Using Regular Languages to Explore the Representational Capacity of Recurrent Neural Architectures

The presence of Long Distance Dependencies (LDDs) in sequential data poses significant challenges for computational models. Various recurrent neural architectures have been designed to mitigate this issue. In order to test these state-of-the-art architectures, there is growing need for rich benchmarking datasets. However, one of the drawbacks of existing datasets is the lack of experimental control with regards to the presence and/or degree of LDDs. This lack of control limits the analysis of model performance in relation to the specific challenge posed by LDDs. One way to address this is to use synthetic data having the properties of subregular languages. The degree of LDDs within the generated data can be controlled through the k parameter, length of the generated strings, and by choosing appropriate forbidden strings. In this paper, we explore the capacity of different RNN extensions to model LDDs, by evaluating these models on a sequence of SPk synthesized datasets, where each subsequent dataset exhibits a longer degree of LDD. Even though SPk are simple languages, the presence of LDDs does have significant impact on the performance of recurrent neural architectures, thus making them prime candidate in benchmarking tasks.Comment: International Conference of Artificial Neural Networks (ICANN) 201

Management of type II superior labrum anterior posterior lesions: a review of the literature

Superior labrum anterior and posterior lesions were first described in 1985 by Andrews et al. and later classified into four types by Synder et al. The most prevalent is type II which is fraying of the superior glenoid labrum with detachment of the biceps anchor. Superior labrum anterior posterior (SLAP) lesions can also be associated with other shoulder pathology. Both MRI and MRA can be utilized in making the diagnosis with the coronal images being the most sensitive. The mechanism of injury can be either repetitive stress or acute trauma with the superior labrum most vulnerable to injury during the late cocking phase of throwing. A combination of the modified dynamic labral shear and O'Brien test can be used clinically in making the diagnosis of SLAP lesion. However, the most sensitive and specific test used to diagnosis specifically a type II SLAP lesion is the Biceps Load Test II. The management of type II SLAP lesions is controversial and dependent on patient characteristics. In the young high demanding overhead athlete, repair of the type II lesion is recommended to prevent glenohumeral instability. In middle-aged patients (age 25–45), repair of the type II SLAP lesion with concomitant treatment of other shoulder pathology resulted in better functional outcomes and patient satisfaction. Furthermore, patients who had a distinct traumatic event resulting in the type II SLAP tear did better functionally than patients who did not have the traumatic event when the lesion was repaired. In the older patient population (age over 45 years), minimum intervention (debridement, biceps tenodesis/tenotomy) to the type II SLAP lesion results in excellent patient satisfaction and outcomes

Evaluation of Three Amorphous Drug Delivery Technologies to Improve the Oral Absorption of Flubendazole

AbstractThis study investigates 3 amorphous technologies to improve the dissolution rate and oral bioavailability of flubendazole (FLU). The selected approaches are (1) a standard spray-dried dispersion with hydroxypropylmethylcellulose (HPMC) E5 or polyvinylpyrrolidone-vinyl acetate 64, both with Vitamin E d-α-tocopheryl polyethylene glycol succinate; (2) a modified process spray-dried dispersion (MPSDD) with either HPMC E3 or hydroxypropylmethylcellulose acetate succinate (HPMCAS-M); and (3) confining FLU in ordered mesoporous silica (OMS). The physicochemical stability and in vitro release of optimized formulations were evaluated following 2 weeks of open conditions at 25°C/60% relative humidity (RH) and 40°C/75% RH. All formulations remained amorphous at 25°C/60% RH. Only the MPSDD formulation containing HPMCAS-M and 3/7 (wt./wt.) FLU/OMS did not crystallize following 40°C/75% RH exposure. The OMS and MPSDD formulations contained the lowest and highest amount of hydrolyzed degradant, respectively. All formulations were dosed to rats at 20 mg/kg in suspension. One FLU/OMS formulation was also dosed as a capsule blend. Plasma concentration profiles were determined following a single dose. In vivo findings show that the OMS capsule and suspension resulted in the overall highest area under the curve and Cmax values, respectively. These results cross-evaluate various amorphous formulations and provide a link to enhanced biopharmaceutical performance

Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial.

