Experimental reproducibility limits the correlation between mRNA and protein abundances in tumour proteomic profiles

Large-scale studies of human proteomes have revealed only a moderate correlation between mRNA and protein abundances. It is unclear to what extent this moderate correlation reflects post-transcriptional regulation and to what extent it reflects measurement error. Here, by analysing replicate proteomic profiles of tumour samples, we show that there is considerable variation in the reproducibility of measurements of individual proteins. We show that proteins with more reproducible measurements tend to have higher mRNA-protein correlation, suggesting that a substantial fraction of the unexplained variation between mRNA and protein abundances may be attributed to limitations in the reproducibility of proteomic quantification. We find that proteins that have high reproducibility in one study tend to have high reproducibility in others and exploit this to develop an 'aggregate protein reproducibility' score. This score can explain a substantial amount of the variation in mRNA-protein correlation across multiple studies of both healthy and tumour samples.

How can we categorise ‘nationality’ and ‘second generation’ in surveys without (re)producing stigmatisation?

Whilst reflexive migration studies have criticised the use of categories such as ‘nationality’ and ‘second generation’ in quantitative research, several gaps on how to develop such reflexivity remain. In qualitative data, the co-construction of knowledge seems feasible during fieldwork, whereas the deductive process of quantitative research limits such interactions and is more at risk of reproducing a ‘state thought’. Through a longitudinal database, the LIVES-FORS cohort survey of the National Center of Competence in Research LIVES – Overcoming Vulnerability: Life Course Perspectives and FORS – the Swiss Centre of Expertise in Social Sciences (herafter LCS), we engage in this discussion and provide some answers. The LCS is an annual longitudinal survey that, in 2013, started following a cohort of young adults born between 1988 and 1997 who grew up in Switzerland. The underlying hypothesis of the LCS is that migrants’ descendants have access to different resources (and often a lack thereof) to Swiss natives. In this paper, we discuss both the theoretical and empirical challenges to using the categories ‘nationality’ and ‘second generation’. We show the fluidity and subjectivity of these categories. By changing the definition of the category ‘second generation’, we increased the proportion of ‘second-generation’ participants from 43 to almost 62% of the sample. Looking across the five waves of the survey, we notice a 2% unexplained variation in the first nationality mentioned by the participants and 31% missing values regarding the nationality at birth – which are both indicators that nationality is a subjective category as well as a legal one. We illustrate that the static and neutral conceptions of these categories reproduce a false and stigmatised image of migrant descendants. To avoid these pitfalls we suggest developing multilevel geographical comparisons to consider the effects of time (age and historical), to use a wider range of information in order to be more precise, to examine different nationalities instead of focusing on the traditional nationalities of labour immigrants in a given country and to explore the reasons for the lack of answers to certain questions. Thus the questionnaires should include both more flexibility in the possibilities for answers and details and more-open questions regarding sensitive issues about the definition of the self. They should be developed through a participative and bottom-up process fostering mixed methods.

Parameters of Predicate Fronting

Many of the world’s languages permit or require clause-initial positioning of the primary predicate, potentially alongside some or all of its dependents. While such predicate fronting (where “fronting” may or may not involve movement) is a cross-linguistically widespread phenomenon, it is also subject to intricate and largely unexplained variation. The papers in this volume explore the empirical manifestations and theoretical modelling of predicate fronting across languages. There exists by now a rich literature on predicate fronting, but few attempts have been made at synthesizing the empirical observations and theoretical implementations that have emerged. While individual phenomena have been described in some detail, we are currently far from a complete understanding of the uniformity and variation underlying the wider cross-linguistic picture. The aim of the present volume is to take some steps towards this goal, by showcasing the state of the art in research on predicate fronting and the parameters governing its realization in a range of diverse languages.

How Big is the Ballpark? Assessing Variation in Grant Aid Awards within Net Price Calculator Student Profiles

Net Price Calculators (NPCs) are online tools designed to increase transparency in college pricing by presenting students with individualized estimates of net prices to attend a given postsecondary institution. The federal template NPC predicts identical aid awards for similarly-profiled students attending the same institution. Using the 2012 National Postsecondary Student Aid Survey, we use regression analysis to assess variation in actual financial aid awards among students predicted by the federal template NPC to receive identical awards. We find estimated aid, derived from the federal template NPC, accounts for 70 percent of the variation in actual grant aid received by students. We then consider modifications to the federal template NPC that include an additional upper income bracket option and indicators of both high school grade point average and Free Application for Federal Student Aid filing time. These modifications explain an additional 16 percentage points, or more than half, of the unexplained variation in actual grant aid awards across all institutional sectors. These findings are especially relevant as legislators consider policy efforts to bring greater transparency to college cost and pricing, including creating a universal NPC in which prospective students can enter information once to receive net price estimates at any institution.

The rise in women’s labour force participation in Mexico: Supply vs demand factors

We estimate the relative importance of alternative labour supply and demand mechanisms in explaining the rise of female labour force participation over the last 55 years in Mexico. The growth of female labour force participation in Mexico between 1960 and 2015 followed an S-shape, with a considerable acceleration during the 1990s. Using decomposition methods and a shift-share design, we show that, put together, supply and demand factors can account for the rise of female labour force participation over the period, led by increases in women’s education and shifts in the occupational structure of the workforce. However, there is unexplained variation in the 1990s, when female labour force participation spiked.

