Seizure semiology of anti‐LGI1 antibody encephalitis

Limbic encephalitis associated with anti‐LGI1 antibody (LGI1 encephalitis) presents with a variety of features, the most prominent of which include seizures and progressive disturbance of memory and behaviour. Although varied in semiology, recognition of the pattern of seizures in LGI1 encephalitis is important, as early diagnosis and definitive treatment may prevent subsequent development of cognitive impairment. We present a patient with LGI1 encephalitis and “faciobrachial dystonic seizures‐plus”, which began as classic faciobrachial dystonic seizures and progressed to focal seizures with impaired awareness, dacrystic/gelastic‐like outbursts, ictal speech, manual automatisms, and autonomic signs (tachycardia). Recognition of the broad range of seizure types associated with LGI1 encephalitis is crucial for early diagnosis and definitive treatment. [Published with video sequence on www.epilepticdisorders.com]Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142082/1/epd212047.pd

Increasing late stage colorectal cancer and rectal cancer mortality demonstrates the need for screening: a population based study in Ireland, 1994-2010

BACKGROUND: This paper describes trends in colorectal cancer incidence, survival and mortality from 1994 to 2010 in Ireland prior to the introduction of population-based screening. METHODS: We examined incidence (National Cancer Registry Ireland (NCRI) and mortality (Central Statistics Office) from 1994 to 2010. Age standardised rates (ASR) for incidence and mortality have been calculated, weighted by the European standard population. Annual percentage change was calculated in addition to testing for linear trends in treatment and case fraction of early and late stage disease. Relative survival was calculated considering deaths from all causes. RESULTS: The colorectal cancer ASR was 63.7 per 100,000 in males and 38.7 per 100,000 in females in 2010. There was little change in the ASR over time in either sex, or when colon and rectal cancers were considered separately; however the number of incident cancers increased significantly during 1994-2010 (1752 to 2298). The case fractions of late stage (III/IV) colon and rectal cancers rose significantly over time. One and 5 year relative survival improved for both sexes between the periods 1994-2008. Colorectal cancer mortality ASRs decreased annually from 1994-2009 by 1.8% (95% CI -2.2, -1.4). Rectal cancer mortality ASRs rose annually by 2.4% (95% CI 1.1, 3.6) and 2.8% (95% CI 1.2, 4.4) in males and females respectively. CONCLUSIONS: Increases in late-stage disease and rectal cancer mortality demonstrate an urgent need for colorectal cancer screening. However, the narrow age range at which screening is initially being rolled-out in Ireland means that the full potential for reductions in late-stage cancers and incidence and mortality are unlikely to be achieved. While it is possible that the observed increase in rectal cancer mortality may be partly an artefact of cause of death misclassification, it could also be explained by variations in treatment and adherence to best practice guidelines; further investigation is warranted

Theology, News and Notes - Vol. 57, No. 01

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1166/thumbnail.jp

Cost-effectiveness of initial stress cardiovascular MR, stress SPECT or stress echocardiography as a gate-keeper test, compared with upfront invasive coronary angiography in the investigation and management of patients with stable chest pain: Mid-term outcomes from the CECaT randomised controlled trial

Objectives: To compare outcomes and cost-effectiveness of various initial imaging strategies in the management of stable chest pain in a long-term prospective randomised trial. Setting: Regional cardiothoracic referral centre in the east of England. Participants: 898 patients (69% man) entered the study with 869 alive at 2 years of follow-up. Patients were included if they presented for assessment of stable chest pain with a positive exercise test and no prior history of ischaemic heart disease. Exclusion criteria were recent infarction, unstable symptoms or any contraindication to stress MRI. Primary outcome measures: The primary outcomes of this follow-up study were survival up to a minimum of 2 years post-treatment, quality-adjusted survival and cost-utility of each strategy. Results: 898 patients were randomised. Compared with angiography, mortality was marginally higher in the groups randomised to cardiac MR (HR 2.6, 95% CI 1.1 to 6.2), but similar in the single photon emission CT-methoxyisobutylisonitrile (SPECT-MIBI; HR 1.0, 95% CI 0.4 to 2.9) and ECHO groups (HR 1.6, 95% CI 0.6 to 4.0). Although SPECT-MIBI was marginally superior to other non-invasive tests there were no other significant differences between the groups in mortality, quality-adjusted survival or costs. Conclusions: Non-invasive cardiac imaging can be used safely as the initial diagnostic test to diagnose coronary artery disease without adverse effects on patient outcomes or increased costs, relative to angiography. These results should be interpreted in the context of recent advances in imaging technology. Trial registration: ISRCTN 47108462, UKCRN 3696

