Legislative Participation in the EU: An analysis of questions, speeches, motions and declarations in the 7th European Parliament

Which legislative activities in the European Parliament are ‘pluralistic’ – i.e. undertaken by all Members of the European Parliament, irrespective of legislative and electoral status? What type of parliamentary activity – if any – is dominated by party leaderships or vote-seekers in the European Union? This study will advance our knowledge of legislative politics in the EU by determining whether its legislature conforms to expectations from the legislative behaviour literature. This study compares the participation patterns in the EP7 (2009–2014) parliamentary questions, speeches, motions and written declarations via multilevel negative binomial regression. It makes use of a dataset on activity levels and demographics of 842 individual Members of the European Parliament serving between 2009 and 2014. The findings highlight that highly procedurally constrained activities, such as speeches and oral questions, are dominated by frontbenchers and vote-seekers, while procedurally ‘freer’ activities – written questions in particular – are very representative of the population of Members of the European Parliament. The analysis finds that there are both ‘pluralistic’ and vote-seeking activities in the ‘second order’ EU legislature, and that participation patterns broadly conform to patterns found in other established representative democracies

Pain assessment for people with dementia: a systematic review of systematic reviews of pain assessment tools.

BACKGROUND: There is evidence of under-detection and poor management of pain in patients with dementia, in both long-term and acute care. Accurate assessment of pain in people with dementia is challenging and pain assessment tools have received considerable attention over the years, with an increasing number of tools made available. Systematic reviews on the evidence of their validity and utility mostly compare different sets of tools. This review of systematic reviews analyses and summarises evidence concerning the psychometric properties and clinical utility of pain assessment tools in adults with dementia or cognitive impairment. METHODS: We searched for systematic reviews of pain assessment tools providing evidence of reliability, validity and clinical utility. Two reviewers independently assessed each review and extracted data from them, with a third reviewer mediating when consensus was not reached. Analysis of the data was carried out collaboratively. The reviews were synthesised using a narrative synthesis approach. RESULTS: We retrieved 441 potentially eligible reviews, 23 met the criteria for inclusion and 8 provided data for extraction. Each review evaluated between 8 and 13 tools, in aggregate providing evidence on a total of 28 tools. The quality of the reviews varied and the reporting often lacked sufficient methodological detail for quality assessment. The 28 tools appear to have been studied in a variety of settings and with varied types of patients. The reviews identified several methodological limitations across the original studies. The lack of a 'gold standard' significantly hinders the evaluation of tools' validity. Most importantly, the samples were small providing limited evidence for use of any of the tools across settings or populations. CONCLUSIONS: There are a considerable number of pain assessment tools available for use with the elderly cognitive impaired population. However there is limited evidence about their reliability, validity and clinical utility. On the basis of this review no one tool can be recommended given the existing evidence

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Contribution of Cystine-Glutamate Antiporters to the Psychotomimetic Effects of Phencyclidine

Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine–glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine–glutamate antiporters using the cysteine prodrug N-acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect that is blocked by N-acetylcysteine pretreatment. To determine the relevance of the above finding, we assessed social interaction and found that N-acetylcysteine reverses social withdrawal produced by repeated PCP. In a separate paradigm, acute PCP resulted in working memory deficits assessed using a discrete trial t-maze task, and this effect was also reversed by N-acetylcysteine pretreatment. The capacity of N-acetylcysteine to restore working memory was blocked by infusion of the cystine–glutamate antiporter inhibitor (S)-4-carboxyphenylglycine into the prefrontal cortex or systemic administration of the group II mGluR antagonist LY341495 indicating that the effects of N-acetylcysteine requires cystine–glutamate exchange and group II mGluR activation. Finally, protein levels from postmortem tissue obtained from schizophrenic patients revealed significant changes in the level of xCT, the active subunit for cystine–glutamate exchange, in the dorsolateral prefrontal cortex. These data advance cystine–glutamate antiporters as novel targets capable of reversing the psychotomimetic effects of PCP

Mycobacterium tuberculosis Growth following Aerobic Expression of the DosR Regulon

The Mycobacterium tuberculosis regulator DosR is induced by multiple stimuli including hypoxia, nitric oxide and redox stress. Overlap of these stimuli with conditions thought to promote latency in infected patients fuels a model in which DosR regulon expression is correlated with bacteriostasis in vitro and a proxy for latency in vivo. Here, we find that inducing the DosR regulon to wildtype levels in aerobic, replicating M. tuberculosis does not alter bacterial growth kinetics. We conclude that DosR regulon expression alone is insufficient for bacterial latency, but rather is expressed during a range of growth states in a dynamic environment

