Miracle-dz/UniFAR-FTUs huggingface dataset:
Open Access Research Article Effectiveness of Strategies to Increase the Validity of Findings from Association Studies: Size vs. Replication

article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: The capacity of multiple comparisons to produce false positive findings in genetic association studies is abundantly clear. To address this issue, the concept of false positive report probability (FPRP) measures "the probability of no true association between a genetic variant and disease given a statistically significant finding". This concept involves the notion of prior probability of an association between a genetic variant and a disease, making it difficult to achieve acceptable levels for the FPRP when the prior probability is low. Increasing the sample size is of limited efficiency to improve the situation. Methods: To further clarify this problem, the concept of true report probability (TRP) is introduced by analogy to the positive predictive value (PPV) of diagnostic testing. The approach is extended to consider the effects of replication studies. The formula for the TRP after k replication studies is mathematically derived and shown to be only dependent on prior probability, alpha, power, and number of replication studies. Results: Case-control association studies are used to illustrate the TRP concept for replication strategies. Based on power considerations, a relationship is derived between TRP after k replication studies and sample size of each individual study. That relationship enables study designers optimization of study plans. Further, it is demonstrated that replication is efficient in increasing the TRP even in the case of low prior probability of an association and without requiring very large sample sizes for each individual study. Conclusions: True report probability is a comprehensive and straightforward concept for assessing the validity of positive statistical testing results in association studies. By its extension to replication strategies it can be demonstrated in a transparent manner that replication is highly effective in distinguishing spurious from true associations. Based on the generalized TRP method for replication designs, optimal research strategy and sample size planning become possible. Background The advent of the "omics" revolution caused molecular epidemiologists to attempt to rapidly identify as many associations between genetic variants (most often single nucleotide polymorphisms [SNPs]) and diseases as possible. In fact, discoveries were announced at impressive rates with respect to various diseases, particularly with the introduction of high-throughput genotyping technologies and genome-wide association studies. Hoover ([1], p. 14) speaks of a "blizzard of positive findings". This
Mortality in adults with and without diabetes: is the gap widening?

Objective We aimed to assess if the gap in mortality between adults with and without diabetes has widened over time in US adults. Methods and study design This cohort study included 44,041 adults with diabetes from the US National Health Interview Survey between 1986 and 2009 linked to the National Mortality Index data up to 2011. Each participant with diabetes was matched to two participants without diabetes by age, sex, race, survey year, and region of residence (88,082 persons without diabetes). Mortality differences and hazard ratios were calculated for different time periods defined by three methods, according to 1) survey years with original follow-up durations, 2) follow-up calendar years, and 3) survey years with a fixed 3-year follow-up duration. Results Different methods of defining time periods produced substantially different mortality rates and changing patterns over time. The decline in mortality was higher when time periods were defined according to survey years with original follow-up durations than with the fixed 3-year duration. Different time periods had comparable baseline and attained ages only when the fixed duration was used. With this method, the gap between adults with and without diabetes progressively decreased from 224 (95% confidence interval 188–260) in 1992–1994 to 99 (65–132) per 10,000 person-years in 2007–2009. Hazard ratios declined significantly from 2.12 (1.88–2.38) in 1995–1997 to 1.70 (1.44–2.00) in 2007–2009. Conclusion The decline in mortality over time was greater among adults with diabetes than those without diabetes. The gap in mortality between adults with diabetes and those without diabetes significantly narrowed in recent years, and was more than halved over the last 15 years.
Walking backwards into the future: a comparative perspective on education and a post-2015 framework

Introduction A good education emerges as the number one priority for the post-2015 world for the more than three million people around the world, who had voted by mid-2014 in the UN/civil society poll regarding the world we want (Myworld2015, 2014). In all, 2.3 million people had voted for a good education as one of the five most important aspirations for a post-2015 future. The other four top aspirations expressed in the votes cast by mid-2014 were better healthcare (1.9 million votes), an honest and responsive government (1.8 million), better job opportunities (1.7 million) and affordable and nutritious food (1.5 million). Those voting for a good education comprise men and women, all age groups, all income groups and all levels of education. The world we want is an educated world. As specialists in this field, the responsibilities of reflecting, revisiting and revisioning education for the world we want are considerable. What special perspective does a comparative approach to education bring? The argument I want to make is that much of the work on the Millennium Development Goals (MDGs), which focuses on enrolment and progression, takes too narrow a remit for why we do comparative education. Although the Education for All (EFA) Dakar Goals are broader than the MDGs (Sayed et al. 2013), they too have tended to work with attenuated perspectives on comparison, all too frequently merely comprising judgements about whether or not the gap has been bridged in a particular country between goals and their realisation. Thus, while much useful traction can be gained on the problem of children out of school or learning little within school, by looking at a limited range of issues, important insights are lost. These include insights into why the distribution of schooling is patterned in particular ways, the nature of the relationships between people, ideas and social formations, how and why particular people do ordinary and extraordinary things, what normative
Acquired Disorders of Reading and Writing: Cross-Script Comparisons

