14 research outputs found

    Commissioners, guardians and paupers : life and death in the Limerick Poor Law Union, 1838-1850

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    It is accepted by historians of Ireland that British government response to the potato famine in the middle of the nineteenth century was inadequate. This dissertation examines that response in the Limerick Poor Law Union of Munster province. It demonstrates that the ideological underpinnings that provided the motivation for government response to poverty had evolved as the result of a debate which had been protracted and misguided. The result was a poor law system which assumed culpability on the part of the poor and a belief that the corrective was coercion. By focussing on the application of the law in a specific area, the dissertation demonstrates that the local Board of Guardians was powerless to mitigate the law's negative effects despite having serious misgivings about its impact. It puts into sharp focus the almost weekly dilemma which they faced of having to follow the directives of the Poor Law Commissioners or defy them in order to respond more appropriately to local needs. What really went on during the famine is better understood through case studies which specifically demonstrate the effects of government decision-making and the impact the resultant policy had in the daily lives of the people who received the intended services. The purpose of this case study is to amplify the findings of famine historians so that we can appreciate the human dimensions of the crisis

    Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

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    Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

    Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

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    Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

    Separating phonological and semantic processing in auditory sentence processing: A high-resolution event-related brain potential study

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    Phonological and semantic processing was studied using high-resolution event-related brain potentials (ERPs) during a sentence-matching task to investigate the spatial distribution of the phonological mismatch negativity (PMN) and the N400 response. It was hypothesized that the two components were spatially separable and that the activity matched prior localization knowledge. Participants examined visual-auditory sentence pairs that related within a semantic hierarchy (e.g., visual: "The man is teaching in the classroom"; Auditory: "The man is in the em leader school/barn"). Semantic congruency was varied for the final words of the spoken sentences. Incongruent words mismatched expectation in terms of both the initial phonological features (unexpected sound) and semantic features (unexpected meaning). In addition, the category-exemplar probability of the final words was either high or low, with low probability words being more difficult to anticipate. Low probability words were predicted to selectively affect PMN activity. We found that incongruent words elicited a PMN (287 msec) and a N400 (424 msec), for both the high and low probability words. As expected, low probability congruent words elicited a small PMN but no N400. In contrast, high probability congruent words elicited neither a detectible PMN nor a N400. The primary PMN sources were in left inferior frontal and inferior parietal lobes. The primary N400 source activation occurred along the left perisylvian cortex, consistent with prior N400 source localization work. From these results, it was concluded that the PMN and N400 were localized to separate cortical language (and memory) regions and had different source activation patterns.NRC publication: Ye

    Spatial MEG Laterality maps for language : clinical applications in epilepsy

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    Functional imaging is increasingly being used to provide a noninvasive alternative to intracarotid sodium amobarbitol testing (i.e., the Wada test). Although magnetoencephalography (MEG) has shown significant potential in this regard, the resultant output is often reduced to a simplified estimate of laterality. Such estimates belie the richness of functional imaging data and consequently limit the potential value. We present a novel approach that utilizes MEG data to compute \u201ccomplex laterality vectors\u201d and consequently \u201claterality maps\u201d for a given function. Language function was examined in healthy controls and in people with epilepsy. When compared with traditional laterality index (LI) approaches, the resultant maps provided critical information about the magnitude and spatial characteristics of lateralized function. Specifically, it was possible to more clearly define low LI scores resulting from strong bilateral activation, high LI scores resulting from weak unilateral activation, and most importantly, the spatial distribution of lateralized activation. We argue that the laterality concept is better presented with the inherent spatial sensitivity of activation maps, rather than being collapsed into a one-dimensional index.Peer reviewed: YesNRC publication: Ye

    Radicalism, republicanism and revolutionism

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    From Jeremy Bentham's radical philosophy to J. S. Mill's philosophic radicalism

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    Frontmatter

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    Social science from the French Revolution to positivism

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