Prospective memory functioning among ecstasy/polydrug users: evidence from the Cambridge Prospective Memory Test (CAMPROMPT)

Rationale: Prospective memory (PM) deficits in recreational drug users have been documented in recent years. However, the assessment of PM has largely been restricted to self-reported measures that fail to capture the distinction between event-based and time-based PM. The aim of the present study is to address this limitation. Objectives: Extending our previous research, we augmented the range laboratory measures of PM by employing the CAMPROMPT test battery to investigate the impact of illicit drug use on prospective remembering in a sample of cannabis only, ecstasy/polydrug and non-users of illicit drugs, separating event and time-based PM performance. We also administered measures of executive function and retrospective memory in order to establish whether ecstasy/polydrug deficits in PM were mediated by group differences in these processes. Results: Ecstasy/polydrug users performed significantly worse on both event and time-based prospective memory tasks in comparison to both cannabis only and non-user groups. Furthermore, it was found that across the whole sample, better retrospective memory and executive functioning was associated with superior PM performance. Nevertheless, this association did not mediate the drug-related effects that were observed. Consistent with our previous study, recreational use of cocaine was linked to PM deficits. Conclusions: PM deficits have again been found among ecstasy/polydrug users, which appear to be unrelated to group differences in executive function and retrospective memory. However, the possibility that these are attributable to cocaine use cannot be excluded

Detecting a conditional extrme value model

In classical extreme value theory probabilities of extreme events are estimated assuming all the components of a random vector to be in a domain of attraction of an extreme value distribution. In contrast, the conditional extreme value model assumes a domain of attraction condition on a sub-collection of the components of a multivariate random vector. This model has been studied in \cite{heffernan:tawn:2004,heffernan:resnick:2007,das:resnick:2008a}. In this paper we propose three statistics which act as tools to detect this model in a bivariate set-up. In addition, the proposed statistics also help to distinguish between two forms of the limit measure that is obtained in the model.Comment: 21 pages, 4 figure

Estimation of conditional laws given an extreme component

Let $(X,Y)$ be a bivariate random vector. The estimation of a probability of the form $P(Y\leq y \mid X >t)$ is challenging when $t$ is large, and a fruitful approach consists in studying, if it exists, the limiting conditional distribution of the random vector $(X,Y)$, suitably normalized, given that $X$ is large. There already exists a wide literature on bivariate models for which this limiting distribution exists. In this paper, a statistical analysis of this problem is done. Estimators of the limiting distribution (which is assumed to exist) and the normalizing functions are provided, as well as an estimator of the conditional quantile function when the conditioning event is extreme. Consistency of the estimators is proved and a functional central limit theorem for the estimator of the limiting distribution is obtained. The small sample behavior of the estimator of the conditional quantile function is illustrated through simulations.Comment: 32 pages, 5 figur

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

The persisting burden of invasive pneumococcal disease in HIV patients: an observational cohort study

<p>Abstract</p> <p>Background</p> <p>The increasing use of highly active antiretroviral therapy (HAART) and pneumococcal immunization along with shifting community exposures may have altered the burden of <it>Streptococcus pneumoniae </it>disease in HIV-infected persons. We describe the burden and risk factors for pneumococcal disease in the modern era of HIV care and evaluate the use of a 23-valent pneumococcal polysaccharide vaccine (PPV-23).</p> <p>Methods</p> <p>The incidence of invasive pneumococcal disease (IPD) between January 1^st, 2000 and January 1^st, 2010 in a regional HIV population in Southern Alberta, Canada was determined by linking comprehensive laboratory and hospital surveillance data. Clinical and epidemiologic data including risk factors for <it>S. pneumoniae</it>, history of pneumococcal immunization, serotypes of infections, and length of any hospitalizations for pneumococcal disease were evaluated with multivariate analysis. CD4 count and viral load at immunization were evaluated with a nested case-control analysis.</p> <p>Results</p> <p>In 1946 HIV-patients with 11,099 person-years of follow up, there were 68 distinct episodes of pneumococcal disease occurring in 50 patients. Increased risk was seen if female, age >60, Aboriginal ethnicity, lower education, injection drug use, smoking, nadir CD4 <200/μL, chronic obstructive pulmonary disease, and hepatitis C. Overall, the incidence of IPD was 342/100,000 person-years and was reduced to 187/100,000 within three years of PPV-23 immunization (P < 0.01). Although 78% of patients received PPV-23, 74% of IPD episodes were caused by PPV-23 serotypes. In a case-control analysis, HIV viral load at immunization was significantly predictive of PPV-23 failure, while CD4 count was not. 80% of IPD cases required hospitalization: median length of stay was 7 days (range: 1-71); four patients died.</p> <p>Conclusions</p> <p>Despite universal access to intensive measures to prevent pneumococcal disease including the widespread use of HAART and PPV-23 immunization, the incidence of IPD remains high in HIV patients with its associated morbidity and mortality.</p

