Researching Students with Disabilities: The Importance of Critical Perspectives

In this chapter, the authors critically review the current state of quantitative research on college students with disabilities and examine the exclusion of this marginalized population from much of our research. They propose ways to conduct research that more fully accounts for this diverse and important college population. The authors argue that critical quantitative research will produce more thorough knowledge and, in turn, policies and practices that will lead to more equitable college outcomes for students with disabilities

Establishing the Socio-Economic Impact of Degenerative Cervical Myelopathy Is Fundamental to Improving Outcomes [AO Spine RECODE-DCM Research Priority Number 8]

Study design: Literature Review (Narrative). Objective: To contextualize AO Spine RECODE-DCM research priority number 5: What is the socio-economic impact of DCM? (The financial impact of living with DCM to the individual, their supporters, and society as a whole). Methods: In this review, we introduce the methodology of health-economic investigation, including potential techniques and approaches. We summarize the current health-economic evidence within DCM, so far focused on surgical treatment. We also cover the first national estimate, in partnership with Myelopathy.org from the United Kingdom, of the cost of DCM to society. We then demonstrate the significance of this question to advancing care and outcomes in the field. Results: DCM is a common and often disabling condition, with a significant lack of recognition. While evidence demonstrates the cost-effectives of surgery, even among higher income countries, health inequalities exist. Further the prevalent residual disability in myelopathy, despite treatment affects both the individual and society as a whole. A report from the United Kingdom provides the first cost-estimate to their society; an annual cost of ∼£681.6 million per year, but this is likely a significant underestimate. Conclusion: A clear quantification of the impact of DCM is needed to raise the profile of a common and disabling condition. Current evidence suggests this is likely to be globally substantial

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

Improving Awareness Could Transform Outcomes in Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 1]

Study design: Literature Review (Narrative). Objective: To introduce the number one research priority for Degenerative Cervical Myelopathy (DCM): Raising Awareness. Methods: Raising awareness has been recognized by AO Spine RECODE-DCM as the number one research priority. This article reviews the evidence that awareness is low, the potential drivers, and why this must be addressed. Case studies of success from other diseases are also reviewed, drawing potential parallels and opportunities for DCM. Results: DCM may affect as many as 1 in 50 adults, yet few will receive a diagnosis and those that do will wait many years for it. This leads to poorer outcomes from surgery and greater disability. DCM is rarely featured in healthcare professional training programs and has received relatively little research funding (\u3c2% of Amyotrophic Lateral Sclerosis or Multiple Sclerosis over the last 25 years). The transformation of stroke and acute coronary syndrome services, from a position of best supportive care with occasional surgery over 50 years ago, to avoidable disability today, represents transferable examples of success and potential opportunities for DCM. Central to this is raising awareness. Conclusion: Despite the devastating burden on the patient, recognition across research, clinical practice, and healthcare policy are limited. DCM represents a significant unmet need that must become an international public health priority

Les lycaons et leurs ascendants fossiles : apport de l’expérimentation pour l’identification de leur signature taphonomique

International audienc

A dynamic study of the anterior cruciate ligament of the knee using an open MRI.

Place: GermanyRecent anatomical and radiological studies of the anterior cruciate ligament (ACL) suggest the ACL length and orientation change during knee flexion, and an open MRI sequencing during knee flexion enables a dynamic ACL analysis. This study's goal is to describe a normal ACL using a 1T open MRI and, in particular, variations in length and insertion angles at different degrees of flexion. Twenty-one volunteers with clinically healthy knees received a dynamic MRI with their knees in hyperextension, neutral position, and flexed at 45° and 90° angles. For each position, two radiologists measured the ACL lengths and angles of the proximal insertion between the ACL's anterior edge and the roof of the inter-condylar notch. Additionally, we measured the ACL's and the tibial plateau's distal angle insertion between their anterior edges and then compared these with the nonparametric Wilcoxon test. The ACL had a significant extension between the 90° flexion and all other positions (hyperextension: 31.75 ± 2.5 mm, neutral position: 32.5 ± 2.6 mm, 45°: 35.6 ± 1.6 mm, 90°: 35.6 ± 1.6 mm). There was also a significant increase of the angle insertion between the proximal 90° flexion and all other positions, as well as between hyperextension and bending to 45° (hyperextension: 2.45° ± 3.7°, neutral: 13.4° ± 9.7°, 45°: 33 25 ± 9.3, 90: 51.85° ± 9.3°). Additionally, there is a significant increase in the distal angle insertion for all positions (hyperextension: 133.2° ± 5.4°, neutral position: 134.95° ± 4.4°, 45°: 138.35° ± 5.9°, 90°: 149.15° ± 8.6°). Our study is the first to exhibit that a dynamic MRI has a significant ACL extension in vivo during bending. This concept opens the way for further studies to improve the diagnosis of traumatic ACL injuries using a dynamic MRI

Machine Learning Methods Improve Prognostication, Identify Clinically Distinct Phenotypes, and Detect Heterogeneity in Response to Therapy in a Large Cohort of Heart Failure Patients

Background-Whereas heart failure (HF) is a complex clinical syndrome, conventional approaches to its management have treated it as a singular disease, leading to inadequate patient care and inefficient clinical trials. We hypothesized that applying advanced analytics to a large cohort of HF patients would improve prognostication of outcomes, identify distinct patient phenotypes, and detect heterogeneity in treatment response. Methods and Results-The Swedish Heart Failure Registry is a nationwide registry collecting detailed demographic, clinical, laboratory, and medication data and linked to databases with outcome information. We applied random forest modeling to identify predictors of 1-year survival. Cluster analysis was performed and validated using serial bootstrapping. Association between clusters and survival was assessed with Cox proportional hazards modeling and interaction testing was performed to assess for heterogeneity in response to HF pharmacotherapy across propensity-matched clusters. Our study included 44 886 HF patients enrolled in the Swedish Heart Failure Registry between 2000 and 2012. Random forest modeling demonstrated excellent calibration and discrimination for survival (C-statistic=0.83) whereas left ventricular ejection fraction did not (C-statistic=0.52): there were no meaningful differences per strata of left ventricular ejection fraction (1-year survival: 80%, 81%, 83%, and 84%). Cluster analysis using the 8 highest predictive variables identified 4 clinically relevant subgroups of HF with marked differences in 1-year survival. There were significant interactions between propensity-matched clusters (across age, sex, and left ventricular ejection fraction and the following medications: diuretics, angiotensin-converting enzyme inhibitors, )i-blockers, and nitrates, Pamp;lt;0.001, all). Conclusions-Machine learning algorithms accurately predicted outcomes in a large data set of HF patients. Cluster analysis identified 4 distinct phenotypes that differed significantly in outcomes and in response to therapeutics. Use of these novel analytic approaches has the potential to enhance effectiveness of current therapies and transform future HF clinical trials.Funding Agencies|Swedish Federal Government; Swedish Research Council; Swedish Heart-Lung Foundation; Stockholm County Council</p

Correlation between serum gastrin and cellular proliferation in Barrett’s esophagus

Background: Patients with Barrett’s esophagus (BE) are commonly treated with proton-pump inhibitors (PPIs) to minimize the exposure of esophageal mucosa to stomach acid. However, the use of these medications can lead to significant hypergastrinemia in a subset of patients, which is concerning due to the known tumorigenic and proliferative effects of gastrin. The present pilot study aims to investigate a potential correlation between serum gastrin and cellular proliferation in BE