Study of Ventilator Associated Pneumonia in Neonatal Intensive Care Unit: characteristics, risk factors and outcome

Ventilator Associated Pneumonia (VAP), the nosocomial pneumonia developing in mechanically ventilated patients after 48 hours of mechanical ventilation, is the second most common nosocomial infection.Therefore, there is a vital need to study the etiology and risk factors associated with VAP in neonates. Neonates admitted to neonatal intensive care unit (NICU), over a period of 1 year and who required mechanical ventilation for more than 48 hours were enrolled consecutively into the study. Diagnosis of VAP was made by the guidelines given by National Nosocomial infection Surveillance System (NNIS, 1996). Semi-quantitative assay of endotracheal aspirate was used for microbiological diagnoses of VAP. 105CFU/ml was taken as the cut off between evidence of pathological infection and colonization. The risk factors such as birth weight, prematurity (gestational age < 37 weeks), duration of mechanical ventilation, number of reintubations, length of hospital stay, primary diagnosis of neonate, postnatal age and small for gestational age (SGA) were studied for the development of VAP. Risk factors found significant on bivariate analysis were subjected to multiple regression analysis to determine the most important predictors of VAP. The study group comprised of 98 neonates out of which, 30 neonates developed VAP (30.6%). VAP rates were 37.2 per 1000 days of mechanical ventilation. Most common bacterial isolated from endotracheal aspirate of VAP patients was Klebsiella spp (32.8%), E.coli (23.2%) and Acinetobacter (17.8%) being the other two common organisms. Very low birth weight

Ensemble Sales Forecasting Study in Semiconductor Industry

Sales forecasting plays a prominent role in business planning and business strategy. The value and importance of advance information is a cornerstone of planning activity, and a well-set forecast goal can guide sale-force more efficiently. In this paper CPU sales forecasting of Intel Corporation, a multinational semiconductor industry, was considered. Past sale, future booking, exchange rates, Gross domestic product (GDP) forecasting, seasonality and other indicators were innovatively incorporated into the quantitative modeling. Benefit from the recent advances in computation power and software development, millions of models built upon multiple regressions, time series analysis, random forest and boosting tree were executed in parallel. The models with smaller validation errors were selected to form the ensemble model. To better capture the distinct characteristics, forecasting models were implemented at lead time and lines of business level. The moving windows validation process automatically selected the models which closely represent current market condition. The weekly cadence forecasting schema allowed the model to response effectively to market fluctuation. Generic variable importance analysis was also developed to increase the model interpretability. Rather than assuming fixed distribution, this non-parametric permutation variable importance analysis provided a general framework across methods to evaluate the variable importance. This variable importance framework can further extend to classification problem by modifying the mean absolute percentage error(MAPE) into misclassify error. Please find the demo code at : https://github.com/qx0731/ensemble_forecast_methodsComment: 14 pages, Industrial Conference on Data Mining 2017 (ICDM 2017

Comparative evaluation of egg based solid media for primary isolation of Paratuberculosis bacilli

81-87Paratuberculosis caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a prevalent infection and is highly expensive to livestock industry. Paratuberculosis also has zoonotic concerns with Crohn&rsquo;s disease. Isolation of MAP from infected individuals/samples is the most vital for downstream studies. However, MAP is extremely fastidious organism and primary isolation is extremely difficult. Mycobacterial growth indicator tube (MGIT) medium is most recommended for primary isolation, but this medium is highly expensive and requires sophisticated instrument and is unaffordable for developing and underdeveloped world. Present study aimed to investigate the comparative performance of three different egg based solid media (MB7H10, LJ and HEYM) for the primary isolation of MAP from clinically suspected animals. Animals having signs of paratuberculosis were sampled either from farms in Jaipur District of Western India or slaughterhouse. Slaughtered animals were sampled having swollen &amp; enlarged mesenteric lymph nodes (MLN) with thickened/ corrugated intestine near ileo-cecal junction (ICJ). Fecal samples were collected from suspected cattle, buffalo, goat and sheep. MB7H10 medium showed maximum recovery of MAP isolates from clinical samples. Most of the isolates grew on MB7H10 (41.9 %) followed by LJ (22.3%) and HEYM (6.25 %). In case single medium is to be used MB7H10 is the first choice and combination of MB7H10+LJ is better. In conclusion, combination of MB7H10+LJ is the best choice for solid media for the isolation of the MAP in laboratories