Aphasiologists have accumulated a sophisticated understanding of the language impairments among English speakers. Research in the field of cognitive neuropsychology has improved our knowledge about how language becomes impaired in English speakers following brain damage by generating conceptual frameworks for understanding why language impairments occur. A large proportion of the research evidence that supports these models comes from studies of patients who have acquired problems in spoken and written naming (anomia), reading (dyslexia) and writing (dysgraphia). The ultimate aim of this research is to enhance the lives of patients with aphasia by improving diagnosis of language impairments and by development of innovative rehabilitation strategies. One outstanding issue in the field is how to exploit our advances in knowledge to other languages. Crosslinguistic studies are rare but from what we do know there can be remarkably similar patterns of language impairment following damage to specific brain regions i.e., Broca’s and Wernicke’s areas that are known to be necessary for language comprehension and production [39,42,43]. However, the early work of pioneers such as Martin Albert, Liz Bates and Loraine Obler has taught us that communication disorders must be investigated in the context of the unique linguistic properties that characterize a particular language [1]. The challenge to researchers in the field of behavioural neurology is to document how these unique linguistic properties impact on specific communication abilities. Such reports may contribute to a cognitive neuropsychological framework used to interpret patterns of aphasia within languages. In addition to improving the lives of patients, this endeavor has the potential to lead to discoveries about how the brain adapts to different language environments. For example, we now know that distinct brain areas are implicated in dyslexia in different orthographies such as Chinese and English [54]. Much of the progress in our understanding of communication disorders in English comes from cognitive neuropsychological studies of patients with selective disorders of reading, spelling and writing. For example, acquired surface dyslexia in English refers to a selective impairment to the reading aloud of irregularly spelled words particularly if the words are low in frequency and have an abstract meaning e.g., indict. This impairment is accompanied by a preserved ability to read regularly spelled words and nonwords e.g. zint. Surface dyslexic reading is characterised by regularisation errors when reading word components e.g. yacht is pronounced ‘ya/tch/ed’. Acquired surface dysgraphic patients misspell irregularly spelled words e.g. yacht→ YOT and make homophone confusions in writing e.g. write the word stake when asked to write the sentence “He had steak for dinner”. The opposite pattern of reading impairment is acquired phonological dyslexia, which refers to impaired reading of nonwords together with a preserved ability to read irregular and regular
Complexity and Curriculum: A process approach to curriculum-making

It is argued that the complex learning with which higher education institutions are concerned is best promoted by coherent curricula. However, curriculum coherence is not widespread. Outcomes-led rational curriculum planning offers one way of creating coherent curricula, but it is argued that, despite its appeal, it is a poor approach to adopt. An alternative, process model of curriculum creation is described and claims are made about the advantages it can have as an approach to planning coherent learning programmes.
PTG protein depletion rescues malin‐deficient Lafora disease in mouse

Ubiquitin ligases regulate quantities and activities of target proteins, often pleiotropically. The malin ubiquitin E3 ligase is reported to regulate autophagy, the misfolded protein response, microRNA silencing, Wnt signaling, neuronatin‐mediated endoplasmic reticulum stress, and the laforin glycogen phosphatase. Malin deficiency causes Lafora disease, pathologically characterized by neurodegeneration and accumulations of malformed glycogen (Lafora bodies). We show that reducing glycogen production in malin‐deficient mice by genetically removing PTG, a glycogen synthesis activator protein, nearly completely eliminates Lafora bodies and rescues the neurodegeneration, myoclonus, seizure susceptibility, and behavioral abnormality. Glycogen synthesis downregulation is a potential therapy for the fatal adolescence onset epilepsy Lafora disease. Ann Neurol 2014;75:442–446
Oryza sativa Cytochrome P450 Family Member OsCYP96B4 Reduces Plant Height in a Transcript Dosage Dependent Manner