BACKGROUND: Moderate vitamin B-12 deficiency is relatively common in older people. However, there is little robust evidence on the effect of vitamin B-12 supplementation on neurologic and cognitive outcomes in later life. OBJECTIVE: We investigated whether vitamin B-12 supplementation benefits neurologic and cognitive function in moderately vitamin B-12-deficient older people. DESIGN: We conducted a double-blind, randomized, placebo-controlled trial in 7 general practices in South East England, United Kingdom. Study participants were aged ≥75 y and had moderate vitamin B-12 deficiency (serum vitamin B-12 concentrations: 107-210 pmol/L) in the absence of anemia and received 1 mg crystalline vitamin B-12 or a matching placebo as a daily oral tablet for 12 mo. Peripheral motor and sensory nerve conduction, central motor conduction, a clinical neurologic examination, and cognitive function were assessed before and after treatment. RESULTS: A total of 201 participants were enrolled in the trial, and 191 subjects provided outcome data. Compared with baseline, allocation to vitamin B-12 was associated with a 177% increase in serum concentration of vitamin B-12 (641 compared with 231 pmol/L), a 331% increase in serum holotranscobalamin (240 compared with 56 pmol/L), and 17% lower serum homocysteine (14.2 compared with 17.1 μmol/L). In intention-to-treat analysis of covariance models, with adjustment for baseline neurologic function, there was no evidence of an effect of supplementation on the primary outcome of the posterior tibial compound muscle action potential amplitude at 12 mo (mean difference: -0.2 mV; 95% CI: -0.8, 0.3 mV). There was also no evidence of an effect on any secondary peripheral nerve or central motor function outcome, or on cognitive function or clinical examination. CONCLUSION: Results of the trial do not support the hypothesis that the correction of moderate vitamin B-12 deficiency, in the absence of anemia and of neurologic and cognitive signs or symptoms, has beneficial effects on neurologic or cognitive function in later life. This trial was registered at www.isrctn.com as ISRCTN54195799

Study protocol for a type III hybrid effectiveness-implementation trial of strategies to implement firearm safety promotion as a universal suicide prevention strategy in pediatric primary care

BACKGROUND: Insights from behavioral economics, or how individuals\u27 decisions and behaviors are shaped by finite cognitive resources (e.g., time, attention) and mental heuristics, have been underutilized in efforts to increase the use of evidence-based practices in implementation science. Using the example of firearm safety promotion in pediatric primary care, which addresses an evidence-to-practice gap in universal suicide prevention, we aim to determine: is a less costly and more scalable behavioral economic-informed implementation strategy (i.e., Nudge ) powerful enough to change clinician behavior or is a more intensive and expensive facilitation strategy needed to overcome implementation barriers? METHODS: The Adolescent and child Suicide Prevention in Routine clinical Encounters (ASPIRE) hybrid type III effectiveness-implementation trial uses a longitudinal cluster randomized design. We will test the comparative effectiveness of two implementation strategies to support clinicians\u27 use of an evidence-based firearm safety practice, S.A.F.E. Firearm, in 32 pediatric practices across two health systems. All pediatric practices in the two health systems will receive S.A.F.E. Firearm materials, including training and cable locks. Half of the practices (k = 16) will be randomized to receive Nudge; the other half (k = 16) will be randomized to receive Nudge plus 1 year of facilitation to target additional practice and clinician implementation barriers (Nudge+). The primary implementation outcome is parent-reported clinician fidelity to the S.A.F.E Firearm program. Secondary implementation outcomes include reach and cost. To understand how the implementation strategies work, the primary mechanism to be tested is practice adaptive reserve, a self-report practice-level measure that includes relationship infrastructure, facilitative leadership, sense-making, teamwork, work environment, and culture of learning. DISCUSSION: The ASPIRE trial will integrate implementation science and behavioral economic approaches to advance our understanding of methods for implementing evidence-based firearm safety promotion practices in pediatric primary care. The study answers a question at the heart of many practice change efforts: which strategies are sufficient to support change, and why? Results of the trial will offer valuable insights into how best to implement evidence-based practices that address sensitive health matters in pediatric primary care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04844021 . Registered 14 April 2021

Scoring method of a Situational Judgment Test:influence on internal consistency reliability, adverse impact and correlation with personality?

textabstractSituational Judgment Tests (SJTs) are increasingly used for medical school selection. Scoring an SJT is more complicated than scoring a knowledge test, because there are no objectively correct answers. The scoring method of an SJT may influence the construct and concurrent validity and the adverse impact with respect to non-traditional students. Previous research has compared only a small number of scoring methods and has not studied the effect of scoring method on internal consistency reliability. This study compared 28 different scoring methods for a rating SJT on internal consistency reliability, adverse impact and correlation with personality. The scoring methods varied on four aspects: the way of controlling for systematic error, and the type of reference group, distance and central tendency statistic. All scoring methods were applied to a previously validated integrity-based SJT, administered to 931 medical school applicants. Internal consistency reliability varied between .33 and .73, which is likely explained by the dependence of coefficient alpha on the total score variance. All scoring methods led to significantly higher scores for the ethnic majority than for the non-Western minorities, with effect sizes ranging from 0.48 to 0.66. Eighteen scoring methods showed a significant small positive correlation with agreeableness. Four scoring methods showed a significant small positive correlation with conscientiousness. The way of controlling for systematic error was the most influential scoring method aspect. These results suggest that the increased use of SJTs for selection into medical school must be accompanied by a thorough examination of the scoring method to be used

Hair Cortisol in Twins : Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

A. Palotie on työryhmän jäsen.Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.Peer reviewe

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe