The diagnostic value of the stump impingement reflex sign for determining anterior cruciate ligament stump impingement as a cause of knee locking

BACKGROUND: The stump impingement reflex is a subtle bounce to the knee thought to be caused by hamstring contraction when the knee is brought into extension and the torn ACL stump impinges between the distal femur and the tibial plateau. We have studied the diagnostic value of this sign. FINDINGS: From Feb 2008-Feb 2009, we audited 30 patients who underwent urgent arthroscopy for acutely locked knees. The presence of the stump impingement reflex prior to surgery was compared with the intra-operative findings. The diagnostic values of the stump impingement sign were found to be: Sensitivity 58%, Specificity 81%, Positive predictive value 70%, Negative predictive value 72% and Accuracy 71%. CONCLUSIONS: We believe that the stump impingement reflex is a specific sign for ACL stump impingement as a cause of knee locking. We recommend close inspection for this sign when examining locked knees

Predictive significance of the six-minute walk distance for long-term survival in chronic hypercapnic respiratory failure

Background: The 6-min walk distance ( 6-MWD) is a global marker of functional capacity and prognosis in chronic obstructive pulmonary disease ( COPD), but less explored in other chronic respiratory diseases. Objective: To study the role of 6-MWD in chronic hypercapnic respiratory failure ( CHRF). Methods: In 424 stable patients with CHRF and non-invasive ventilation ( NIV) comprising COPD ( n = 197), restrictive diseases ( RD; n = 112) and obesity-hypoventilation- syndrome ( OHS; n = 115), the prognostic value of 6-MWD for long- term survival was assessed in relation to that of body mass index (BMI), lung function, respiratory muscle function and laboratory parameters. Results: 6-MWD was reduced in patients with COPD ( median 280 m; quartiles 204/350 m) and RD ( 290 m; 204/362 m) compared to OHS ( 360 m; 275/440 m; p <0.001 each). Overall mortality during 24.9 (13.1/40.5) months was 22.9%. In the 424 patients with CHRF, 6-MWD independently predicted mortality in addition to BMI, leukocytes and forced expiratory volume in 1 s ( p <0.05 each). In COPD, 6-MWD was strongly associated with mortality using the median {[} p <0.001, hazard ratio ( HR) = 3.75, 95% confidence interval (CI): 2.24-6.38] or quartiles as cutoff levels. In contrast, 6-MWD was only significantly associated with impaired survival in RD patients when it was reduced to 204 m or less (1st quartile; p = 0.003, HR = 3.31, 95% CI: 1.73-14.10), while in OHS 6-MWD had not any prognostic value. Conclusions: In patients with CHRF and NIV, 6-MWD was predictive for long- term survival particularly in COPD. In RD only severely reduced 6-MWD predicted mortality, while in OHS 6-MWD was relatively high and had no prognostic value. These results support a disease-specific use of 6-MWD in the routine assessment of patients with CHRF. Copyright (C) 2007 S. Karger AG, Basel

Growing partnership communities: What experiences of an international institute suggest about developing student-staff partnership in higher education

This article explores the perceptions of participants following the first International Summer Institute (SI) on students as partners in higher education, a four-day professional development experience designed to foster student-staff partnerships. Approximately 9 months after the Institute, 10 participants were interviewed to understand their perceptions of student-staff partnership, and what role the SI played in supporting partnership working. We discuss the key themes that emerged from our interviews, and analyse these participant responses in comparison to responses collected during the 2016 SI. In evaluating our data, we consider the general efficacy of the SI and offer ideas for academic developers interested in supporting partnership work more generally

Increased CNV-Region Deletions in Mild Cognitive Impairment (MCI) and Alzheimer\u27s Disease (AD) Subjects in the ADNI Sample

We investigated the genome-wide distribution of CNVs in the Alzheimer\u27s disease (AD) Neuroimaging Initia- tive (ADNI) sample (146 with AD, 313 with Mild Cognitive Impairment (MCI), and 181 controls). Comparison of single CNVs between cases (MCI and AD) and controls shows overrepresentation of large hetero- zygous deletions in cases (p-value b 0.0001). The analysis of CNV-Regions identifies 44 copy number variable loci of heterozygous deletions, with more CNV-Regions among affected than controls (p = 0.005). Seven of the 44 CNV-Regions are nominally significant for association with cognitive impairment. We validated and con- firmed our main findings with genome re-sequencing of selected patients and controls. The functional pathway analysis of the genes putatively affected by deletions of CNV-Regions reveals enrichment of genes implicated in axonal guidance, cell–cell adhesion, neuronal morphogenesis and differentiation. Our findings support the role of CNVs in AD, and suggest an association between large deletions and the development of cognitive impairment