Background Plant cytochromes P450 are involved in a wide range of biosynthetic reactions and play various roles in plant development. However, little is known about the biological functions of the subfamily CYP96 in plants. Methodology/Principal Findings Here, we report a novel semi-dwarf rice mutant, in which a single copy of transposon dissociator (Ds) was inserted into the gene OsCYP96B4 (Oryza sativa Cytochrome P450 96B4). The mutant exhibits the defects in cell elongation and pollen germination, which can be complemented by the wild type OsCYP96B4 and be rescued by remobilization of the Ds element with the presence of the transposase Activator (Ac). Transgenic plants harboring OsCYP96B4 double-stranded RNA interference construct mimicked the mutant phenotype. The oscyp96b4 mutant phenotype could not be rescued by all the tested phytohormones and it was found that OsCYP96B4 reduced plant height in a transcript dosage dependent manner. Heterologous expression of OsCYP96B4 in Schizosaccharomyces pombe resulted in missegregation and wider cells. Further investigation showed that the mutant exhibited the defects in the metabolism of some lipid molecular species when compared with the wild type. Conclusions/Significance The oscyp96b4 mutant is a novel rice semi-dwarf mutant. Our data suggest that OsCYP96B4 might be involved in lipid metabolism and regulate cell elongation.
Early predictors of future reading skills: A follow-up of French-speaking children from the beginning of kindergarten to the end of the second grade (age 5 to 8)

We reported the results of two studies on the early predictors of future reading skills. The main goal of the first study was to examine whether reading level at age 8 can be predicted on the basis of a skill very rarely examined in longitudinal studies: phonemic discrimination. Two groups of French-speaking children were selected based on their phonemic discrimination skills at age 5: a group with low skills and a group with average to high skills in that domain. These two groups were respectively classified as being "at-risk" and "not-at-risk" for reading acquisition, and were matched on chronological age, nonverbal IQ and vocabulary. Phonemic discrimination was found to be an important predictor of reading acquisition. Indeed, the two groups defined at age 5 based on their phonemic discrimination skills obtained significantly different reading scores at age 8, and the proportion of children with reading disabilities was higher in the at-risk group than in the not-at-risk group. The main goal of the second study was to assess whether reading skills at age 8 could be predicted by the "classical" predictors of reading acquisition assessed at age 5: pre-reading level, letter-name knowledge, phonemic segmentation and phonological short-term-memory (STM). A high proportion of the variance in reading at age 8 (52.8%) was predicted by these predictors, with four contributing unique and significant portions of that variance: pre-reading level, letter-name knowledge for vowels (not for consonants), phonemic segmentation (not syllabic segmentation) and phonological STM.
The vastus lateralis muscle: An anatomical investigation

Anterior knee pain or patellofemoral pain syndrome is commonly encountered by clinicians, but the pathogenesis of this condition is not well understood. While much research has centred around the relationship between vastus medialis and anterior knee pain, little is known about the most lateral of the quadriceps muscle group, vastus lateralis (VL). Knowledge of the anatomical organization of VL is not only necessary to understand its precise function, but to also assist in the development of clinical and biomechanical models of knee dysfunction. The purpose of this study was to investigate the detailed morphology of VL, specifically to provide data relating to architecture, attachment sites, innervation, and the presence of anatomical partitioning within the muscle. The VL muscle was examined in 10 cadaveric lower limbs using macrodissection techniques. On the basis of architecture and innervation, this muscle comprised four partitions with each receiving its own unique nerve branch. The mean fascicular length of VL was 7 cm and the mean fascicular and muscle physiological cross‐sectional areas were 1.2 cm2 and 21.6 cm2, respectively. In addition to inserting proximally at the base of the greater trochanter and distally into the superolateral border and base of the patella, three additional attachment sites were identified: the lateral intermuscular septum, iliotibial band, and the rectus tendon. The results of this study suggest that the gross morphology of VL is more complex than previously described, and the information provided regarding architecture will contribute to knowledge regarding the function of VL as well as its role in knee joint dysfunction. Clin. Anat. 23:575–585, 2010. © 2010 Wiley‐Liss, Inc.
Public accountability: a new paradigm for college and university annual reports

