Robustness of multiple testing procedures against dependence

An important aspect of multiple hypothesis testing is controlling the significance level, or the level of Type I error. When the test statistics are not independent it can be particularly challenging to deal with this problem, without resorting to very conservative procedures. In this paper we show that, in the context of contemporary multiple testing problems, where the number of tests is often very large, the difficulties caused by dependence are less serious than in classical cases. This is particularly true when the null distributions of test statistics are relatively light-tailed, for example, when they can be based on Normal or Student's $t$ approximations. There, if the test statistics can fairly be viewed as being generated by a linear process, an analysis founded on the incorrect assumption of independence is asymptotically correct as the number of hypotheses diverges. In particular, the point process representing the null distribution of the indices at which statistically significant test results occur is approximately Poisson, just as in the case of independence. The Poisson process also has the same mean as in the independence case, and of course exhibits no clustering of false discoveries. However, this result can fail if the null distributions are particularly heavy-tailed. There clusters of statistically significant results can occur, even when the null hypothesis is correct. We give an intuitive explanation for these disparate properties in light- and heavy-tailed cases, and provide rigorous theory underpinning the intuition.Comment: Published in at http://dx.doi.org/10.1214/07-AOS557 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

A programme theory for liaison mental health services in England

Background: Mechanisms by which liaison mental health services (LMHS) may bring about improved patient and organisational outcomes are poorly understood. A small number of logic models have been developed, but they fail to capture the complexity of clinical practice. Method: We synthesised data from a variety of sources including a large national survey, 73 in-depth interviews with acute and liaison staff working in hospitals with different types of liaison mental health services, and relevant local, national and international literature. We generated logic models for two common performance indicators used to assess organisational outcomes for LMHS: response times in the emergency department and hospital length of stay for people with mental health problems. Results: We identified 8 areas of complexity that influence performance, and 6 trade-offs which drove the models in different directions depending upon the balance of the trade-off. The logic models we developed could only be captured by consideration of more than one pass through the system, the complexity in which they operated, and the trade-offs that occurred. Conclusions: Our findings are important for commissioners of liaison services. Reliance on simple target setting may result in services that are unbalanced and not patient-centred. Targets need to be reviewed on a regular basis, together with other data that reflect the wider impact of the service, and any external changes in the system that affect the performance of LMHS, which are beyond their control

Effectiveness of an implementation optimisation intervention aimed at increasing parent engagement in HENRY, a childhood obesity prevention programme - the Optimising Family Engagement in HENRY (OFTEN) trial: study protocol for a randomised controlled trial

Background: Family-based interventions to prevent childhood obesity depend upon parents’ taking action to improve diet and other lifestyle behaviours in their families. Programmes that attract and retain high numbers of parents provide an enhanced opportunity to improve public health and are also likely to be more cost-effective than those that do not. We have developed a theory-informed optimisation intervention to promote parent engagement within an existing childhood obesity prevention group programme, HENRY (Health Exercise Nutrition for the Really Young). Here, we describe a proposal to evaluate the effectiveness of this optimisation intervention in regard to the engagement of parents and cost-effectiveness. Methods/design: The Optimising Family Engagement in HENRY (OFTEN) trial is a cluster randomised controlled trial being conducted across 24 local authorities (approximately 144 children’s centres) which currently deliver HENRY programmes. The primary outcome will be parental enrolment and attendance at the HENRY programme, assessed using routinely collected process data. Cost-effectiveness will be presented in terms of primary outcomes using acceptability curves and through eliciting the willingness to pay for the optimisation from HENRY commissioners. Secondary outcomes include the longitudinal impact of the optimisation, parent-reported infant intake of fruits and vegetables (as a proxy to compliance) and other parent-reported family habits and lifestyle. Discussion: This innovative trial will provide evidence on the implementation of a theory-informed optimisation intervention to promote parent engagement in HENRY, a community-based childhood obesity prevention programme. The findings will be generalisable to other interventions delivered to parents in other community-based environments. This research meets the expressed needs of commissioners, children’s centres and parents to optimise the potential impact that HENRY has on obesity prevention. A subsequent cluster randomised controlled pilot trial is planned to determine the practicality of undertaking a definitive trial to robustly evaluate the effectiveness and cost-effectiveness of the optimised intervention on childhood obesity prevention

Undelivered risk: A counter-factual analysis of the biosecurity risk avoided by inspecting international mail articles

