinal syndrome.Autologous bone marrow was cultured in mesenchymal basal medium and adherent cells were harvested for transplantation to C57Bl6 mice, 24 and 72 hours after lethal whole body irradiation (10.4 Gy) or abdominal irradiation (16-20 Gy) in a single fraction. Mesenchymal, endothelial and myeloid population were characterized by flow cytometry. Intestinal crypt regeneration and absorptive function was assessed by histopathology and xylose absorption assay, respectively. In contrast to 100% mortality in irradiated controls, BMSCT mitigated RIGS and rescued mice from radiation lethality after 18 Gy of abdominal irradiation or 10.4 Gy whole body irradiation with 100% survival (p<0.0007 and p<0.0009 respectively) beyond 25 days. Transplantation of enriched myeloid and non-myeloid fractions failed to improve survival. BMASCT induced ISC regeneration, restitution of the ISC niche and xylose absorption. Serum levels of intestinal radioprotective factors, such as, R-Spondin1, KGF, PDGF and FGF2, and anti-inflammatory cytokines were elevated, while inflammatory cytokines were down regulated.Mitigation of lethal intestinal injury, following high doses of irradiation, can be achieved by intravenous transplantation of marrow-derived stromal cells, including mesenchymal, endothelial and macrophage cell population. BMASCT increases blood levels of intestinal growth factors and induces regeneration of the irradiated host ISC niche, thus providing a platform to discover potential radiation mitigators and protectors for acute radiation syndromes and chemo-radiation therapy of abdominal malignancies

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe