Controlled Postpartum-Newborn Simulation With Objective Evaluation Exchanged for Clinical Learning

Background: Simulation is a widely used teaching strategy. A paucity of evidence exist about evaluating acquisition of formal knowledge gained from simulation participation. This study compared practicing simulated assessments in the CSLC to practice in the clinical setting plus simulation, high/low level of student performance, and evaluated performance. Study variables were assessment, intervention, and critical thinking. Methods: Non-equivalent comparison group, post-test only quasi-experimental. 80 undergraduate nursing students individually demonstrated assessments while trained observer scored performance. Students provided written response to 7 questions before debriefing. T-tests, ANOVA, and MANOVA compared scores between the two groups. An outlier analysis operationalized high /low student performance. 92 points on both simulations equated to competent performance; lower scores required remediation. Results: No significant differences between the two groups on three study variables. A significant correlation found between postpartum and newborn psychomotor skills in high and low performing students. Average simulation performance score was 83 points. Conclusion: Well-designed simulation can be exchanged for learning in clinical, identify underperforming students, and evaluate performance qualit

MARV: a tool for genome-wide multi-phenotype analysis of rare variants

Background: Genome-wide association studies have enabled identification of thousands of loci for hundreds of traits. Yet, for most human traits a substantial part of the estimated heritability is unexplained. This and recent advances in technology to produce high-dimensional data cost-effectively have led to method development beyond standard common variant analysis, including single-phenotype rare variant and multi-phenotype common variant analysis, with the latter increasing power for locus discovery and providing suggestions of pleiotropic effects. However, there are currently no optimal methods and tools for the combined analysis of rare variants and multiple phenotypes. Results: We propose a user-friendly software tool MARV for Multi-phenotype Analysis of Rare Variants. The tool is based on a method that collapses rare variants within a genomic region and models the proportion of minor alleles in the rare variants on a linear combination of multiple phenotypes. MARV provides analyses of all phenotype combinations within one run and calculates the Bayesian Information Criterion to facilitate model selection. The running time increases with the size of the genetic data while the number of phenotypes to analyse has little effect both on running time and required memory. We illustrate the use of MARV with analysis of triglycerides (TG), fasting insulin (FI) and waist-to-hip ratio (WHR) in 4,721 individuals from the Northern Finland Birth Cohort 1966. The analysis suggests novel multi-phenotype effects for these metabolic traits at APOA5 and ZNF259, and at ZNF259 provides stronger support for association (P TG+FI = 1.8 × 10−9) than observed in single phenotype rare variant analyses (P TG = 6.5 × 10−8 and P FI = 0.27). Conclusions: MARV is a computationally efficient, flexible and user-friendly software tool allowing rapid identification of rare variant effects on multiple phenotypes, thus paving the way for novel discoveries and insights into biology of complex traits

Site fertility drives temporal turnover of vegetation at high latitudes

Experimental evidence shows that site fertility is a key modulator underlying plant community changes under climate change. Communities on fertile sites, with species having fast dynamics, have been found to react more strongly to climate change than communities on infertile sites with slow dynamics. However, it is still unclear whether this generally applies to high-latitude plant communities in natural environments at broad spatial scales. We tested a hypothesis that vegetation of fertile sites experiences greater changes over several decades and thus would be more responsive under contemporary climate change compared to infertile sites that are expected to show more resistance. We resurveyed understorey communities (vascular plants, bryophytes, and lichens) of four infertile and four fertile forest sites along a latitudinal bioclimatic gradient. Sites had remained outside direct human disturbance. We analyzed the magnitude of temporal community turnover, changes in the abundances of plant morphological groups and strategy classes, and changes in species diversity. In agreement with our hypothesis, temporal turnover of communities was consistently greater on fertile sites compared to infertile sites. However, our results suggest that the larger turnover of fertile communities is not primarily related to the direct effects of climatic warming. Furthermore, community changes in both fertile and infertile sites showed remarkable variation in terms of shares of plant functional groups and strategy classes and measures of species diversity. This further emphasizes the essential role of baseline environmental conditions and nonclimatic drivers underlying vegetation changes. Our results show that site fertility is a key determinant of the overall rate of high-latitude vegetation changes but the composition of plant communities in different ecological contexts is variously impacted by nonclimatic drivers over time.Peer reviewe

Alzheimer's disease pathology explains association between dementia with Lewy bodies and APOE-ε4/TOMM40 long poly-T repeat allele variants.

Introduction: The role of TOMM40-APOE 19q13.3 region variants is well documented in Alzheimer's disease (AD) but remains contentious in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Methods: We dissected genetic profiles within the TOMM40-APOE region in 451 individuals from four European brain banks, including DLB and PDD cases with/without neuropathological evidence of AD-related pathology and healthy controls. Results: TOMM40-L/APOE-ε4 alleles were associated with DLB (OR TOMM40 -L = 3.61; P value = 3.23 × 10-9; OR APOE -ε4 = 3.75; P value = 4.90 × 10-10) and earlier age at onset of DLB (HR TOMM40 -L = 1.33, P value = .031; HR APOE -ε4 = 1.46, P value = .004), but not with PDD. The TOMM40-L/APOE-ε4 effect was most pronounced in DLB individuals with concomitant AD pathology (OR TOMM40 -L = 4.40, P value = 1.15 × 10-6; OR APOE -ε4 = 5.65, P value = 2.97 × 10-8) but was not significant in DLB without AD. Meta-analyses combining all APOE-ε4 data in DLB confirmed our findings (ORDLB = 2.93, P value = 3.78 × 10-99; ORDLB+AD = 5.36, P value = 1.56 × 10-47). Discussion: APOE-ε4/TOMM40-L alleles increase susceptibility and risk of earlier DLB onset, an effect explained by concomitant AD-related pathology. These findings have important implications in future drug discovery and development efforts in DLB

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Reading during the composition of multi-sentence texts: an eye-movement study

Writers composing multi-sentence texts have immediate access to a visual representation of what they have written. Little is known about the detail of writers’ eye movements within this text during production. We describe two experiments in which competent adult writers’ eye-movements were tracked while performing short expository writing tasks. These are contrasted with conditions in which participants read and evaluated researcher-provided texts. Writers spent a mean of around 13% of their time looking back into their text. Initiation of these look-back sequences was strongly predicted by linguistically important boundaries in their ongoing production (e.g., writers were much more likely to look back immediately prior to starting a new sentence). 36% of look-back sequences were associated with sustained reading and the remainder with less patterned forward and backward saccades between words ("hopping"). Fixation and gaze durations and the presence of word-length effects suggested lexical processing of fixated words in both reading and hopping sequences. Word frequency effects were not present when writers read their own text. Findings demonstrate the technical possibility and potential value of examining writers’ fixations within their just-written text. We suggest that these fixations do not serve solely, or even primarily, in monitoring for error, but play an important role in planning ongoing production