Prediction of patient survival from heart failure using a cox-based model

The existing heart failure risk prediction models are developed based on machine learning predictors. The objective of this study is to identify the key risk factors that affect the survival time of heart patients and to develop a heart failure survival prediction model using the identified risk factors. A cox proportional hazard regression method is applied to generate the proposed heart failure survival model. We used the dataset from the University of California Irvine (UCI) clinical heart failure data repository. To develop the model we have used multiple risk factors such as age, anemia, creatinine phosphokinase, diabetes history, ejection fraction, presence of high blood pressure, platelet count, serum creatinine, sex, and smoking history. Among the risk factors, high blood pressure is identified as one of the novel risk factors for heart failure. We have validated the performance of the model via statistical and empirical validation. The experimental result shows that the proposed model achieved good discrimination and calibration ability with a C-index (receiver operating characteristic (ROC) of being 0.74 and a log-likelihood ratio of 81.95 using 11 degrees of freedom on the validation dataset

Protein kinase A (PknA) of Mycobacterium tuberculosis is independently activated and is critical for growth in vitro and survival of the pathogen in the host

The essential mycobacterial protein kinases PknA and PknB play crucial roles in modulating cell shape and division. However, the precise in vivo functional aspects of PknA have not been investigated. This study aims to dissect the role of PknA in mediating cell survival in vitro as well as in vivo. We observed aberrant cell shape and severe growth defects when PknA was depleted. Using the mouse infection model, we observe that PknA is essential for survival of the pathogen in the host. Complementation studies affirm the importance of the kinase, juxtamembrane and transmembrane domains of PknA. Surprisingly, the extracytoplasmic domain is dispensable for cell growth and survival in vitro. We find that phosphorylation of the activation loop at Thr172 of PknA is critical for bacterial growth. PknB has been previously suggested to be the receptor kinase, which activates multiple kinases, including PknA, by trans-phosphorylating their activation loop residues. Using phospho-specific PknA antibodies and conditional pknB mutant, we find that PknA autophosphorylates its activation loop independent of PknB. Fluorescently tagged PknA and PknB show distinctive distribution patterns within the cell, suggesting that although both kinases are known to modulate cell shape and division, their modes of action are likely to be different. This is supported by our findings that expression of kinase-dead PknA versus kinase-dead PknB in mycobacterial cells leads to different cellular phenotypes. Data indicate that although PknA and PknB are expressed as part of the same operon, they appear to be regulating cellular processes through divergent signaling pathways

Insights of carbon footprint of tea through life cycle approach

Stabilizing GHG emissions in the agri-food sector is crucial for climate change mitigation. Tea is one of the most consumed drinks worldwide and such high levels of consumption necessitate for the carbon footprint (CF) assessment of its entire life cycle encompassing all six stages such as cultivation, processing, packaging, transportation, consumption and disposal to understand the environmental impact of tea industry at large. In this context, this study is a maiden attempt to quantify and compare CF for the entire life cycle of all three types of tea such as black, green and white tea in a single research paper by employing the life cycle assessment (LCA) method in significant tea growing areas of Tamil Nadu, India. The findings revealed that the consumption stage contributed the highest CO2 emissions, accounting for 45%-56% to overall CF. Black tea consumption contributed 45% (5.8 kg CO2-eq/kg of made tea) of the total CF, while green tea and white tea had higher CF (8.3 kg CO?-eq/kg of made tea), contributing 56% to the total CF. The processing stage was the second largest source, contributing 12-19% to overall CF, followed by packaging (15-17%) and cultivation (10-11%) stages. Overall, the total CF (cradle to grave) for black tea and white tea had a similar value of 12.9 kg CO2-eq/kg of made tea, whereas green tea registered a higher value of 14.79 kg CO2-eq/kg of made tea. Furthermore, this assessment identified hotspots of GHG emissions. It enabled the recommendation of CF reduction measures to promote carbon neutrality in tea sector while being a part of global climate change mitigation efforts

Portable microfluidic chip for detection of Escherichia coli in produce and blood

Pathogenic agents can lead to severe clinical outcomes such as food poisoning, infection of open wounds, particularly in burn injuries and sepsis. Rapid detection of these pathogens can monitor these infections in a timely manner improving clinical outcomes. Conventional bacterial detection methods, such as agar plate culture or polymerase chain reaction, are time-consuming and dependent on complex and expensive instruments, which are not suitable for point-of-care (POC) settings. Therefore, there is an unmet need to develop a simple, rapid method for detection of pathogens such as Escherichia coli. Here, we present an immunobased microchip technology that can rapidly detect and quantify bacterial presence in various sources including physiologically relevant buffer solution (phosphate buffered saline [PBS]), blood, milk, and spinach. The microchip showed reliable capture of E. coli in PBS with an efficiency of 71.8% ± 5% at concentrations ranging from 50 to 4,000 CFUs/mL via lipopolysaccharide binding protein. The limits of detection of the microchip for PBS, blood, milk, and spinach samples were 50, 50, 50, and 500 CFUs/mL, respectively. The presented technology can be broadly applied to other pathogens at the POC, enabling various applications including surveillance of food supply and monitoring of bacteriology in patients with burn wounds

