Solutions for archiving data in long-term studies: A reply to Whitlock et al.

In our recent paper [1], we discussed some potential undesirable consequences of public data archiving (PDA) with specific reference to long-term studies and proposed solutions to manage these issues. We reaffirm our commitment to data sharing and collaboration, both of which have been common and fruitful practices supported for many decades by researchers involved in long-term studies. We acknowledge the potential benefits of PDA (e.g., [2]), but believe that several potential negative consequences for science have been underestimated [1] (see also 3 and 4). The objective of our recent paper [1] was to define practices to simultaneously maximize the benefits and minimize the potential unwanted consequences of PDA.

FTO genotype is associated with phenotypic variability of body mass index

There is evidence across several species for genetic control of phenotypic variation of complex traits1, 2, 3, 4, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ~170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)5, 6, 7, is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ~0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation9, 10. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

Meta-analysis of genome-wide association for migraine in six population-based European cohorts

Migraine is a common neurological disorder with a genetically complex background. This paper describes a meta-analysis of genome-wide association (GWA) studies on migraine, performed by the Dutch-Icelandic migraine genetics (DICE) consortium, which brings together six population-based European migraine cohorts with a total sample size of 10,980 individuals (2446 cases and 8534 controls). A total of 32 SNPs showed marginal evidence for association at a P-value<10(-5). The best result was obtained for SNP rs9908234, which had a P-value of 8.00 x 10(-8). This top SNP is located in the nerve growth factor receptor (NGFR) gene. However, this SNP did not replicate in three cohorts from the Netherlands and Australia. Of the other 31 SNPs, 18 SNPs were tested in two replication cohorts, but none replicated. In addition, we explored previously identified candidate genes in the meta-analysis data set. This revealed a modest gene-based significant association between migraine and the metadherin (MTDH) gene, previously identified in the first clinic-based GWA study (GWAS) for migraine (Bonferroni-corrected gene-based P-value=0.026). This finding is consistent with the involvement of the glutamate pathway in migraine. Additional research is necessary to further confirm the involvement of glutamate.

Members of the Godshaw (Gottschalk) family, Anne, Donald, Molly, Freddy, Jan and Hal; Hannover, Germany. Portraits Family

The family was in Hannover, Germany, for the dedication of the memorial to the Holocaust, the Mahnmal am Opernplatz; from left to right: Anne Godshaw nee Pick, Donald Godshaw, Molly Godshaw nee Peck, Freddy Godshaw, Jan Godshaw nee McKay, and Hal (Hans Ludwig Gottschalk) Godshaw.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10−9 to P = 1.8 × 10−40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10−3 to P = 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Structural studies of analgesics and their interactions. VII. Stereoisomerism and disorder in the structure of oxyphenbutazone monohydrate

Oxyphenbutazone, C19H20N203, a metabolite and perhaps the active form of phenylbutazone, is a widely used non-narcotic analgesic and anti-inflammatory pyrazolidinedione derivative. The monohydrate of the compound crystallizes in the triclinic space group Pi with two molecules in a unit cell of dimensions a -- 9.491 (4), b = 10.261 (5), c = 11.036 (3)A and ¢~ = 72.2 (1), fl = 64.3 (1), 7 = 73.0 (1) °. The structure was solved by direct methods and refined to an R value of 0.107 for 1498 observed reflections. The butyl group in the molecule is disordered. The hydroxyl group occupies two sites with unequal occupancies. On account of the asymmetry at the two N atoms and one of the C atoms in the central five-membered ring, the molecule can exist in eight isomeric states, of which four are sterically unfavourable. The disorder in the position of the hydroxyl group can be readily explained on the basis of the existence, with unequal abundances, of all four sterically favourable isomers.The bond lengths and angles in the molecule are similar to those in phenylbutazone. The crystal structure is stabilized by van der Waals interactions, and O-H... O hydrogen bonds involving the carbonyl and the hydroxyl groups as well as a water molecule.