Analytical Method Development and Validation for the Simultaneous Estimation of Aspirin, Clopidogrel and Rosuvastatin in Pharmaceutical Dosage Form

A new, simple, novel, accurate, precise, reliable, rapid and linear reverse phase high-performance liquid chromatography (RP-HPLC) method was developed and fully validated for simultaneous qualitative and quantitative estimation of&nbsp;&nbsp; Rosuvastatin (ROS), Clopidogrel (CLOP) and Aspirin (ASP) in bulk and pharmaceutical dosage form as per International Conference on Harmonization (ICH) guidelines. In the present work, good chromatographic separation was achieved by isocratic method using a Hypersil BDS C18 column (250 mm ×4.6, 5 μm) and a mobile phase consisting of KH2Po4 buffer pH-6.0: acetonitrile in the ratio 60:40, at a flow rate of 1 ml/min. The effluents obtained were monitored at 242nm with the UV-visible detector. The calibration curves obtained were linear (r2=0.999) over the concentration range of 7.5-22.5μg/ml and 1-3μg/ml for CLOP, ASP and ROS respectively. A run time of 7.0 minutes for each sample made it possible to analyze more than 200 samples per day. The retention time of ASP, CLOP and ROS was found to be 3.103 min, 4,277 min and 5.707 min respectively. The high recovery values (99%-101%) indicate a satisfactory accuracy. The low percent relative standard deviation (% RSD) values in the precision study reveal that the method is precise&nbsp; therefore the method can be used for routine monitoring of CLOP, ASP and ROS in industry in the assay of bulk drug and dosage form. Keywords: RP-HPLC, Rosuvastatin, Clopidogrel, Aspirin, Method validation, ICH guidelines

Comparative evaluation of egg based solid media for primary isolation of Paratuberculosis bacilli

Paratuberculosis caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a prevalent infection and is highly expensive to livestock industry. Paratuberculosis also has zoonotic concerns with Crohn’s disease. Isolation of MAP from infected individuals/samples is the most vital for downstream studies. However, MAP is extremely fastidious organism and primary isolation is extremely difficult. Mycobacterial growth indicator tube (MGIT) medium is most recommended for primary isolation, but this medium is highly expensive and requires sophisticated instrument and is unaffordable for developing and underdeveloped world. Present study aimed to investigate the comparative performance of three different egg based solid media (MB7H10, LJ and HEYM) for the primary isolation of MAP from clinically suspected animals. Animals having signs of paratuberculosis were sampled either from farms in Jaipur District of Western India or slaughterhouse. Slaughtered animals were sampled having swollen &amp; enlarged mesenteric lymph nodes (MLN) with thickened/ corrugated intestine near ileo-cecal junction (ICJ). Fecal samples were collected from suspected cattle, buffalo, goat and sheep. MB7H10 medium showed maximum recovery of MAP isolates from clinical samples. Most of the isolates grew on MB7H10 (41.9 %) followed by LJ (22.3%) and HEYM (6.25 %). In case single medium is to be used MB7H10 is the first choice and combination of MB7H10+LJ is better. In conclusion, combination of MB7H10+LJ is the best choice for solid media for the isolation of the MAP in laboratories

Linear ubiquitin chain assembly complex coordinates late thymic T-cell differentiation and regulatory T-cell homeostasis.

