The diagnosis of dengue in patients presenting with acute febrile illness using supervised machine learning and impact of seasonality

Background: Symptomatic dengue infection can result in a life-threatening shock syndrome and timely diagnosis is essential. Point-of-care tests for non-structural protein 1 and IgM are used widely but performance can be limited. We developed a supervised machine learning model to predict whether patients with acute febrile illnesses had a diagnosis of dengue or other febrile illnesses (OFI). The impact of seasonality on model performance over time was examined. Methods: We analysed data from a prospective observational clinical study in Vietnam. Enrolled patients presented with an acute febrile illness of 90%). Conclusion: Supervised machine learning models are able to discriminate between dengue and OFI diagnoses in patients presenting with an early undifferentiated febrile illness. These models could be of clinical utility in supporting healthcare decision-making and provide passive surveillance across dengue endemic regions. Effects of seasonality and changing disease prevalence must however be taken into account—this is of significant importance given unpredictable effects of human-induced climate change and the impact on health

Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma

There is currently no standard salvage chemotherapy regimen in relapsed and refractory lymphoma. Gemcitabine is a novel nucleoside analogue, which acts synergistically with cisplatin both in vitro and in clinical studies. We evaluated the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) in 41 heavily pretreated patients with relapsed and refractory Hodgkin's and non-Hodgkin's lymphoma. The best-achieved response rate (RR) was 79% (95% CI 64–91), with a complete RR of 21%. In patients with chemo-resistant disease, the RR was 63%. Myelosuppression was the main toxicity, the incidence of Grade 3 or 4 anaemia, neutropenia and thrombocytopenia was 17.1, 61.0 and 53.7% respectively. Only one patient had neutropenic sepsis and none of the patients suffered from haemorrhage. Grade 3 or 4 nonhaematological toxicity was minimal and stem cell mobilisation was not inhibited. GEM-P is an effective salvage regimen and its use prior to autologous stem cell transplant warrants further investigation

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Dengue Virus Activates Polyreactive, Natural IgG B Cells after Primary and Secondary Infection

BACKGROUND: Dengue virus is transmitted by mosquitoes and has four serotypes. Cross-protection to other serotypes lasting for a few months is observed following infection with one serotype. There is evidence that low-affinity T and/or B cells from primary infections contribute to the severe syndromes often associated with secondary dengue infections. such pronounced immune-mediated enhancement suggests a dengue-specific pattern of immune cell activation. This study investigates the acute and early convalescent B cell response leading to the generation of cross-reactive and neutralizing antibodies following dengue infection. METHODOLOGY/PRINCIPAL FINDINGS: We assayed blood samples taken from dengue patients with primary or secondary infection during acute disease and convalescence and compared them to samples from patients presenting with non-dengue related fever. Dengue induced massive early plasmablast formation, which correlated with the appearance of polyclonal, cross-reactive IgG for both primary and secondary infection. Surprisingly, the contribution of IgG to the neutralizing titer 4-7 days after fever onset was more than 50% even after primary infection. CONCLUSIONS/SIGNIFICANCE: Poly-reactive and virus serotype cross-reactive IgG are an important component of the innate response in humans during both primary and secondary dengue infection, and "innate specificities" seem to constitute part of the adaptive response in dengue. While of potential importance for protection during secondary infection, cross-reactive B cells will also compete with highly neutralizing B cells and possibly interfere with their development

Niclosamide Prevents the Formation of Large Ubiquitin-Containing Aggregates Caused by Proteasome Inhibition

Protein aggregation is a hallmark of many neurodegenerative diseases and has been linked to the failure to degrade misfolded and damaged proteins. In the cell, aberrant proteins are degraded by the ubiquitin proteasome system that mainly targets short-lived proteins, or by the lysosomes that mostly clear long-lived and poorly soluble proteins. Both systems are interconnected and, in some instances, autophagy can redirect proteasome substrates to the lysosomes.To better understand the interplay between these two systems, we established a neuroblastoma cell population stably expressing the GFP-ubiquitin fusion protein. We show that inhibition of the proteasome leads to the formation of large ubiquitin-containing inclusions accompanied by lower solubility of the ubiquitin conjugates. Strikingly, the formation of the ubiquitin-containing aggregates does not require ectopic expression of disease-specific proteins. Moreover, formation of these focused inclusions caused by proteasome inhibition requires the lysine 63 (K63) of ubiquitin. We then assessed selected compounds that stimulate autophagy and found that the antihelmintic chemical niclosamide prevents large aggregate formation induced by proteasome inhibition, while the prototypical mTORC1 inhibitor rapamycin had no apparent effect. Niclosamide also precludes the accumulation of poly-ubiquitinated proteins and of p62 upon proteasome inhibition. Moreover, niclosamide induces a change in lysosome distribution in the cell that, in the absence of proteasome activity, may favor the uptake into lysosomes of ubiquitinated proteins before they form large aggregates.Our results indicate that proteasome inhibition provokes the formation of large ubiquitin containing aggregates in tissue culture cells, even in the absence of disease specific proteins. Furthermore our study suggests that the autophagy-inducing compound niclosamide may promote the selective clearance of ubiquitinated proteins in the absence of proteasome activity

Healthcare professionals' intentions and behaviours: A systematic review of studies based on social cognitive theories

<p>Abstract</p> <p>Background</p> <p>There is an important gap between the implications of clinical research evidence and the routine clinical practice of healthcare professionals. Because individual decisions are often central to adoption of a clinical-related behaviour, more information about the cognitive mechanisms underlying behaviours is needed to improve behaviour change interventions targeting healthcare professionals. The aim of this study was to systematically review the published scientific literature about factors influencing health professionals' behaviours based on social cognitive theories. These theories refer to theories where individual cognitions/thoughts are viewed as processes intervening between observable stimuli and responses in real world situations.</p> <p>Methods</p> <p>We searched psycINFO, MEDLINE, EMBASE, CIHNAL, Index to theses, PROQUEST dissertations and theses and Current Contents for articles published in English only. We included studies that aimed to predict healthcare professionals' intentions and behaviours with a clear specification of relying on a social cognitive theory. Information on percent of explained variance (R²) was used to compute the overall frequency-weighted mean R²to evaluate the efficacy of prediction in several contexts and according to different methodological aspects. The cognitive factors most consistently associated with prediction of healthcare professionals' intention and behaviours were documented.</p> <p>Results</p> <p>Seventy eight studies met the inclusion criteria. Among these studies, 72 provided information on the determinants of intention and 16 prospective studies provided information on the determinants of behaviour. The theory most often used as reference was the Theory of Reasoned Action (TRA) or its extension the Theory of Planned Behaviour (TPB). An overall frequency-weighted mean R²of 0.31 was observed for the prediction of behaviour; 0.59 for the prediction of intention. A number of moderators influenced the efficacy of prediction; frequency-weighted mean R²varied from 0.001 to 0.58 for behaviour and 0.19 to 0.81 for intention.</p> <p>Conclusion</p> <p>Our results suggest that the TPB appears to be an appropriate theory to predict behaviour whereas other theories better capture the dynamic underlying intention. In addition, given the variations in efficacy of prediction, special care should be given to methodological issues, especially to better define the context of behaviour performance.</p