A pharmacological network for lifespan extension in Caenorhabditis elegans

One goal of aging research is to find drugs that delay the onset of age-associated disease. Studies in invertebrates, particularly Caenorhabditis elegans, have uncovered numerous genes involved in aging, many conserved in mammals. However, which of these encode proteins suitable for drug targeting is unknown. To investigate this question, we screened a library of compounds with known mammalian pharmacology for compounds that increase C. elegans lifespan. We identified 60 compounds that increase longevity in C. elegans, 33 of which also increased resistance to oxidative stress. Many of these compounds are drugs approved for human use. Enhanced resistance to oxidative stress was associated primarily with compounds that target receptors for biogenic amines, such as dopamine or serotonin. A pharmacological network constructed with these data reveal that lifespan extension and increased stress resistance cluster together in a few pharmacological classes, most involved in intercellular signaling. These studies identify compounds that can now be explored for beneficial effects on aging in mammals, as well as tools that can be used to further investigate the mechanisms underlying aging in C. elegans

The role of area-level deprivation and gender in participation in population-based faecal immunochemical test (FIT) colorectal cancer screening

This study aimed to investigate the effects of sex and deprivation on participation in a population-based faecal immunochemical test (FIT) colorectal cancer screening programme. The study population included 9785 individuals invited to participate in two rounds of a population-based biennial FIT-based screening programme, in a relatively deprived area of Dublin, Ireland. Explanatory variables included in the analysis were sex, deprivation category of area of residence and age (at end of screening). The primary outcome variable modelled was participation status in both rounds combined (with “participation” defined as having taken part in either or both rounds of screening). Poisson regression with a log link and robust error variance was used to estimate relative risks (RR) for participation. As a sensitivity analysis, data were stratified by screening round. In both the univariable and multivariable models deprivation was strongly associated with participation. Increasing affluence was associated with higher participation; participation was 26% higher in people resident in the most affluent compared to the most deprived areas (multivariable RR = 1.26: 95% CI 1.21–1.30). Participation was significantly lower in males (multivariable RR = 0.96: 95%CI 0.95–0.97) and generally increased with increasing age (trend per age group, multivariable RR = 1.02: 95%CI, 1.01–1.02). No significant interactions between the explanatory variables were found. The effects of deprivation and sex were similar by screening round. Deprivation and male gender are independently associated with lower uptake of population-based FIT colorectal cancer screening, even in a relatively deprived setting. Development of evidence-based interventions to increase uptake in these disadvantaged groups is urgently required

Statistical and Probabilistic Extensions to Ground Operations' Discrete Event Simulation Modeling

NASA's human exploration initiatives will invest in technologies, public/private partnerships, and infrastructure, paving the way for the expansion of human civilization into the solar system and beyond. As it is has been for the past half century, the Kennedy Space Center will be the embarkation point for humankind's journey into the cosmos. Functioning as a next generation space launch complex, Kennedy's launch pads, integration facilities, processing areas, launch and recovery ranges will bustle with the activities of the world's space transportation providers. In developing this complex, KSC teams work through the potential operational scenarios: conducting trade studies, planning and budgeting for expensive and limited resources, and simulating alternative operational schemes. Numerous tools, among them discrete event simulation (DES), were matured during the Constellation Program to conduct such analyses with the purpose of optimizing the launch complex for maximum efficiency, safety, and flexibility while minimizing life cycle costs. Discrete event simulation is a computer-based modeling technique for complex and dynamic systems where the state of the system changes at discrete points in time and whose inputs may include random variables. DES is used to assess timelines and throughput, and to support operability studies and contingency analyses. It is applicable to any space launch campaign and informs decision-makers of the effects of varying numbers of expensive resources and the impact of off nominal scenarios on measures of performance. In order to develop representative DES models, methods were adopted, exploited, or created to extend traditional uses of DES. The Delphi method was adopted and utilized for task duration estimation. DES software was exploited for probabilistic event variation. A roll-up process was used, which was developed to reuse models and model elements in other less - detailed models. The DES team continues to innovate and expand DES capabilities to address KSC's planning needs

The impact of air-sea coupling and ocean biases on the seasonal cycle of southern West African precipitation

The biannual seasonal rainfall regime over the southern part of West Africa is characterised by two wet seasons, separated by the `Little Dry Season' in July-August. Lower rainfall totals during this intervening dry season may be detrimental for crop yields over a region with a dense population that depends on agricultural output. Coupled Model Intercomparison Project Phase 5 (CMIP5) models do not correctly capture this seasonal regime, and instead generate a single wet season, peaking at the observed timing of the Little Dry Season. Hence, the realism of future climate projections over this region is questionable. Here, the representation of the Little Dry Season in coupled model simulations is investigated, to elucidate factors leading to this misrepresentation. The Global Ocean Mixed Layer configuration of the Met Office Unified Model is particularly useful for exploring this misrepresentation, as it enables separating the effects of coupled model ocean biases in different ocean basins while maintaining air-sea coupling. Atlantic Ocean SST biases cause the incorrect seasonal regime over southern West Africa.Upper level descent in August reduces ascent along the coastline, which is associated with the observed reduction in rainfall during the Little Dry Season. When coupled model Atlantic Ocean biases are introduced, ascent over the coastline is deeper and rainfall totals are higher during July-August. Hence, this study indicates detrimental impacts introduced by Atlantic Ocean biases, and highlights an area of model development required for production of meaningful climate change projections over the West Africa region