Using practice effects for targeted trials or sub-group analysis in Alzheimer\u27s disease: How practice effects predict change over time

OBJECTIVE: To describe the presence of practice effects in persons with Alzheimer disease (AD) or mild cognitive impairment (MCI) and to evaluate how practice effects affect cognitive progression and the outcome of clinical trials. METHODS: Using data from a meta-database consisting of 18 studies including participants from the Alzheimer disease Cooperative Study (ADCS) and the Alzheimer Disease Neuroimaging Initiative (ADNI) with ADAS-Cog11 as the primary outcome, we defined practice effects based on the improvement in the first two ADAS-Cog11 scores and then estimated the presence of practice effects and compared the cognitive progression between participants with and without practice effects. The robustness of practice effects was investigated using CDR SB, an outcome independent the definition itself. Furthermore, we evaluated how practice effects can affect sample size estimation. RESULTS: The overall percent of practice effects for AD participants was 39.0% and 53.3% for MCI participants. For AD studies, the mean change from baseline to 2 years was 12.8 points for the non-practice effects group vs 7.4 for the practice effects group; whereas for MCI studies, it was 4.1 for non-practice effects group vs 0.2 for the practice effects group. AD participants without practice effects progressed 0.9 points faster than those with practice effects over a period of 2 years in CDR-SB; whereas for MCI participants, the difference is 0.7 points. The sample sizes can be different by over 35% when estimated based on participants with/without practice effects. CONCLUSION: Practice effects were prevalent and robust in persons with AD or MCI and affected the cognitive progression and sample size estimation. Planning of future AD or MCI clinical trials should account for practice effects to avoid underpower or considers target trials or stratification analysis based on practice effects

Empirical validation of the S-Score algorithm in the analysis of gene expression data

BACKGROUND: Current methods of analyzing Affymetrix GeneChip(® )microarray data require the estimation of probe set expression summaries, followed by application of statistical tests to determine which genes are differentially expressed. The S-Score algorithm described by Zhang and colleagues is an alternative method that allows tests of hypotheses directly from probe level data. It is based on an error model in which the detected signal is proportional to the probe pair signal for highly expressed genes, but approaches a background level (rather than 0) for genes with low levels of expression. This model is used to calculate relative change in probe pair intensities that converts probe signals into multiple measurements with equalized errors, which are summed over a probe set to form the S-Score. Assuming no expression differences between chips, the S-Score follows a standard normal distribution, allowing direct tests of hypotheses to be made. Using spike-in and dilution datasets, we validated the S-Score method against comparisons of gene expression utilizing the more recently developed methods RMA, dChip, and MAS5. RESULTS: The S-score showed excellent sensitivity and specificity in detecting low-level gene expression changes. Rank ordering of S-Score values more accurately reflected known fold-change values compared to other algorithms. CONCLUSION: The S-score method, utilizing probe level data directly, offers significant advantages over comparisons using only probe set expression summaries

Area distribution of the planar random loop boundary

We numerically investigate the area statistics of the outer boundary of planar random loops, on the square and triangular lattices. Our Monte Carlo simulations suggest that the underlying limit distribution is the Airy distribution, which was recently found to appear also as area distribution in the model of self-avoiding loops.Comment: 10 pages, 2 figures. v2: minor changes, version as publishe

Does Job Stability Mediate the Relationship Between Intimate Partner Violence and Mental Health Among Low‐Income Women?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100283/1/ajop12053.pd

THE SPRING MIGRATION OF ADULT NORTH AMERICAN OSPREYS

Most North American Ospreys (Pandion haliaetus) are migratory, breeding in northern latitudes and migrating long distances to and from their wintering grounds in the tropics. Although fall migration patterns of North American Ospreys have been described and studied, very little has been published about the spring migration of these birds. We used satellite telemetry to: (1) determine the characteristics (timing, duration, migratory routes) of spring migrations of Ospreys; (2) determine if differences in spring migration patterns existed between sexes and among three breeding populations (east coast, midwestern, and western); and (3) compare consecutive fall and spring migrations of individual Ospreys. The median dates for departure from the wintering grounds and arrival on the breeding grounds did not differ significantly between adult male and female Ospreys. Compared to their fall migrations, all male and all east coast Ospreys spent fewer days on migration, fewer days in stopover periods along the migration route, traveled shorter distances overall, and traveled farther (on average) each day during spring. In contrast, fall and spring migration characteristics of all female and western Ospreys were similar. Our findings suggest that, although sex and breeding location might influence the spring migration strategy used by individual Ospreys, both males and females minimize the time spent on migration to ensure a timely arrival on the breeding grounds to establish or defend a nesting territory