International mail articles present an important potential vector for biosecurity and other regulatory risk. Border intervention is a key element in Australia’s biosecurity strategy. Arriving international mail articles are inspected and those that are intercepted with biosecurity risk material are documented, including the address to which the article was to be delivered. Knowledge about patterns in the intended destinations of mail article permits more detailed biosecurity intervention. We used geo-location software to identify the delivery address of mail articles intercepted with biosecurity risk material from 2008–2011. We matched these addresses with demographic data that were recorded at a regional level from the Australian Bureau of Statistics 2011 Census and used random forest statistical analyses to correlate various demographic fields at the regional level with the counts of seized mail articles. The analysis of the seizure counts against demographic characteristics suggests a high correlation between having higher numbers of university students that speak a particular language in a region and higher quantities of intercepted mail articles destined for that region. We also explore metropolitan and regional patterns in the destinations of seized materials. These results can be used to provide information on policy and operational actions to try to reduce the rate at which mail articles that contain biosecurity risk material are sent to Australia

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Angiotensin-converting enzyme activity and inhibition in dogs with cardiac disease and an angiotensin-converting enzyme polymorphism

OBJECTIVE The objective of this study was to evaluate angiotensin-converting enzyme (ACE) activity in dogs and with and without an ACE polymorphism in the canine ACE gene, before and after treatment with an ACE inhibitor. METHODS Thirty-one dogs (20 wild-type, 11 ACE polymorphism) with heart disease were evaluated with ACE activity measurement and systolic blood pressure before and after administration of an ACE inhibitor (enalapril). RESULTS Median pre-treatment ACE activity was significantly lower for ACE polymorphism dogs than for dogs with the wild-type sequence ( P=0.007). After two weeks of an ACE inhibitor, ACE activity was significantly reduced for both genotypes (wild-type, P<0.0001; ACE polymorphism P=0.03); mean post-therapy ACE activity was no different between the groups. CONCLUSION An ACE polymorphism is associated with lower levels of ACE activity. Dogs with the polymorphism still experience suppression of ACE activity in response to an ACE inhibitor. It is possible that the genetic status and ACE activity of dogs may impact the response of dogs with this variant to an ACE inhibitor

Assessing the impact of nitrogen supplementation in oats across multiple growth locations and years with targeted phenotyping and high-resolution metabolite profiling approaches

Oats (Avena sativa L.) are a healthy food, being high in dietary fibre (e.g. β-glucans), antioxidants, minerals, and vitamins. Understanding the effect of variety and crop management on nutritional quality is important. The response of four oat varieties to increased nitrogen levels was investigated across multiple locations and years with respect to yield, grain quality and metabolites (assessed via GC- and LC- MS). A novel high-resolution UHPLC-PDA-MS/MS method was developed, providing improved metabolite enrichment, resolution, and identification. The combined phenotyping approach revealed that, amino acid levels were increased by nitrogen supplementation, as were total protein and nitrogen containing lipid levels, whereas health-beneficial avenanthramides were decreased. Although nitrogen addition significantly increased grain yield and β-glucan content, supporting increasing the total nitrogen levels recommended within agricultural guidelines, oat varietal choice as well as negative impacts upon health beneficial secondary metabolites and the environmental burdens associated with nitrogen fertilisation, require further consideration

Expressions 1979

Expressions contains selected work from the 1979 Creative Writing Contest winners and honorable mentions along with Commercial Art students at Des Moines Area Community College. Design, typography and layout was done by Journalism students.https://openspace.dmacc.edu/expressions/1001/thumbnail.jp

Concert recording 2016-11-15

[Track 1]. Subjugation. Connection [Track 2]. Captivation / Durgan Maxey -- [Track 3]. Fight / Bryce Owens -- [Track 4]. Overture to Stay / Joshua Bland -- [Track 5]. A cellist\u27s legacy. Part I [Track 6]. Part II / Eric Dreggors -- [Track 7]. Evening prayer / Robbie Baker -- [Track 8]. Elegy / Brandon Wade -- [Track 9]. The grotesques trio. Gargoyles [Track 10]. Chimera [Track 11]. Grotesques / Marissa Johnson -- [Track 12]. Crosshair / Joshua Bland -- [Track 13]. Nightwind sings / L. Coley Pitchford -- [Track 14]. Six reflections through poetry. Memories (Walt Whitman) [Track 15]. The musician\u27s wife (Weldon Kees) [Track 16]. The road not taken (Robert Frost) [Track 17]. Lessons (Whitman) [Track 18]. Stronger lessons (Whitman) [Track 19]. O me! O life! (Whitman) / Nick Vecchio -- [Tracks 20-21]. String quartet #1 / Jeremiah Flannery -- [Track 22]. Tides. Morning tide [Track 23]. Bore tide / Elizabeth Greener -- [Track 24]. Shepherd\u27s contemplation / Robbie Baker -- Green grass / arranged by Eva Martin -- [Track 25]. Urbe fracta est II. A prayer for Jerusalem / Joshua Bland