New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P P = 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses. MTG

Goods or resource contests?

In this paper we analyze the optimal mix between appropriative and defensive activities for goods (goods contest) and appropriative and defensive activities for resources (resource contest). We show that goods contests are qualitatively different from resource contests. It turns out that for plausible cases the resource contest is dominated by the goods contest in the sense that investments are only positive in the latter. Copyright Springer Science+Business Media, LLC 2007Conflict, Anarchy, Goods, Resources,

Economies of scale in the production of swine manure Economias de escala na produção de dejetos de suínos

Manure production on grower/finisher swine operations in the United States was examined using data from 184 grower/finisher swine operations that participated in the United States National Animal Health Monitoring System's 1995 National Swine Study. Two methods were used: one, assuming that pigs produced 8.4% of their body weight in manure each day; another using the difference between feed fed and weight gained as a proxy variable to study manure production. Using this latter approach, a production function was developed. The function exhibited diminishing returns to scale when food waste was not fed to pigs, but constant returns to scale when food waste was included in their diets. The difference between feed fed and weight gained was lower on operations that restricted entry to employees only.<br>A produção de dejetos em granjas de crescimento e terminação de suínos nos Estados Unidos foi avaliada utilizando dados de 184 granjas participantes de um estudo nacional de 1995 do "United States National Animal Health Monitoring System". Dois métodos foram usados: um considerando que suínos produzem 8,4% do seu peso corporal de dejetos por dia e o outro usando a diferença entre o alimento ingerido e o ganho de peso como um indicador para o estudo da produção de esterco. Através desse último procedimento, desenvolveu-se uma função de produção