422 research outputs found

    A prospective cohort study comparing the reactogenicity of trivalent influenza vaccine in pregnant and non-pregnant women

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    Background: Influenza vaccination during pregnancy can prevent serious illness in expectant mothers and provide protection to newborns; however, historically uptake has been limited due to a number of factors, including safety concerns. Symptomatic complaints are common during pregnancy and may be mistakenly associated with reactions to trivalent influenza vaccine (TIV). To investigate this, we compared post-vaccination events self-reported by pregnant women to events reported by non-pregnant women receiving TIV. Methods: A prospective cohort of 1,086 pregnant women and 314 non-pregnant female healthcare workers (HCWs) who received TIV between March-May 2014 were followed-up seven days post-vaccination to assess local and systemic adverse events following immunisation (AEFIs). Women were surveyed by text message regarding perceived reactions to TIV. Those reporting an AEFI completed an interview by telephone or mobile phone to ascertain details. Logistic regression models adjusting for age and residence were used to compare reactions reported by pregnant women and non-pregnant HCWs. Results: Similar proportions of pregnant women and non-pregnant, female HCWs reported ≥1 reaction following vaccination with TIV (13.0% and 17.3%, respectively; OR = 1.2 [95% CI: 0.8-1.8]). Non-pregnant, female HCWs were more likely to report fever or headache compared to pregnant women (OR: 4.6 [95% CI 2.1-10.3] and OR: 2.2 [95% CI 1.0-4.6], respectively). No other significant differences in reported symptoms were observed. No serious vaccine-associated adverse events were reported, and less than 2% of each group sought medical advice for a reaction. Conclusions: We found no evidence suggesting pregnant women are more likely to report adverse events following influenza vaccination when compared to non-pregnant female HCWs of similar age, and in some cases, pregnant women reported significantly fewer adverse events. These results further support the safety of TIV administered in pregnant women

    Induction of JNK and c-Abl signalling by cisplatin and oxaliplatin in mismatch repair-proficient and -deficient cells

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    Loss of DNA mismatch repair has been observed in a variety of human cancers. Recent studies have shown that loss of DNA mismatch repair results in resistance to cisplatin but not oxaliplatin, suggesting that the mismatch repair proteins serve as a detector for cisplatin but not oxaliplatin adducts. To identify the signal transduction pathways with which the detector communicates, we investigated the effect of loss of DNA mismatch repair on activation of known damage-responsive pathways, and recently reported that cisplatin differentially activates c-Jun NH2-terminal kinase (JNK) and c-Abl in repair-proficient vs.-deficient cells. In the current study, we directly compared differential activation of these pathways by cisplatin vs. oxaliplatin. The results confirm that cisplatin activates JNK kinase 5.7 ± 1.5 (s.d.)-fold more efficiently in DNA mismatch repair-proficient than repair-deficient cells, and that the c-Abl response to cisplatin is completely absent in DNA mismatch repair-deficient cells. In contrast, there was no detectable activation of the JNK or c-Abl kinases in DNA mismatch repair-proficient or -deficient cells exposed to oxaliplatin. The present study demonstrates that, despite the similarity of the adducts produced by cisplatin and oxaliplatin, they appear to be recognized by different detectors. The DNA mismatch repair system plays an important part in the recognition of cisplatin adducts, and activation of both the JNK and c-Abl kinases in response to cisplatin damage is dependent on the detector function of the DNA mismatch repair proteins. In contrast, this detector does not respond to oxaliplatin adducts. © 1999 Cancer Research Campaig

    A comparative assessment of the information technology services sector in India and China

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    The purpose of this paper is to assess the nature of competition in the information technology (IT) services sector between India and China. Using primary and secondary data sources, we compare and contrast the strengths and weaknesses of the IT services sector in the two countries along the main dimensions of Porter&rsquo;s competitive advantage model. The principal findings indicate that the IT services sectors in the two countries are distinctively different, have developed along different paths and are highly complementary to each other. China has a well established hardware sector and its IT services sector focuses mostly on servicing its domestic market. India&rsquo;s IT services sector is predominantly export orientated with focus on the US and Western European markets. Contrary to popular beliefs, given the complementary characteristics of the IT services sectors in India and China, it is unlikely for the two countries to compete against each other in the near future and greater strategic co-operation between IT service providers in the two countries is a more likely outcome.<br /

    Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage

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    This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non alcohol -induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular.and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed. Dysregulation of metabolism, as a result of ethanol exposure, in the intestine leads to colon carcinogenesis. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota have been suggested. The clinical aspects of NASH, as part of the metabolic syndrome in the aging population, have been presented. The symposium addressed mechanisms and biomarkers of alcohol induced damage to different organs, as well as the role of the microbiome in this dialog. The microbiota regulates and acts as a key element in harmonizing immune responses at intestinal mucosal surfaces. It is known that microbiota is an inducer of proinflammatory T helper 17 cells and regulatory T cells in the intestine. The signals at the sites of inflammation mediate recruitment and differentiation in order to remove inflammatory inducers and promote tissue homeostasis restoration. The change in the intestinal microbiota also influences the change in obesity and regresses the liver steatosis. Evidence on the positive role of moderate alcohol consumption on heart and metabolic diseases as well on reducing steatosis have been looked up. Moreover nutrition as a therapeutic intervention in alcoholic liver disease has been discussed. In addition to the original data, we searched the literature (2008-2016) for the latest publication on the described subjects. In order to obtain the updated data we used the usual engines (Pub Med and Google Scholar). The intention of the eighth symposia was to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

    The dilemma of arranged marriages in people with epilepsy. An expert group appraisal

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    INTRODUCTION: Matrimony remains a challenging psychosocial problem confronting people with epilepsy (PWE). People with epilepsy are less likely to marry; however, their marital prospects are most seriously compromised in arranged marriages. AIMS: The aim of this study was to document marital prospects and outcomes in PWE going through arranged marriage and to propose optimal practices for counseling PWE contemplating arranged marriage. METHODS: A MEDLINE search and literature review were conducted, followed by a cross-disciplinary meeting of experts to generate consensus. RESULTS: People with epilepsy experience high levels of felt and enacted stigma in arranged marriages, but the repercussions are heavily biased against women. Hiding epilepsy is common during marital negotiations but may be associated with poor medication adherence, reduced physician visits, and poor marital outcome. Although divorce rates are generally insubstantial in PWE, divorce rates appear to be higher in PWE undergoing arranged marriages. In these marriages, hiding epilepsy during marital negotiations is a risk factor for divorce. CONCLUSIONS: In communities in which arranged marriages are common, physicians caring for PWE are best-equipped to counsel them about their marital prospects. Marital plans and aspirations should be discussed with the family of the person with epilepsy in a timely and proactive manner. The benefits of disclosing epilepsy during marital negotiations should be underscored

    The second data release from the European Pulsar Timing Array IV. Search for continuous gravitational wave signals

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    We present the results of a search for continuous gravitational wave signals (CGWs) in the second data release (DR2) of the European Pulsar Timing Array (EPTA) collaboration. The most significant candidate event from this search has a gravitational wave frequency of 4-5 nHz. Such a signal could be generated by a supermassive black hole binary (SMBHB) in the local Universe. We present the results of a follow-up analysis of this candidate using both Bayesian and frequentist methods. The Bayesian analysis gives a Bayes factor of 4 in favor of the presence of the CGW over a common uncorrelated noise process, while the frequentist analysis estimates the p-value of the candidate to be 1%, also assuming the presence of common uncorrelated red noise. However, comparing a model that includes both a CGW and a gravitational wave background (GWB) to a GWB only, the Bayes factor in favour of the CGW model is only 0.7. Therefore, we cannot conclusively determine the origin of the observed feature, but we cannot rule it out as a CGW source. We present results of simulations that demonstrate that data containing a weak gravitational wave background can be misinterpreted as data including a CGW and vice versa, providing two plausible explanations of the EPTA DR2 data. Further investigations combining data from all PTA collaborations will be needed to reveal the true origin of this feature.Comment: 12 figures, 15 pages, to be submitte

    The second data release from the European Pulsar Timing Array III. Search for gravitational wave signals

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    We present the results of the search for an isotropic stochastic gravitational wave background (GWB) at nanohertz frequencies using the second data release of the European Pulsar Timing Array (EPTA) for 25 millisecond pulsars and a combination with the first data release of the Indian Pulsar Timing Array (InPTA). A robust GWB detection is conditioned upon resolving the Hellings-Downs angular pattern in the pairwise cross-correlation of the pulsar timing residuals. Additionally, the GWB is expected to yield the same (common) spectrum of temporal correlations across pulsars, which is used as a null hypothesis in the GWB search. Such a common-spectrum process has already been observed in pulsar timing data. We analysed (i) the full 24.7-year EPTA data set, (ii) its 10.3-year subset based on modern observing systems, (iii) the combination of the full data set with the first data release of the InPTA for ten commonly timed millisecond pulsars, and (iv) the combination of the 10.3-year subset with the InPTA data. These combinations allowed us to probe the contributions of instrumental noise and interstellar propagation effects. With the full data set, we find marginal evidence for a GWB, with a Bayes factor of four and a false alarm probability of 4%. With the 10.3-year subset, we report evidence for a GWB, with a Bayes factor of 60 and a false alarm probability of about 0.1% (≳3σ significance). The addition of the InPTA data yields results that are broadly consistent with the EPTA-only data sets, with the benefit of better noise modelling. Analyses were performed with different data processing pipelines to test the consistency of the results from independent software packages. The latest EPTA data from new generation observing systems show non-negligible evidence for the GWB. At the same time, the inferred spectrum is rather uncertain and in mild tension with the common signal measured in the full data set. However, if the spectral index is fixed at 13/3, the two data sets give a similar amplitude of (2.5 ± 0.7) × 10−15 at a reference frequency of 1 yr−1. Further investigation of these issues is required for reliable astrophysical interpretations of this signal. By continuing our detection efforts as part of the International Pulsar Timing Array (IPTA), we expect to be able to improve the measurement of spatial correlations and better characterise this signal in the coming years