The conservation status of the world’s reptiles

Effective and targeted conservation action requires detailed information about species, their distribution, systematics and ecology as well as the distribution of threat processes which affect them. Knowledge of reptilian diversity remains surprisingly disparate, and innovative means of gaining rapid insight into the status of reptiles are needed in order to highlight urgent conservation cases and inform environmental policy with appropriate biodiversity information in a timely manner. We present the first ever global analysis of extinction risk in reptiles, based on a random representative sample of 1500 species (16% of all currently known species). To our knowledge, our results provide the first analysis of the global conservation status and distribution patterns of reptiles and the threats affecting them, highlighting conservation priorities and knowledge gaps which need to be addressed urgently to ensure the continued survival of the world’s reptiles. Nearly one in five reptilian species are threatened with extinction, with another one in five species classed as Data Deficient. The proportion of threatened reptile species is highest in freshwater environments, tropical regions and on oceanic islands, while data deficiency was highest in tropical areas, such as Central Africa and Southeast Asia, and among fossorial reptiles. Our results emphasise the need for research attention to be focussed on tropical areas which are experiencing the most dramatic rates of habitat loss, on fossorial reptiles for which there is a chronic lack of data, and on certain taxa such as snakes for which extinction risk may currently be underestimated due to lack of population information. Conservation actions specifically need to mitigate the effects of human-induced habitat loss and harvesting, which are the predominant threats to reptiles.

Applicability of the van der Pauw-Hall measurement technique to implanted samples

The application of the van der Pauw-Hall measurement technique to implanted samples in which the mobility varies with depth has still not been fully justified. A proof that the technique is in fact applicable in this situation is given. Journal of Applied Physics is copyrighted by The American Institute of Physics.

Moving European research on work and ageing forward: Overview and agenda

This paper summarizes the state of affairs of European research on ageing and work. After a close inspection of the age construct, an overview is presented of research in four areas: the relationship between age and HR-policies, early retirement, age and performance/employability, age and health/well-being. The overview results in a research agenda on work and ageing and in recommendations for practice.

Development of a Multiplexed Bead-Based Suspension Array for the Detection and Discrimination of Pospiviroid Plant Pathogens

Efficient and reliable diagnostic tools for the routine indexing and certification of clean propagating material are essential for the management of pospiviroid diseases in horticultural crops. This study describes the development of a true multiplexed diagnostic method for the detection and identification of all nine currently recognized pospiviroid species in one assay using Luminex bead-based suspension array technology. In addition, a new data-driven, statistical method is presented for establishing thresholds for positivity for individual assays within multiplexed arrays. When applied to the multiplexed array data generated in this study, the new method was shown to have better control of false positives and false negative results than two other commonly used approaches for setting thresholds. The 11-plex Luminex MagPlex-TAG pospiviroid array described here has a unique hierarchical assay design, incorporating a near-universal assay in addition to nine species-specific assays, and a co-amplified plant internal control assay for quality assurance purposes. All assays of the multiplexed array were shown to be 100% specific, sensitive and reproducible. The multiplexed array described herein is robust, easy to use, displays unambiguous results and has strong potential for use in routine pospiviroid indexing to improve disease management strategies.

Use and usability of custom-made orthopedic shoes

The goal of this study was to investigate the use of custom-made orthopedic shoes (OS) and the association between the use of OS and the most relevant aspects of their usability. Over a 6-month period, patients meeting the inclusion criteria were recruited by 12 orthopedic shoe companies scattered throughout the Netherlands and asked to complete a questionnaire composed of a pre- and post-OS section. Patients with different pathologies were included in the study (n = 339; response 67%). Mean age of the patients was 63 +/- 15 years, and 38% were male. Three months after delivery, 81% of the patients used their OS frequently (4-7 days/week), 13% occasionally (1-3 days/week), and 6% did not use their OS. Associations were found between use and all measured aspects of usability (p-values varied from <0.001 to 0.028). Patients who used their OS more often had a more positive opinion regarding all the aspects of usability. We conclude that all aspects of the usability of OS are relevant in relation to their use and should be taken into account when prescribing and evaluating OS.

