The accuracy of diagnostic ultrasound imaging for musculoskeletal soft tissue pathology of the extremities: A comprehensive review of the literature

Musculoskeletal diagnostic ultrasound imaging (MSK-DUSI) has been growing outside the traditional radiology speciality. Increased use of this technology has been reported in several healthcare settings, however an apparent gap in the knowledge of the accuracy of this diagnostic technology indicated a review was warranted. We undertook a structured review of the literature to assess the accuracy of MSK-DUSI for the diagnosis of musculoskeletal soft tissue pathology of the extremities. An electronic search of the National Library of Medicine’s PubMed database (1972 to mid-2014) was conducted. All relevant systematic reviews of diagnostic studies, all diagnostic studies published after the date of the latest systematic reviews and relevant diagnostic studies outside the scope the systematic reviews that directly compared the accuracy of MSK-DUSI (the index test) to an appropriate reference standard for the target condition were included. A fundamental appraisal of the methodological quality of studies was completed. The individual sensitivity, specificity and likelihood ratio data were extracted and entered into diagnostic accuracy tables. A total of 207 individual studies were included. The results show that MSK-DUSI has acceptable diagnostic accuracy for a wide spectrum of musculoskeletal conditions of the extremities. However, there is a lack of high quality prospective experimental studies in this area and as such clinicians should interpret the results with some caution due to the potential for overestimation of diagnostic accuracy

Synthesis of gold micro- and nano-wires by infiltration and thermolysis

An approach for synthesizing micro- and nano-sized gold wires by infiltration and thermolysis is investigated. A porous ZrO2 ceramic preform with aligned pores obtained by unidirectional freezing and freeze-drying is employed as an infiltration template. The sintered porous ZrO2 preform is then infiltrated by a brushing gold solution. The thermolysis is conducted at 600 °C in air. Micro- and nano-sized gold wires are developed within the walls of the pores after thermolysis. The diameter of the gold wires ranges from several hundred nanometers to several microns

Experimental and Modelling Investigations of Air Exchange and Infection Transfer due to Hinged-Door Motion in Office and Hospital Settings

Occupants spend a significant amount of time indoors where temperature and air quality has an important impact on their comfort, health and work performance. Understanding the role of airflow exchange between spaces is crucial to describe the processes of mixing and transport of substances driven by air motion and therefore essential for evaluating indoor air quality. This work presents the results of field measurements and laboratory experiments designed to characterise door operation and to quantify its influence on air volumes exchanged between rooms due to door motion. The field study was conducted to identify typical total door cycle times in single person offices. The laboratory experiments were conducted in a scale model to investigate the exchange flow between two generic rooms. The model consisted of a water filled tank divided into two equal rooms, which were connected by a computer-controlled hinged door. Flow visualisations were used to describe flow patterns and concentration measurements of Rhodamine WT were performed to quantify exchange volumes. With hold open times of between 0s and 26.67s the total fluid volume exchanged was found to be between 67% and 98% of the total volume swept. Based on the exchange volume found in these experiments combined with the Wells-Riley equation the effect of ventilation rate on the probability of occupants in an adjacent room becoming infected was investigated. With ventilation rates for a medium air quality the risk of infection is low (<0.05). However, the probability of infection quickly rises with lower ventilation rates

Mechanistic target of rapamycin (MTOR) protein expression in the tumor and its microenvironment correlates with more aggressive pathology at cystectomy

