Incidence of HIV-positive admission and inpatient mortality in Malawi (2012-2019).

OBJECTIVE: To investigate trends in population incidence of HIV-positive hospital admission and risk of in-hospital death among adults living with HIV between 2012 and 2019 in Blantyre, Malawi. DESIGN: Population cohort study using an existing electronic health information system ('SPINE') at Queen Elizabeth Central Hospital and Blantyre census data. METHODS: We used multiple imputation and negative binomial regression to estimate population age-specific and sex-specific admission rates over time. We used a log-binomial model to investigate trends in risk of in-hospital death. RESULTS: Of 32 814 adult medical admissions during Q4 2012--Q3 2019, HIV status was recorded for 75.6%. HIV-positive admissions decreased substantially between 2012 and 2019. After imputation for missing data, HIV-positive admissions were highest in Q3 2013 (173 per 100 000 adult Blantyre residents) and lowest in Q3 2019 (53 per 100 000 residents). An estimated 10 818 fewer than expected people with HIV (PWH) [95% confidence interval (CI) 10 068-11 568] were admitted during 2012-2019 compared with the counterfactual situation where admission rates stayed the same throughout this period. Absolute reductions were greatest for women aged 25-34 years (2264 fewer HIV-positive admissions, 95% CI 2002-2526). In-hospital mortality for PWH was 23.5%, with no significant change over time in any age-sex group, and no association with antiretroviral therapy (ART) use at admission. CONCLUSION: Rates of admission for adult PWH decreased substantially, likely because of large increases in community provision of HIV diagnosis, treatment and care. However, HIV-positive in-hospital deaths remain unacceptably high, despite improvements in ART coverage. A concerted research and implementation agenda is urgently needed to reduce inpatient deaths among PWH

LipocalinPred: a SVM-based method for prediction of lipocalins

<p>Abstract</p> <p>Background</p> <p>Functional annotation of rapidly amassing nucleotide and protein sequences presents a challenging task for modern bioinformatics. This is particularly true for protein families sharing extremely low sequence identity, as for lipocalins, a family of proteins with varied functions and great diversity at the sequence level, yet conserved structures.</p> <p>Results</p> <p>In the present study we propose a SVM based method for identification of lipocalin protein sequences. The SVM models were trained with the input features generated using amino acid, dipeptide and secondary structure compositions as well as PSSM profiles. The model derived using both PSSM and secondary structure emerged as the best model in the study. Apart from achieving a high prediction accuracy (>90% in leave-one-out), lipocalinpred correctly differentiates closely related fatty acid-binding proteins and triabins as non-lipocalins.</p> <p>Conclusion</p> <p>The method offers a promising approach as a lipocalin prediction tool, complementing PROSITE, Pfam and homology modelling methods.</p

Therapeutic targeting of Krüppel-like factor 4 abrogates microglial activation

<p>Abstract</p> <p>Background</p> <p>Neuroinflammation occurs as a result of microglial activation in response to invading micro-organisms or other inflammatory stimuli within the central nervous system. According to our earlier findings, Krüppel-like factor 4 (Klf4), a zinc finger transcription factor, is involved in microglial activation and subsequent release of proinflammatory cytokines, tumor necrosis factor alpha, macrophage chemoattractant protein-1 and interleukin-6 as well as proinflammatory enzymes, inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-treated microglial cells. Our current study focuses on finding the molecular mechanism of the anti-inflammatory activities of honokiol in lipopolysaccharide-treated microglia with emphasis on the regulation of Klf4.</p> <p>Methods</p> <p>For <it>in vitro </it>studies, mouse microglial BV-2 cell lines as well as primary microglia were treated with 500 ng/mL lipopolysaccharide as well as 1 μM and 10 μM of honokiol. We cloned full-length Klf4 cDNA in pcDNA3.1 expression vector and transfected BV-2 cells with this construct using lipofectamine for overexpression studies. For <it>in vivo </it>studies, brain tissues were isolated from BALB/c mice treated with 5 mg/kg body weight of lipopolysaccharide either with or without 2.5 or 5 mg/kg body weight of honokiol. Expression of Klf4, cyclooxygenase-2, inducible nitric oxide synthase and phospho-nuclear factor-kappa B was measured using immunoblotting. We also measured the levels of cytokines, reactive oxygen species and nitric oxide in different conditions.</p> <p>Results</p> <p>Our findings suggest that honokiol can substantially downregulate the production of proinflammatory cytokines and inflammatory enzymes in lipopolysaccharide-stimulated microglia. In addition, honokiol downregulates lipopolysaccharide-induced upregulation of both Klf4 and phospho-nuclear factor-kappa B in these cells. We also found that overexpression of Klf4 in BV-2 cells suppresses the anti-inflammatory action of honokiol.</p> <p>Conclusions</p> <p>Honokiol potentially reduces inflammation in activated microglia in a Klf4-dependent manner.</p

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Arousal of Cancer-Associated Stroma: Overexpression of Palladin Activates Fibroblasts to Promote Tumor Invasion

Background: Cancer-associated fibroblasts, comprised of activated fibroblasts or myofibroblasts, are found in the stroma surrounding solid tumors. These myofibroblasts promote invasion and metastasis of cancer cells. Mechanisms regulating the activation of the fibroblasts and the initiation of invasive tumorigenesis are of great interest. Upregulation of the cytoskeletal protein, palladin, has been detected in the stromal myofibroblasts surrounding many solid cancers and in expression screens for genes involved in invasion. Using a pancreatic cancer model, we investigated the functional consequence of overexpression of exogenous palladin in normal fibroblasts in vitro and its effect on the early stages of tumor invasion. Principal Findings: Palladin expression in stromal fibroblasts occurs very early in tumorigenesis. In vivo, concordant expression of palladin and the myofibroblast marker, alpha smooth muscle actin (a-SMA), occurs early at the dysplastic stages in peri-tumoral stroma and progressively increases in pancreatic tumorigenesis. In vitro introduction of exogenous 90 kD palladin into normal human dermal fibroblasts (HDFs) induces activation of stromal fibroblasts into myofibroblasts as marked by induction of a-SMA and vimentin, and through the physical change of cell morphology. Moreover, palladin expression in the fibroblasts enhances cellular migration, invasion through the extracellular matrix, and creation of tunnels through which cancer cells can follow. The fibroblast invasion and creation of tunnels results from the development o