Continuous monitoring of mining induced strain in a road pavement using fiber Bragg grating sensors

Abstrakt Få samhällsproblem har under de senaste åren mött så allmän uppmärksamhet som ungdomsbrottsligheten. Den polisanmälda ungdomsbrottsligheten har i stort sett följt brottslighetens utvecklingskurva avseende antal begångna brott, denna kurva visar en tydlig ökning sedan efterkrigstiden. Detta är en komparativ uppsats som är inriktad på ungdomsbrottsligheten i två av Malmö stadsdelar där vi undersöker antalet polisanmälda ungdomar till socialtjänsten mellan åren 2007-2009. Vi har studerat vilka brott ungdomarna var anmälda, analyserat brottstrender och i den mån det var möjligt granskat hur könsfördelningen har sett ut. Vi har undersökt vilka insatser som tillämpas från socialtjänstens håll för att motverka ungdomsbrottslighet samt förhindra fortsatt brottslighet hos redan polisanmälda ungdomar samt granska hur socialsekreterare vid våra undersökningsverksamheter upplever och uppfattar ungdomsbrottsligheten. Våra resultat har delvis ställts i relation till hur ungdomsbrottsligheten enligt tidigare forskning och redan befintlig statistik ser ut i Sverige. Vi har i uppsatsen använt oss av kvalitativ och kvantitativ datainsamlingsmetod samt ställt analysavsnitt och diskussionsavsnitt i relation till tidigare forskning och den av Travis Hirschis konstruerade teorin om sociala band. Studiens resultat visar bland annat att antalet polisanmälningar till socialtjänsterna har ökat, att killar begår fler brott än tjejer, att brottstyperna skiljer sig åt beroende på kön samt att ett mindre antal ungdomar ansvarar för en stor del av socialtjänsternas inkomna polisanmälningar

An Extended Targeted Copy Number Variation Detection Array Including 187 Genes for the Diagnostics of Neuromuscular Disorders

Background: Our previous array, the Comparative Genomic Hybridisation design (CGH-array) for nemaline myopathy (NM), named the NM-CGH array, revealed pathogenic copy number variation (CNV) in the genes for nebulin (NEB) and tropomyosin 3 (TPM3), as well as recurrent CNVs in the segmental duplication (SD), i.e. triplicate, region of NEB (TRI, exons 82-89, 90-97, 98-105). In the light of this knowledge, we have designed and validated an extended CGH array, which includes a selection of 187 genes known to cause neuromuscular disorders (NMDs). Objective: Our aim was to develop a reliable method for CNV detection in genes related to neuromuscular disorders for routine mutation detection and analysis, as a much-needed complement to sequencing methods. Methods: We have developed a novel custom-made 4×180 k CGH array for the diagnostics of NMDs. It includes the same tiled ultra-high density coverage of the 12 known or putative NM genes as our 8×60 k NM-CGH-array but also comprises a selection of 175 additional genes associated with NMDs, including titin (TTN), at a high to very high coverage. The genes were divided into three coverage groups according to known and potential pathogenicity in neuromuscular disorders. Results: The array detected known and putative CNVs in all three gene coverage groups, including the repetitive regions of NEB and TTN. Conclusions: The targeted neuromuscular disorder 4×180 k array-CGH (NMD-CGH-array v1.0) design allows CNV detection for a broader spectrum of neuromuscular disorders at a high resolution. © 2018 - IOS Press and the authors. All rights reserved.Peer reviewe

Elevated plasma levels of cardiac troponin-I predict left ventricular systolic dysfunction in patients with myotonic dystrophy type 1:A multicentre cohort follow-up study

Objective: High sensitivity plasma cardiac troponin-I (cTnI) is emerging as a strong predictor of cardiac events in a variety of settings. We have explored its utility in patients with myotonic dystrophy type 1 (DM1). Methods: 117 patients with DM1 were recruited from routine outpatient clinics across three health boards. A single measurement of cTnI was made using the ARCHITECT STAT Troponin I assay. Demographic, ECG, echocardiographic and other clinical data were obtained from electronic medical records. Follow up was for a mean of 23 months. Results: Fifty five females and 62 males (mean age 47.7 years) were included. Complete data were available for ECG in 107, echocardiography in 53. Muscle Impairment Rating Scale score was recorded for all patients. A highly significant excess (p = 0.0007) of DM1 patients presented with cTnI levels greater than the 99th centile of the range usually observed in the general population (9 patients; 7.6%). Three patients with elevated troponin were found to have left ventricular systolic dysfunction (LVSD), compared with four of those with normal range cTnI (33.3% versus 3.7%; p = 0.001). Sixty two patients had a cTnI level < 5ng/L, of whom only one had documented evidence of LVSD. Elevated cTnI was not predictive of severe conduction abnormalities on ECG, or presence of a cardiac device, nor did cTnI level correlate with muscle strength expressed by Muscle Impairment Rating Scale score. Conclusions: Plasma cTnI is highly elevated in some ambulatory patients with DM1 and shows promise as a tool to aid cardiac risk stratification, possibly by detecting myocardial involvement. Further studies with larger patient numbers are warranted to assess its utility in this setting

Dominantly inherited distal nemaline/cap myopathy caused by a large deletion in the nebulin gene