A Model of Salmonella Colitis with Features of Diarrhea in SLC11A1 Wild-Type Mice

Background: Mice do not get diarrhea when orally infected with S. enterica, but pre-treatment with oral aminoglycosides makes them susceptible to Salmonella colitis. However, genetically susceptible ItyS mice (Nramp1 G169D allele) die from systemic infection before they develop diarrhea, so a new model is needed to study the pathogenesis of diarrhea. We pretreated ItyR mice (Nramp1 G169) with oral kanamycin prior to infecting them with virulent S. Typhimurium strain 14028s in order to study Salmonella-induced diarrhea. We used both a visual scoring system and the measurement of fecal water content to measure diarrhea. BALB/c.D2 Nramp1 congenic started losing weight 5 days post-infection and they began to die from colitis 10–14 days after infection. A SPI-1 (invA) mutant caused cecal, but not colonic inflammation and did not cause diarrhea. A phoP- mutant did not cause manifestations of diarrhea in either normal or NADPHdeficient (gp91 phox) mice. However, strain 14028s caused severe colitis and diarrhea in gp91 phox-deficient mice on an ItyR background. pmr A and F mutants, which are less virulent in orally infected BALB/c mice, were fully virulent in this model of colitis. Conclusions: S. enterica must be able to invade the colonic epithelium and to persist in the colon in order to cause colitis with manifestations of diarrhea. The NADPH oxidase is not required for diarrhea in Salmonella colitis. Furthermore,

Collaboration and knowledge exchange between scholars in Britain and the empire, 1830–1914

In recent years there has been a growing interest among historians in the British Empire as a space of knowledge production and circulation. Much of this work assumes that scholarly cooperation and collaboration between individuals and institutions within the Empire had the effect (and often also the aim) of strengthening both imperial ties and the idea of empire. This chapter argues, however, that many examples of scholarly travel, exchange, and collaboration were undertaken with very different goals in mind. In particular, it highlights the continuing importance of an ideal of scientific internationalism, which stressed the benefits of scholarship for the whole of humanity and prioritized the needs and goals of individual academic and scientific disciplines. As the chapter shows, some scholars even went on to develop nuanced critiques of the imperial project while using the very structures of empire to further their own individual, disciplinary and institutional goals

Estimating the Duration of Pertussis Immunity Using Epidemiological Signatures

Case notifications of pertussis have shown an increase in a number of countries with high rates of routine pediatric immunization. This has led to significant public health concerns over a possible pertussis re-emergence. A leading proposed explanation for the observed increase in incidence is the loss of immunity to pertussis, which is known to occur after both natural infection and vaccination. Little is known, however, about the typical duration of immunity and its epidemiological implications. Here, we analyze a simple mathematical model, exploring specifically the inter-epidemic period and fade-out frequency. These predictions are then contrasted with detailed incidence data for England and Wales. We find model output to be most sensitive to assumptions concerning naturally acquired immunity, which allows us to estimate the average duration of immunity. Our results support a period of natural immunity that is, on average, long-lasting (at least 30 years) but inherently variable