Novel synthesis of carbon dots from coconut wastes and its potential as water disinfectant

This paper presents a facile and effective method for the large-scale production of carbon dots (CDs) from diverse coconut wastes (fronds, husk and shell). On comparing two different methods, namely (i) hydrothermal carbonization and (ii) novel sequential synthesis processes (pyrolysis followed by sonication), the latter procedure recorded a higher recovery of CDs (14.0%) over the hydrothermal method (2.33%). Doping agents such as urea, polyethyleneimine (PEI) and hexamethylenetetramine (HMTA) were chosen at varying concentrations to synthesize surface-modified CDs (SMCDs) for enhanced antibacterial properties. Among these SMCDs, urea-doped CDs (1:1) @ 1000 ppm registered significantly higher cytotoxicity (20.6%) against Escherichia coli (E. coli). Subsequently, to assess the applicability of CDs as a disinfectant in water purification systems, two products, namely (i) CD-infused chitosan beads and (ii) pelletized CDs, were developed to ensure the immobilization of CDs. Studies with lab-scale prototypes have revealed that CDs infused chitosan beads reduced the colonies of E. coli from 5.41 × 102 CFU/mL (control group) to 2.16 × 102 CFU/mL, in comparison with pelletized CDs that decreased to 3.30 × 102 CFU/mL. The biosafety of CDs was assessed against Eisenia fetida for 21 days, and the observations revealed no mortality, even at 2000 ppm. Overall, this research demonstrated that a waste biomass can be effectively transformed into a novel water disinfectant. Furthermore, this scientific endeavor opens up research avenues to evolve advanced water purifiers using low-cost and eco-friendly nanomaterials

Provide Proactive Reproducible Analysis Transparency with Every Publication

The high incidence of irreproducible research has led to urgent appeals for transparency and equitable practices in open science. For the scientific disciplines that rely on computationally intensive analyses of large data sets, a granular understanding of the analysis methodology is an essential component of reproducibility. This paper discusses the guiding principles of a computational reproducibility framework that enables a scientist to proactively generate a complete reproducible trace as analysis unfolds, and share data, methods and executable tools as part of a scientific publication, allowing other researchers to verify results and easily re-execute the steps of the scientific investigation

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Speckle Tracking Echocardiography Detects Strain Changes in Murine Heart during Acute Ischemia Perfusion

Myocardial infarction (MI) is the leading cause of mortality and morbidity worldwide. Rapid loss of cardiomyocytes induced by MI and subsequent reperfusion results in remodeling of left ventricular (LV) cardiac architecture to support the contractile functioning of the heart. The functioning of such a remodeled heart subsequently leads to a heart failure. Though global strain measurements are considered to be an index to characterize heart function, the prognosis of an imminent heart failure needs better understanding for providing adequate treatment. This is because, vital measurement parameters such as the ejection fraction (EF), LV end-systolic stroke volume remains within normal limits and hence, measurement of LV global function remains insufficient. 2D-Speckle tracking echocardiography (STE) is a novel method for determining both globular and regional strain and strain rate. The principle used in STE is the measurement of distance between 2 stable patterns or “speckles” on a 2D echocardiographic image of a LV segment during a cardiac cycle.The aims of our study were to measure regional myocardial strain and strain rate in both the radial (Sr) and longitudinal (Sl) (MI) and (MI+MSC) hearts using STE to detect changes in LV wall deformation within hours after MI. MI was performed by ligation of the left coronary artery for 90 minutes followed by reperfusion for 24 hours. The mean strain values for the radial strain at the post.apex were measured at MI (5.65±1.36 %), MI+MSC (17.87±2.93 %), and at the Ant apex it was measured at MI (6.69±1.36%) and MI+MSC (15.56±2.92%). The longitudinal strain for the post apex at MI (-8.40±3.44 %) MI+MSC (-11.65±2.33 %) & ant apex at MI (-4.79±0.57 1/s) and MI+MSC (-5.67±1.29 1/s). Overall, our data demonstrated an increase in strain and strain rate measures with the introduction of stem cells when compared to a sham & a MI group with no stem cells. The presence of stem cells altered the strain and strain rate values in a positive manner

Yielding behaviour of cemented binary mixture

Cement stabilization is commonly used for improving soft soils and the mechanical behaviour of cemented pure clay has been well documented. However, limited studies have investigated the effect of sand in a cement-clay matrix because the conventional water to solid (solid includes soil and cement) ratio cannot be simply used to characterize the behaviour of cemented binary mixture. The water holding capacity of the mixture reduces with increase in sand content, when the water to solid ratio is kept constant. In this study, the ratio of water to clay and cement is kept constant, so that the effect of sand content could be studied. The materials used in this study are kaolin clay, sand with D50 of 0.71 mm and Ordinary Portland cement type 1. Sand content varies from 0% to 50% and curing time is kept constant at 7 days. We used three ratios of water to clay and cement which correspond to 139%, 104% and 78%. The isotropic yield point increases with increase in sand content and cement content, while it reduces with increase in water content. A power function captures the variation of yield point with the ratio of water to cement and clay