The linear ubiquitin chain assembly complex (LUBAC) is essential for innate immunity in mice and humans, yet its role in adaptive immunity is unclear. Here we show that the LUBAC components HOIP, HOIL-1 and SHARPIN have essential roles in late thymocyte differentiation, FOXP3(+) regulatory T (Treg)-cell development and Treg cell homeostasis. LUBAC activity is not required to prevent TNF-induced apoptosis or necroptosis but is necessary for the transcriptional programme of the penultimate stage of thymocyte differentiation. Treg cell-specific ablation of HOIP causes severe Treg cell deficiency and lethal immune pathology, revealing an ongoing requirement of LUBAC activity for Treg cell homeostasis. These data reveal stage-specific requirements for LUBAC in coordinating the signals required for T-cell differentiation

Lipopolysaccharide modifies amiloride-sensitive Na+ transport processes across human airway cells: role of mitogen-activated protein kinases ERK 1/2 and 5

Bacterial lipopolysaccharides (LPS) are potent inducers of proinflammatory signaling pathways via the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK), causing changes in the processes that control lung fluid homeostasis and contributing to the pathogenesis of lung disease. In human H441 airway epithelial cells, incubation of cells with 15 µg ml−1 LPS caused a significant reduction in amiloride-sensitive Isc from 15 ± 2 to 8 ± 2 µA cm−2 (p = 0.01, n = 13) and a shift in IC50 amiloride of currents from 6.8 × 10−7 to 6.4 × 10−6 M. This effect was associated with a decrease in the activity of 5 pS, highly Na+ selective, amiloride-sensitive <1 µM channels (HSC) and an increase in the activity of ∼18 pS, nonselective, amiloride-sensitive >10 µM cation channels (NSC) in the apical membrane. LPS decreased αENaC mRNA and protein abundance, inferring that LPS inhibited αENaC gene expression. This correlated with the decrease in HSC activity, indicating that these channels, but not NSCs, were comprised of at least αENaC protein. LPS increased NF-κB DNA binding activity and phosphorylation of extracellular signal-related kinase (ERK)1/2, but decreased phosphorylation of ERK5 in H441 cells. Pretreatment of monolayers with PD98059 (20 µM) inhibited ERK1/2 phosphorylation, promoted phosphorylation of ERK5, increased αENaC protein abundance, and reversed the effect of LPS on Isc and the shift in amiloride sensitivity. Inhibitors of NF-κB activation were without effect. Taken together, our data indicate that LPS acts via ERK signaling pathways to decrease αENaC transcription, reducing HSC/ENaC channel abundance, activity, and transepithelial Na+ transport in H441 airway epithelial cells

Vesicle miR-195 derived from endothelial cells inhibits expression of serotonin transporter in vessel smooth muscle cells

Serotonin or 5-hydroxytryptamine (5-HT) has been shown to be essential in lots of physiological and pathological processes. It is well known that 5-HT and 5-HT transporter (5-HTT) play important roles in the pulmonary artery in pulmonary hypertension. However, little is known about the function of 5-HTT in other arteries. In this study we found that the expression of 5-HTT was elevated in injured carotid arteries and over-expression of 5-HTT induced proliferation of smooth muscle cells (SMCs); however, this phenotype could be reversed by knocking-down of 5-HTT or endothelial cells conditional medium (EC-CM). A 5-HTT inhibitor, fluoxetine, treated animals also exhibited reduced restenosis after injury. We identified that miR-195 was packaged in the extracellular vesicles from EC-CM. We further confirmed that extracellular vesicles could transfer miR-195 from ECs to SMCs to inhibit the expression of 5-HTT in SMCs and the proliferation of SMCs. These results provide the first evidence that ECs communicate with SMCs via micro-RNA195 in the regulation of the proliferation of SMCs through 5-HTT, which will contribute to a better understanding of communications between ECs and SMCs via micro-RNA. Our findings suggest a potential target for the control of vessel restenosis

When to Start Antiretroviral Therapy

The question of when to start combination antiretroviral therapy for treatment-naïve patients has always been controversial. This is particularly true in the current era, with major guidelines recommending very different treatment strategies. Despite a lack of clarity regarding the optimal time to begin therapy, there has been a recent shift toward earlier initiation. This more aggressive approach is driven by several observations. First, effective viral suppression with therapy can prevent non-AIDS-related morbidity and mortality. Second, therapy can prevent irreversible harm to the human immune system. Third, therapy may prevent transmission of HIV to others, and thus have a potential public health benefit. For patients who are motivated and willing to initiate early treatment, the collective benefits of early therapy may outweigh the well-documented risks of antiretroviral medications