Abstract This paper argues that the decision usefulness paradigm, which currently dominates accounting theory, is not an adequate basis for considering external reporting. A theoretical foundation is developed that draws upon older ideas of stewardship, as well as more recent notions of public accountability and social responsibility. The specific case of college and university reporting is used to delineate the impact a public accountability conceptual framework could have. The new paradigm is needed to address changes in society and in the environment of higher education in the US and other Western-style countries during the last three decades of the twentieth century. Numerous scandals and other dubious affairs involving even the most senior public officials has brought about an erosion of public confidence, and led to widespread demands for improved accountability by public officials and institutions. Comprehensive disclosures on the condition and performance of institutions would move college and university external reporting beyond decision usefulness and towards true public accountability.
Diagnostic information and adversity in childhood for offenders with learning disabilities referred to and accepted into forensic services

Several studies have related diagnostic information and adversity in childhood to criminal careers and risk of recidivism. Notably, ADHD and conduct disorder in childhood, schizophrenia, sexual abuse and physical abuse have been associated with offences in adulthood. This study investigates these variables in relation to large cohorts of offenders with learning disabilities. A case note review was undertaken for 126 individuals referred but not accepted into forensic learning disability services and 197 individuals accepted for such services. Results are reported on diagnostic information and experience of adversity in childhood. ADHD/conduct disorder featured prominently in both groups. Autistic spectrum disorders were not particularly over‐represented. For adversity in childhood, general socioeconomic deprivation featured prominently in both groups. This also increased significantly for those accepted into services. Sexual abuse and non‐accidental injury were featured at around 13‐20% for both groups. These results are broadly consistent with the mainstream literature on offending, ADHD/conduct disorder and general deprivation featuring significantly in all groups and rising for those accepted into offender services. It is important to deal with these aspects during assessment and to provide appropriate psychotherapeutic services for these individuals.
Estimation of time delays with fewer sensors than sources

A number of papers have been dealing with the problem of estimating the differential delay of an unknown signal impinging on two sensors. The present contribution deals with the presence of more than one source, which is a case that has never been dealt with before. The solution resorts to slices of high-order spectra, and the full spectral band of the signals is utilized in order to recover the delays. It can be viewed as an improvement to the classical procedure consisting of searching the autocorrelation for local maxima, which does not work when delays are smaller than the source correlation length.
Design criteria for children's Web portals: The users speak out

Four focus groups were held with young Web users (10 to 13 years of age) to explore design criteria for Web portals. The focus group participants commented upon four existing portals designed with young users in mind: Ask Jeeves for Kids, KidsClick, Lycos Zone, and Yahooligans! This article reports their first impressions on using these portals, their likes and dislikes, and their suggestions for improvements. Design criteria for children's Web portals are elaborated based upon these comments under four headings: portal goals, visual design, information architecture, and personalization. An ideal portal should cater for both educational and entertainment needs, use attractive screen designs based especially on effective use of color, graphics, and animation, provide both keyword search facilities and browsable subject categories, and allow individual user personalization in areas such as color and graphics.
An Efficient Algorithm for Non-Negative Matrix Factorization with Random Projections

Non-negative matrix factorization (NMF) is one of the most popular decomposition techniques for multivariate data. NMF is a core method for many machine-learning related computational problems, such as data compression, feature extraction, word embedding, recommender systems etc. In practice, however, its application is challenging for large datasets. The efficiency of NMF is constrained by long data loading times, by large memory requirements and by limited parallelization capabilities. Here we present a novel and efficient compressed NMF algorithm. Our algorithm applies a random compression scheme to drastically reduce the dimensionality of the problem, preserving well the pairwise distances between data points and inherently limiting the memory and communication load. Our algorithm supersedes existing methods in speed. Nonetheless, it matches the best non-compressed algorithms in reconstruction precision.
Determinism and stochasticity during maturation of the zebrafish antibody repertoire

It is thought that the adaptive immune system of immature organisms follows a more deterministic program of antibody creation than is found in adults. We used high-throughput sequencing to characterize the diversifying antibody repertoire in zebrafish over five developmental time points. We found that the immune system begins in a highly stereotyped state with preferential use of a small number of V (variable) D (diverse) J (joining) gene segment combinations, but that this stereotypy decreases dramatically as the zebrafish mature, with many of the top VDJ combinations observed in 2-wk-old zebrafish virtually disappearing by 1 mo. However, we discovered that, in the primary repertoire, there are strong correlations in VDJ use that increase with zebrafish maturity, suggesting that VDJ recombination involves a level of deterministic programming that is unexpected. This stereotypy is masked by the complex diversification processes of antibody maturation; the variation and lack of correlation in full repertoires between individuals appears to be derived from randomness in clonal expansion during the affinity maturation process. These data provide a window into the mechanisms of VDJ recombination and diversity creation and allow us to better understand how the adaptive immune system achieves diversity.