Measures of Fine Motor Skills in People with Tremor Disorders: Appraisal and Interpretation

People with Parkinson’s disease, essential tremor, or other movement disorders involving tremor have changes in fine motor skills that are among the hallmarks of these diseases. Numerous measurement tools have been created and other methods devised to measure such changes in fine motor skills. Measurement tools may focus on specific features – e.g., motor skills or dexterity, slowness in movement execution associated with parkinsonian bradykinesia, or magnitude of tremor. Less obviously, some tools may be better suited than others for specific goals such as detecting subtle dysfunction early in disease, revealing aspects of brain function affected by disease, or tracking changes expected from treatment or disease progression. The purpose of this review is to describe and appraise selected measurement tools of fine motor skills appropriate for people with tremor disorders. In this context, we consider the tools’ content – i.e., what movement features they focus on. In addition, we consider how measurement tools of fine motor skills relate to measures of a person’s disease state or a person’s function. These considerations affect how one should select and interpret the results of these tools in laboratory and clinical contexts

Comorbid conditions explain the association between posttraumatic stress disorder and incident cardiovascular disease

Background Posttraumatic stress disorder ( PTSD ) is associated with risk of cardiovascular disease ( CVD ). Biopsychosocial factors associated with PTSD likely account for some or all of this association. We determined whether 1, or a combination of comorbid conditions explained the association between PTSD and incident CVD . Methods and Results Eligible patients used 1 of 5 Veterans Health Affairs medical centers distributed across the United States. Data were obtained from electronic health records. At index date, 2519 Veterans Health Affairs ( VA ) patients, 30 to 70 years of age, had PTSD diagnoses and 1659 did not. Patients had no CVD diagnoses for 12 months before index date. Patients could enter the cohort between 2008 and 2012 with follow-up until 2015. Age-adjusted Cox proportional hazard models were computed before and after adjusting for comorbidities. Patients were middle aged (mean=50.1 years, SD ±11.0), mostly male (87.0%), and 60% were white. The age-adjusted association between PTSD and incident CVD was significant (hazard ratio=1.41; 95% CI : 1.21-1.63). After adjustment for metabolic conditions, the association between PTSD and incident CVD was attenuated but remained significant (hazard ratio=1.23; 95% CI : 1.06-1.44). After additional adjustment for smoking, sleep disorder, substance use disorder, anxiety disorders, and depression, PTSD was not associated with incident CVD (hazard ratio=0.96; 95% CI : 0.81-1.15). Conclusions PTSD is not an independent risk factor for CVD . Physical and psychiatric conditions and smoking that co-occur with PTSD explain why this patient population has an increased risk of CVD . Careful monitoring may limit exposure to CVD risk factors and subsequent incident CVD

Mapping Evidence From the Literature About the Experience of Internationally Educated Health Professionals to Canadian Professional Competency Profiles of Physiotherapists, Occupational Therapists, Physicians, and Pharmacists.

Abstract Purpose: To review experiences of internationally educated healthcare professionals (physiotherapists, occupational therapists, physicians and pharmacists) in their new country and to map these experiences using a competency framework. Method: Database (Medline, EMBASE, CINAHL, and PsycINFO ) were systematically searched to include articles published between 2000 and 2017 and described the experiences of internationally educated healthcare professionals (IEHPs) in physiotherapists, occupational therapists, physicians and pharmacist in attaining registration in new country. The data were synthesised using conventional content analysis. Emerging themes were mapped across a competency framework based on the profiles of the selected professions. Result: Thirteen articles were included; most were conducted in Canada and among internationally educated medical doctors. Themes were mapped to all the roles in the professional competency profiles except the Health Advocate role. Communicator role was the most frequently discussed; internationally educated healthcare professionals often needed to improve in culture-specific communication including verbal and non-verbal cues during assessment, documentation and treatment of clients. A pictorial representation was created for describing internationally educated healthcare professionals’ deficiencies in roles/ competencies for professional practice. In this representation, cultural-language and confidence deficits contribute to the deficiencies seen in roles and competencies among internationally educated healthcare professionals in their new country. Conclusion: Internationally educated healthcare professionals’ ability to fulfill the explicit roles in the competency profiles may depend largely on having good cultural-language competence as well as confidence. Exposing the internationally educated healthcare professionals to local practice is one of the strategies for cultural-language and confidence enhancement, consistent with findings reported in the nursing profession

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

“Gleaning a lot from the history and physical exam,” and “reasonably confident without imaging”:a qualitative study of primary care clinicians' management of patients with low back pain

Background: Routine seeking of imaging for patients with low back pain is not concordant with the evidence-based recommendation that imaging is rarely of diagnostic value. Inappropriate imaging is a waste of resources and can lead to undesirable downstream effects for individuals and health systems. To develop effective strategies to reduce unwarranted referrals for imaging in primary care, we must understand the drivers for, and barriers to, guideline-adherent practice. We explored clinicians’ views to identify the dominant influences on clinicians as they choose to pursue, or avoid, imaging for their patients with low back pain. Methods: We interviewed a purposeful sample of 47 primary care clinicians (14 physiotherapists, 18 chiropractors, 15 physicians) throughout Ontario, Canada, with a guide based on the Theoretical Domains Framework (TDF). We investigated clinicians’ views about their use of imaging in the management of low back pain. Interviews were recorded and transcribed verbatim. We analysed transcripts, then identified themes within TDF domains. Results: Most clinicians reported that, for most clinical encounters, they adhered to guideline recommendations about imaging. Many clinicians across disciplines expressed the following themes: (1) imaging may result in an incidental finding or otherwise cause harm to patients, and drive up health system costs (TDF domain Beliefs about consequences); (2) clinicians were confident in their abilities to diagnose, to explain to patients the rationale for not recommending imaging, and to respond to their needs (domains Beliefs about capabilities; Skills). Many clinicians identified that patients occasionally want the validation that imaging provides (domain Social influences). Some clinicians described the value of imaging to corroborate a diagnosis (domain Beliefs about consequences). Conclusions: This study is the first to examine influences on imaging behaviours of a large interprofessional sample of primary care clinicians in Canada. Even among knowledgeable, skilled, confident clinicians who reported mostly adhering to guideline recommendations, there are potential influences on deviating from guideline-adherent care.</p