We report the first family with a dominantly inherited mutation of the nebulin gene (NEB). This 100kb in-frame deletion encompasses NEB exons 14-89, causing distal nemaline/cap myopathy in a three-generation family. It is the largest deletion characterized in NEB hitherto. The mutated allele was shown to be expressed at the mRNA level and furthermore, for the first time, a deletion was shown to cause the production of a smaller mutant nebulin protein. Thus, we suggest that this novel mutant nebulin protein has a dominant-negative effect, explaining the first documented dominant inheritance of nebulin-caused myopathy. The index patient, a young man, was more severely affected than his mother and grandmother. His first symptom was foot drop at the age of three, followed by distal muscle atrophy, slight hypomimia, high-arched palate, and weakness of the neck and elbow flexors, hands, tibialis anterior and toe extensors. Muscle biopsies showed myopathic features with type 1 fibre predominance in the index patient and nemaline bodies and cap-like structures in biopsies from his mother and grandmother. The muscle biopsy findings constitute a further example of nemaline bodies and cap-like structures being part of the same spectrum of pathological changes. (C) 2019 Elsevier B.V. All rights reserved.Peer reviewe

Delay in diagnosis of muscle disorders depends on the subspecialty of the initially consulted physician

<p>Abstract</p> <p>Background</p> <p>New therapeutic strategies in muscular dystrophies will make a difference in prognosis only if they are begun early in the course of the disease. Therefore, we investigated factors that influence the time to diagnosis in muscle dystrophy patients.</p> <p>Methods</p> <p>A sample of 101 patients (mean age 49 years; range 19-80; 44% women) with diagnosed muscle dystrophies from neurological practices and the neuromuscular specialty clinic in Berlin, Germany, was invited to participate. Time from first consultation to diagnosis, subspecialty of physician, and sociodemographic data were assessed with self-report questionnaires. The association between time to diagnosis and potential predictors (subspecialty of initially consulted physician, diagnoses, gender, and age at onset) was modeled with linear regression analysis.</p> <p>Results</p> <p>The mean time span between first health-care contact and diagnosis was 4.3 years (median 1). The diagnostic delay was significantly longer if patients were initially seen by a non-neurological specialist compared to a general practitioner (5.2 vs. 3.5 years, p = 0.047). Other factors that were independently associated with diagnostic delay were female gender and inherited muscle disease.</p> <p>Conclusion</p> <p>Action to improve clinical awareness of muscle diseases in non-neurological specialists is needed.</p

Loss of MICOS complex integrity and mitochondrial damage, but not TDP-43 mitochondrial localisation, are likely associated with severity of CHCHD10-related diseases

Following the involvement of CHCHD10 in FrontoTemporal-Dementia-Amyotrophic Lateral Sclerosis (FTD-ALS) clinical spectrum, a founder mutation (p.Gly66Val) in the same gene was identified in Finnish families with late-onset spinal motor neuronopathy (SMAJ). SMAJ is a slowly progressive form of spinal muscular atrophy with a life expectancy within normal range. In order to understand why the p.Ser59Leu mutation, responsible for severe FTD-ALS, and the p.Gly66Val mutation could lead to different levels of severity, we compared their effects in patient cells. Unlike affected individuals bearing the p.Ser59Leu mutation, patients presenting with SMAJ phenotype have neither mitochondrial myopathy nor mtDNA instability. The expression of CHCHD10S59L mutant allele leads to disassembly of mitochondrial contact site and cristae organizing system (MICOS) with mitochondrial dysfunction and loss of cristae in patient fibroblasts. We also show that G66V fibroblasts do not display the loss of MICOS complex integrity and mitochondrial damage found in S59L cells. However, S59L and G66V fibroblasts show comparable accumulation of phosphorylated mitochondrial TDP-43 suggesting that the severity of phenotype and mitochondrial damage do not depend on mitochondrial TDP-43 localization. The expression of the CHCHD10G66V allele is responsible for mitochondrial network fragmentation and decreased sensitivity towards apoptotic stimuli, but with a less severe effect than that found in cells expressing the CHCHD10S59L allele. Taken together, our data show that cellular phenotypes associated with p.Ser59Leu and p.Gly66Val mutations in CHCHD10 are different; loss of MICOS complex integrity and mitochondrial dysfunction, but not TDP-43 mitochondrial localization, being likely essential to develop a severe motor neuron disease

Distinct muscle imaging patterns in myofibrillar myopathies

Objective: To compare muscle imaging findings in different subtypes of myofibrillar myopathies (MFM) in order to identify characteristic patterns of muscle alterations that may be helpful to separate these genetic heterogeneous muscular disorders. Methods: Muscle imaging and clinical findings of 46 patients with MFM were evaluated (19 desminopathy, 12 myotilinopathy, 11 filaminopathy, 1 alpha B-crystallinopathy, and 3 ZASPopathy). The data were collected retrospectively in 43 patients and prospectively in 3 patients. Results: In patients with desminopathy, the semitendinosus was at least equally affected as the biceps femoris, and the peroneal muscles were never less involved than the tibialis anterior (sensitivity of these imaging criteria to detect desminopathy in our cohort 100%, specificity 95%). In most of the patients with myotilinopathy, the adductor magnus showed more alterations than the gracilis muscle, and the sartorius was at least equally affected as the semitendinosus (sensitivity 90%, specificity 93%). In filaminopathy, the biceps femoris and semitendinosus were at least equally affected as the sartorius muscle, and the medial gastrocnemius was more affected than the lateral gastrocnemius. The semimembranosus mostly showed more alterations than the adductor magnus (sensitivity 88%, specificity 96%). Early adult onset and cardiac involvement was most often associated with desminopathy. In patients with filaminopathy, muscle weakness typically beginning in the 5th decade of life was mostly pronounced proximally, while late adult onset (> 50 years) with distal weakness was more often present in myotilinopathy. Conclusions: Muscle imaging in combination with clinical data may be helpful for separation of distinct myofibrillar myopathy subtypes and in scheduling of genetic analysis