    The second data release from the European Pulsar Timing Array: II. Customised pulsar noise models for spatially correlated gravitational waves

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    Aims. The nanohertz gravitational wave background (GWB) is expected to be an aggregate signal of an ensemble of gravitational waves emitted predominantly by a large population of coalescing supermassive black hole binaries in the centres of merging galaxies. Pulsar timing arrays (PTAs), which are ensembles of extremely stable pulsars at approximately kiloparsec distances precisely monitored for decades, are the most precise experiments capable of detecting this background. However, the subtle imprints that the GWB induces on pulsar timing data are obscured by many sources of noise that occur on various timescales. These must be carefully modelled and mitigated to increase the sensitivity to the background signal.Methods. In this paper, we present a novel technique to estimate the optimal number of frequency coefficients for modelling achromatic and chromatic noise, while selecting the preferred set of noise models to use for each pulsar. We also incorporated a new model to fit for scattering variations in the Bayesian pulsar timing package temponest. These customised noise models enable a more robust characterisation of single-pulsar noise. We developed a software package based on tempo2 to create realistic simulations of European Pulsar Timing Array (EPTA) datasets that allowed us to test the efficacy of our noise modelling algorithms.Results. Using these techniques, we present an in-depth analysis of the noise properties of 25 millisecond pulsars (MSPs) that form the second data release (DR2) of the EPTA and investigate the effect of incorporating low-frequency data from the Indian Pulsar Timing Array collaboration for a common sample of ten MSPs. We used two packages, enterprise and temponest, to estimate our noise models and compare them with those reported using EPTA DR1. We find that, while in some pulsars we can successfully disentangle chromatic from achromatic noise owing to the wider frequency coverage in DR2, in others the noise models evolve in a much more complicated way. We also find evidence of long-term scattering variations in PSR J1600-3053. Through our simulations, we identify intrinsic biases in our current noise analysis techniques and discuss their effect on GWB searches. The analysis and results discussed in this article directly help to improve the sensitivity to the GWB signal and they are already being used as part of global PTA efforts

    The second data release from the European Pulsar Timing Array: IV. Implications for massive black holes, dark matter, and the early Universe

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    The European Pulsar Timing Array (EPTA) and Indian Pulsar Timing Array (InPTA) collaborations have measured a low-frequency common signal in the combination of their second and first data releases, respectively, with the correlation properties of a gravitational wave background (GWB). Such a signal may have its origin in a number of physical processes including a cosmic population of inspiralling supermassive black hole binaries (SMBHBs); inflation, phase transitions, cosmic strings, and tensor mode generation by the non-linear evolution of scalar perturbations in the early Universe; and oscillations of the Galactic potential in the presence of ultra-light dark matter (ULDM). At the current stage of emerging evidence, it is impossible to discriminate among the different origins. Therefore, for this paper, we consider each process separately, and investigated the implications of the signal under the hypothesis that it is generated by that specific process. We find that the signal is consistent with a cosmic population of inspiralling SMBHBs, and its relatively high amplitude can be used to place constraints on binary merger timescales and the SMBH-host galaxy scaling relations. If this origin is confirmed, this would be the first direct evidence that SMBHBs merge in nature, adding an important observational piece to the puzzle of structure formation and galaxy evolution. As for early Universe processes, the measurement would place tight constraints on the cosmic string tension and on the level of turbulence developed by first-order phase transitions. Other processes would require non-standard scenarios, such as a blue-tilted inflationary spectrum or an excess in the primordial spectrum of scalar perturbations at large wavenumbers. Finally, a ULDM origin of the detected signal is disfavoured, which leads to direct constraints on the abundance of ULDM in our Galaxy
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