Patients' expectations and actual use of custom-made orthopaedic shoes

Objective: To investigate the association between patients' expectations and the actual use of custom-made orthopaedic shoes. Design: A prospective cohort study with internal comparison. Setting: Twelve orthopaedic shoe companies. Patients: During six months, consecutive patients who were provided with their first ever pair of orthopaedic shoes and aged 16 years or older were recruited. A total of 339 patients with different pathologies were included (response 67%). Mean (SD) age of the patients was 63 (15) years, and 129 patients (38%) were male. Main measures: A practical and reproducible questionnaire, measuring: frequency of use of orthopaedic shoes, patients' expectations and experiences of aspects of the usability of orthopaedic shoes, and communication about patients' expectations. Results: Patients' expectations were not associated with the use of orthopaedic shoes (P-values range: 0.106 to 0.607), but the difference between expectations and experiences was (P-values range: <0.001 to 0.012). The expectations of patients who frequently used their orthopaedic shoes were in concordance with their experiences, whereas the expectations of patients who did not use their orthopaedic shoes were much higher than their experiences. There was no communication of patients' expectations with the medical specialist or orthopaedic shoe technician in 34% and 25% of the patients respectively. Conclusions: In relation to the actual use of orthopaedic shoes, it is crucial that patients' expectations are not much higher than their experiences.

Long-term use of custom-made orthopedic shoes: A 1.5-year follow-up study

This study investigated long-term use of custom-made orthopedic shoes (OS) at 1.5 years follow-up. In addition, the association between short-term outcomes and long-term use was studied. Patients from a previously published study who did use their first-ever pair of OS 3 months after delivery received another questionnaire after 1.5 years. Patients with different pathologies were included in the study (n = 269, response = 86%). Mean age was 63 ± 14 years, and 38% were male. After 1.5 years, 87% of the patients still used their OS (78% frequently [4-7 days/week] and 90% occasionally [1-3 days/week]) and 13% of the patients had ceased using their OS. Patients who were using their OS frequently after 1.5 years had significantly higher scores for 8 of 10 short-term usability outcomes (p-values ranged from <0.001 to 0.046). The largest differences between users and nonusers were found for scores on the short-term outcomes of OS fit and communication with the medical specialist and shoe technician (effect size range = 0.16 to 0.46). We conclude that patients with worse short-term usability outcomes for their OS are more likely to use their OS only occasionally or not at all at long-term follow-up.

Development and reproducibility of a short questionnaire to measure use and usability of custom-made orthopaedic shoes

OBJECTIVE To develop a short and easy to use questionnaire to measure use and usability of custom-made orthopaedic shoes, and to investigate its reproducibility. DESIGN Development of the questionnaire (Monitor Orthopaedic Shoes) was based on a literature search, expert interviews, 2 expert meetings, and exploration and testing of reproducibility. The questionnaire comprises 2 parts: a pre part, measuring expectations; and a post part, measuring experiences. Patients The pre part of the final version was completed twice by 37 first-time users before delivery of their orthopaedic shoes. The post part of the final version was completed twice by 39 first-time users who had worn their orthopaedic shoes for 2–4 months. RESULTS High reproducibility scores (Cohen’s kappa > 0.60 or intra class correlation > 0.70) were found in all but one question of both parts of the final version of the Monitor Orthopaedic Shoes questionnaire. The smallest real difference on a visual analogue scale (100 mm) ranged from 21 to 50 mm. It took patients approximately 15 minutes to complete one part. CONCLUSION Monitor Orthopaedic Shoes is a practical and reproducible questionnaire that can measure relevant aspects of use and usability of orthopaedic shoes from a patient’s perspective.