Cognitive Behavioral Group Treatment for Social Phobia: Comparison with a Credible Placebo Control

Forty-nine patients participated in a study comparing cognitive-behavioral group treatment (CBGT) for social phobia with a credible placebo control. CBGT consisted of exposure to simulated phobic events, cognitive restructuring of maladaptive thoughts, and homework for self-directed exposure and cognitive restructuring between sessions. Control patients received a treatment package consisting of lecture-discussion and group support that was comparable to CBGT on measures of treatment credibility and outcome expectations. At pretest, posttest, and 3- and 6-month follow-ups, patients completed assessments that included clinician ratings, self-report measures, and behavioral physiological and cognitive-subjective measures derived from a behavioral simulation of a personally relevant phobic event. Both groups improved on most measures, but, at both posttest and follow-up, CBGT patients were rated as more improved than controls and reported less anxiety before and during the behavioral test. At follow-up, CBGT patients also reported significantly fewer negative and more positive self-statements than controls on a thought-listing task following the behavioral test. Regardless of treatment condition, follow-up changes in clinician-rated phobic severity were significantly related to changes on the thought-listing measure

Vaccines and Immunotherapeutics for the Treatment of Malignant Disease

The employment of the immune system to treat malignant disease represents an active area of biomedical research. The specificity of the immune response and potential for establishing long-term tumor immunity compels researchers to continue investigations into immunotherapeutic approaches for cancer. A number of immunotherapeutic strategies have arisen for the treatment of malignant disease, including various vaccination schemes, cytokine therapy, adoptive cellular therapy, and monoclonal antibody therapy. This paper describes each of these strategies and discusses some of the associated successes and limitations. Emphasis is placed on the integration of techniques to promote optimal scenarios for eliminating cancer

The escalating global burden of serious health-related suffering: projections to 2060 by world regions, age groups, and health conditions.

BACKGROUND: Serious life-threatening and life-limiting illnesses place an enormous burden on society and health systems. Understanding how this burden will evolve in the future is essential to inform policies that alleviate suffering and prevent health system weakening. We aimed to project the global burden of serious health-related suffering requiring palliative care until 2060 by world regions, age groups, and health conditions. METHODS: We projected the future burden of serious health-related suffering as defined by the Lancet Commission on Palliative Care and Pain Relief, by combining WHO mortality projections (2016-60) with estimates of physical and psychological symptom prevalence in 20 conditions most often associated with symptoms requiring palliative care. Projections were described in terms of absolute numbers and proportional change compared with the 2016 baseline data. Results were stratified by World Bank income regions and WHO geographical regions. FINDINGS: By 2060, an estimated 48 million people (47% of all deaths globally) will die with serious health-related suffering, which represents an 87% increase from 26 million people in 2016. 83% of these deaths will occur in low-income and middle-income countries. Serious health-related suffering will increase in all regions, with the largest proportional rise in low-income countries (155% increase between 2016 and 2060). Globally, serious health-related suffering will increase most rapidly among people aged 70 years or older (183% increase between 2016 and 2060). In absolute terms, it will be driven by rises in cancer deaths (16 million people, 109% increase between 2016 and 2060). The condition with the highest proportional increase in serious-related suffering will be dementia (6 million people, 264% increase between 2016 and 2060). INTERPRETATION: The burden of serious health-related suffering will almost double by 2060, with the fastest increases occurring in low-income countries, among older people, and people with dementia. Immediate global action to integrate palliative care into health systems is an ethical and economic imperative. FUNDING: Research Challenge Fund, Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London