Impact of a Prohibitive Versus Restrictive Tobacco Policy on Liver Transplant Candidate Outcomes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150602/1/lt25497_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150602/2/lt25497.pd

RoB 2: a revised tool for assessing risk of bias in randomised trials

Assessment of risk of bias is regarded as an essential component of a systematic review on the effects of an intervention. The most commonly used tool for randomised trials is the Cochrane risk-of-bias tool. We updated the tool to respond to developments in understanding how bias arises in randomised trials, and to address user feedback on and limitations of the original tool

The Neural Organization of Semantic Control: TMS Evidence for a Distributed Network in Left Inferior Frontal and Posterior Middle Temporal Gyrus

Assigning meaning to words, sounds, and objects requires stored conceptual knowledge plus executive mechanisms that shape semantic retrieval according to the task or context. Despite the essential role of control in semantic cognition, its neural basis remains unclear. Neuroimaging and patient research has emphasized the importance of left inferior frontal gyrus (IFG)—however, impaired semantic control can also follow left temporoparietal lesions, suggesting that this function may be underpinned by a large-scale cortical network. We used repetitive transcranial magnetic stimulation in healthy volunteers to disrupt processing within 2 potential sites in this network—IFG and posterior middle temporal cortex. Stimulation of both sites selectively disrupted executively demanding semantic judgments: semantic decisions based on strong automatic associations were unaffected. Performance was also unchanged in nonsemantic tasks—irrespective of their executive demands—and following stimulation of a control site. These results reveal that an extended network of prefrontal and posterior temporal regions underpins semantic control

Prognostic significance of HER3 and HER4 protein expression in colorectal adenocarcinomas

BACKGROUND: Colorectal cancer remains a major cause of cancer mortality in the Western world. A limited number of studies has been conducted in respect of Her-3 and Her-4 expression and their correlation with clinical parameters and prognosis in colorectal carcinomas . In this study we sought to determine the pattern and the prognostic significance of HER-3 and HER-4 in colorectal adenocarcinoma. METHODS: We studied HER-3 and HER-4 protein expression in106 paraffin embedded specimens of primary colorectal tumors using immunohistochemistry. The pattern and protein expression levels of HER-3 and HER-4 were correlated with several clinical and pathological parameters. RESULTS: HER-3 staining displayed membranous and cytoplasmic expression pattern in 18 (17%) and 30 samples (28,3%), respectively. HER-4 membranous and cytoplasmic expression was found in 20 (18,9%) and 32 samples (30,2%), respectively. Specimens regarded as positive for HER-3 cytoplasmic expression were associated with moderate tumor grade (p = 0,032) and older median age (p = 0,010). Specimens regarded as positive for HER-4 membranous protein expression were associated with involved lymphnodes (p = 0,0003). Similar results were obtained when considering Her-3 and Her-4 protein expression irrespective of their cellular localization. There was no correlation between the expression of HER-3 and HER-4 and patients outcome. CONCLUSION: HER-4 membranous protein expression was found to predict for lymph nodes positivity in this cohort of patients with colorectal cancer.HER-4 expression status may identify tumors with aggressive biological behavior and increased metastatic potential

In Search of Cellular Immunophenotypes in the Blood of Children with Autism

Autism is a neurodevelopmental disorder characterized by impairments in social behavior, communication difficulties and the occurrence of repetitive or stereotyped behaviors. There has been substantial evidence for dysregulation of the immune system in autism.We evaluated differences in the number and phenotype of circulating blood cells in young children with autism (n = 70) compared with age-matched controls (n = 35). Children with a confirmed diagnosis of autism (4-6 years of age) were further subdivided into low (IQ<68, n = 35) or high functioning (IQ ≥ 68, n = 35) groups. Age- and gender-matched typically developing children constituted the control group. Six hundred and forty four primary and secondary variables, including cell counts and the abundance of cell surface antigens, were assessed using microvolume laser scanning cytometry.There were multiple differences in immune cell populations between the autism and control groups. The absolute number of B cells per volume of blood was over 20% higher for children with autism and the absolute number of NK cells was about 40% higher. Neither of these variables showed significant difference between the low and high functioning autism groups. While the absolute number of T cells was not different across groups, a number of cellular activation markers, including HLA-DR and CD26 on T cells, and CD38 on B cells, were significantly higher in the autism group compared to controls.These results support previous findings that immune dysfunction may occur in some children with autism. Further evaluation of the nature of the dysfunction and how it may play a role in the etiology of autism or in facets of autism neuropathology and/or behavior are needed