Dopaminergic modulation of cortical motor network lateralization

Introduction Unilateral movements are primarily processed in contralateral cortical and subcortical areas and additionally in ipsilateral cerebellum, leading to an asymmetric pattern of neural activation. Decrease of lateralization is characteristic of aging (Naccarato et al., 2006; Wu et al., 2005), and disease, for example, in unilateral brain lesions or stroke (Carr et al., 1993; Rehme et al., 2011) and Parkinson's disease (PD; Wu et al., 2015). The explanation for imbalanced lateralization in drug-naive PD is an adaptive compensation, compatible with the finding that PD-associated deficient input from cortico-subcortical circuits is compensated by reduced cortical inhibition and increased cortical facilitation (Blesa et al., 2017). Here, we investigated the effect of dopamine depletion and substitution on cortical motor lateralization, with the hypothesis that lateralization decreases in advanced PD and that administration of levodopa, at least to a certain extent, reinstates lateralization. Methods We used fMRI to study motor activation in advanced PD patients and in healthy controls (HC) during unilateral upper and lower limb movements. Ten right-handed, left side symptom-dominant PD patients were tested in pseudo-randomized order after intake of their usual dopaminergic medication – 'ON' state – and after withdrawal of medication – 'OFF' state. Eighteen right-handed age-matched HC participated in a single session. We quantified activation lateralization using the average laterality index (AveLI; Matsuo et al., 2012) in three cortical motor regions of interest (ROIs): primary motor cortex (M1), supplementary motor area (SMA) and premotor cortex (PMC), during the four movement conditions. We compared AveLI between group pairs (PD OFF vs. HC, PD ON vs. HC, PD OFF vs. PD ON) within each ROI and movement condition. We estimated the effective connectivity between ROIs using bilinear dynamic causal modeling (DCM; Friston et al., 2003) and developed a measure to quantify the lateralization of the resulting connectivity networks to compare between groups. By constructing a group level parametric empirical Bayes (PEB) model (Friston et al., 2016) over all the subjects and conducting a search over nested models, we compared DCM parameter estimates between groups, thus providing the potential link between changes in motor lateralization and connectivity. Results In line with our predictions, motor activation lateralization as estimated with the AveLI showed a trend towards decrease in the PD OFF group compared to HC, in all three ROIs during left hand movement and in M1 during left foot movement (Fig. 1). Between-group differences were observed solely in conditions corresponding to movement of the more affected body side. Contrary to our hypothesis, dopamine substitution did not reinstate lateralization – in fact, AveLI in the PD ON group closely resembled that of the PD OFF group. Connectivity lateralization of input-specific modulation (DCM.B) networks was significantly lower in all conditions in the PD group as compared to HC. While on the body side more affected by PD, differences were found for both PD OFF and PD ON, input-specific modulation related to the less affected side was more altered in PD ON. PEB analysis revealed qualitatively more between-group differences in input-specific modulation on the more affected PD side and included many interhemispheric connections (Fig. 2). Conclusions Decreased lateralization is not only present in drug-naïve PD patients (Wu et al., 2015) but also in dopa-treated patients. Acute dopamine modulation does not alter lateralization. Decreased lateralization is evident in both fMRI activation amplitudes (as estimated with AveLI) and effective connectivity (as demonstrated through the DCM analysis)

Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL

Contains fulltext : 169719.pdf (publisher's version ) (Open Access)The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high-throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ next-generation sequencing (NGS) based on small amplicons. Building on existing publications and general guidance for the clinical use of NGS and learnings from germline testing, the following guidelines establish consensus standards for somatic diagnostic testing, specifically for identifying and reporting mutations in solid tumours. These guidelines cover the testing strategy, implementation of testing within clinical service, sample requirements, data analysis and reporting of results. In conjunction with appropriate staff training and international standards for laboratory testing, these consensus standards for the use of NGS in molecular pathology of solid tumours will assist laboratories in implementing NGS in clinical services

Levels: Descriptive, Explanatory, and Ontological

Scientists and philosophers frequently speak about levels of description, levels of explanation, and ontological levels. In this paper, I propose a unified framework for modelling levels. I give a general definition of a system of levels and show that it can accommodate descriptive, explanatory, and ontological notions of levels. I further illustrate the usefulness of this framework by applying it to some salient philosophical questions: (1) Is there a linear hierarchy of levels, with a fundamental level at the bottom? And what does the answer to this question imply for physicalism, the thesis that everything supervenes on the physical? (2) Are there emergent properties? (3) Are higher-level descriptions reducible to lower-level ones? (4) Can the relationship between normative and non-normative domains be viewed as one involving levels? Although I use the terminology of “levels”, the proposed framework can also represent “scales”, “domains”, or “subject matters”, where these are not linearly but only partially ordered by relations of supervenience or inclusion