The Landscape of Differential Attainment in Medicine

Differential attainment is the unexplained variation in results in assessment, training, and recruitment outcomes seen in candidates based on factors other than academic ability when compared to their peers. This is seen in both the medical school curriculum and in many professions beyond. It is an unfortunate fact that in spite of recognition and awareness at a systemic level, there is little if any resolution. DA must be recognised as a systemic bias rather than an individual issue. More research into the causes is required, as well as the implementation and evaluation of potential solutions. Interventions need to be made in the learning environment, culture, educational governance, leadership, support for educators, in the development of responsive curricula and fair assessments. In order to build a fairer training system, it is important that we review and act on existing inequality through organisational change.

K ETYMOLOGIJI PSŁ. *SLĚPЪ/SLEPЪ

This article explains the hitherto unexplained variation of the root *slep/slěp- ‘blind’ which results from an old opposition of the causative (lengthened grade) vs. regular root (regular grade). This indicates a connection with the Lithuanian silpnas as a zero-grade root for the Slavic word which previously had no convincing parallels in other languages. Semantically, a connection with words meaning ‘sticky’ (as postulated by Šewc 1978 and others) should be rejected: they are neither phonetically nor semantically convincing. The preference is for the interpretation of blindness as a special kind of weakness.

Antibiotic use and deprivation: an analysis of Welsh primary care antibiotic prescribing data by socioeconomic status

Objectives To examine the association between socioeconomic status (SES) and antibiotic prescribing, controlling for the presence of common chronic conditions and other potential confounders and variation amongst GP practices and clusters. Methods This was an electronic cohort study using linked GP and Welsh Index of Multiple Deprivation (WIMD) data. The setting was GP practices contributing to the Secure Anonymised Information Linkage (SAIL) Databank 2013–17. The study involved 2.9 million patients nested within 339 GP practices, nested within 67 GP clusters. Results Approximately 9 million oral antibiotics were prescribed between 2013 and 2017. Antibiotic prescribing rates were associated with WIMD quintile, with more deprived populations receiving more antibiotics. This association persisted after controlling for patient demographics, smoking, chronic conditions and clustering by GP practice and cluster, with those in the most deprived quintile receiving 18% more antibiotic prescriptions than those in the least deprived quintile (incidence rate ratio = 1.18; 95% CI = 1.181–1.187). We found substantial unexplained variation in antibiotic prescribing rates between GP practices [intra-cluster correlation (ICC) = 47.31%] and GP clusters (ICC = 12.88%) in the null model, which reduced to ICCs of 3.50% and 0.85% for GP practices and GP clusters, respectively, in the final adjusted model. Conclusions Antibiotic prescribing in primary care is increased in areas of greater SES deprivation and this is not explained by differences in the presence of common chronic conditions or smoking status. Substantial unexplained variation in prescribing supports the need for ongoing antimicrobial stewardship initiatives.

Exploring geographic variation of and influencing factors for utilization of four diabetes management measures in Swiss population using claims data

IntroductionFour strongly recommended diabetes management measures are biannual glycated hemoglobin (HbA1c) testing, annual eye examination, kidney function examination, and low-density lipoprotein (LDL) testing in patients below 75 years. We aimed to describe regional variation in the utilization of the four measures across small regions in Switzerland and to explore potential influencing factors.Research design and methodsWe conducted a cross-sectional study of adult patients with drug-treated diabetes in 2014 using claims data. Four binary outcomes represented adherence to the recommendations. Possible influencing factors included sociodemographics, health insurance preferences, and clinical characteristics. We performed multilevel modeling with Medstat regions as the higher level. We calculated the median odds ratio (MOR) and checked spatial autocorrelation in region level residuals using Moran’s I statistic. When significant, we further conducted spatial multilevel modeling.ResultsOf 49 198 patients with diabetes (33 957 below 75 years), 69.6% had biannual HbA1c testing, 44.3% each had annual eye examination and kidney function examination, and 55.5% of the patients below 75 years had annual LDL testing. The effects of health insurance preferences were substantial and consistent. Having any supplementary insurance (ORs across measures were between 1.08 and 1.28), having supplementary hospital care insurance (1.08–1.30), having chosen a lower deductible level (eg, SFr2500 compared with SFr300: 0.57–0.69), and having chosen a managed care model (1.04–1.17) were positively associated with recommendations adherence. The MORs (1.27–1.33) showed only moderate unexplained variation, and we observed inconsistent spatial patterns of unexplained variation across the four measures.ConclusionOur findings indicate that the uptake of strongly recommended measures in diabetes management could possibly be optimized by providing further incentives to patients and care providers through insurance scheme design. The absence of marked regional variation implies limited potential for improvement by targeted regional intervention, while provider-specific promotion may be more impactful.

Increased juvenile survival may not be universally linked to longevity: ecological, social and life-history drivers of age-specific mortality in birds

A classical prediction of the traditional evolutionary theories of ageing (tETA) is that longevity should be positively correlated with survival early on in life. However, large and unexplained variation exists in juvenile survival-longevity combinations. Here, we provide the first comparative study investigating the life-history, ecological and social correlates of juvenile survival, longevity and their combinations in 204 bird species. Overall, both measurements were positively correlated, but multiple survivals’ combinations evolved, some in accordance with tETA (“positive JS-L combinations”) while others contrasting it (“JS-L mismatches”). Positive JS-L combinations covaried with the pace of life proxies, whereas mismatching combinations covaried with the growing season length, where long growing seasons promoted juvenile survival, while short growing seasons promoted longevity. Interestingly, sociality explained only positive combinations, while life-history and ecological traits explained both positive and mismatching combinations. Overall, these findings challenge a main prediction of the tETA, and identify key evolutionary forces driving the coevolution between juvenile survival and longevity.