Background: The mechanistic target of rapamycin (mTOR) has been implicated in driving tumor biology in multiple malignancies, including urothelial carcinoma (UC). We investigate how mTOR and phosphorylated mTOR (pmTOR) protein expression correlate with chemoresponsiveness in the tumor and its microenvironment at final pathologic staging after neoadjuvant chemotherapy (NAC). Methods: A single-institution retrospective analysis was performed on 62 patients with cT2–4Nany UC undergoing NAC followed by radical cystectomy. Diagnostic (transurethral resection specimens, TURBT) and postchemotherapy radical cystectomy specimens were evaluated for mTOR and pmTOR protein expression using immunohistochemistry of the tumor, peritumoral stroma, and normal surrounding stroma. Protein expression levels were compared between clinical and pathologic stage. Whole transcriptome analysis was performed to evaluate mRNA expression relative to mTOR pathway activation. Results: Baseline levels of mTOR and pmTOR within TURBT specimens were not associated with clinical stage and response to chemotherapy overall. Nonresponders with advanced pathologic stage at cystectomy (ypT2–4/ypTanyN+) had significantly elevated mTOR tumor staining (P = 0.006) and a sustained mTOR and pmTOR staining in the peritumoral and surrounding normal stroma (NS). Several genes relevant to mTOR activity were found to be up-regulated in the tumors of nonresponders. Remarkably, complete responders at cystectomy (ypT0) had significant decreases in both mTOR and pmTOR protein expression in the peritumoral and normal stroma (P = 0.01–0.03). Conclusions: Our results suggest that mTOR pathway activity is increased in tumor and sustained in its microenvironment in patients with adverse pathologic findings at cystectomy. These findings suggest the relevance of targeting this pathway in bladder cancer

A population of highly energetic transient events in the centres of active galaxies

Recent all-sky surveys have led to the discovery of new types of transients. These include stars disrupted by the central supermassive black hole, and supernovae that are 10–100 times more energetic than typical ones. However, the nature of even more energetic transients that apparently occur in the innermost regions of their host galaxies is hotly debated1,2,3. Here we report the discovery of the most energetic of these to date: PS1-10adi, with a total radiated energy of ~2.3 × 1052 erg. The slow evolution of its light curve and persistently narrow spectral lines over ∼ 3 yr are inconsistent with known types of recurring black hole variability. The observed properties imply powering by shock interaction between expanding material and large quantities of surrounding dense matter. Plausible sources of this expanding material are a star that has been tidally disrupted by the central black hole, or a supernova. Both could satisfy the energy budget. For the former, we would be forced to invoke a new and hitherto unseen variant of a tidally disrupted star, while a supernova origin relies principally on environmental effects resulting from its nuclear location. Remarkably, we also discover that PS1-10adi is not an isolated case. We therefore surmise that this new population of transients has previously been overlooked due to incorrect association with underlying central black hole activity

Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium

Aims Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown. Methods and resultsA total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8) met the diagnostic criteria for OH (systolic/diastolic BP drop <20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95 confidence interval: 0.90, 0.850.96; P=0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.750.95; P=0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.870.98; P=0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.021.24; P=0.02, rs198358: 1.10, 1.011.20; P=0.04, and rs5068: 1.22, 1.041.43; P=0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P=0.04). ConclusionThe overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components

Genetic overlap between diagnostic subtypes of ischemic stroke

Background and Purpose: Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Methods: Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. Results: High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10-4) and profile scores (rg=0.72; 95% confid

Associations of NINJ2 sequence variants with incident ischemic stroke in the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) consortium

Background: Stroke, the leading neurologic cause of death and disability, has a substantial genetic component. We previously conducted a genome-wide association study (GWAS) in four prospective studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and demonstrated that sequence variants near the NINJ2 gene are associated with incident ischemic stroke. Here, we sought to fine-map functional variants in the region and evaluate the contribution of rare variants to ischemic stroke risk. Methods and Results: We sequenced 196 kb around NINJ2 on chromosome 12p13 among 3,986 European ancestry participants, including 475 ischemic stroke cases, from the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, and Framingham Heart Study. Meta-analyses of single-variant tests for 425 common variants (minor allele frequency [MAF] ≥ 1%) confirmed the original GWAS results and identified an independent intronic variant, rs34166160 (MAF = 0.012), most significantly associated with incident ischemic stroke (HR = 1.80, p = 0.0003). Aggregating 278 putatively-functional variants with MAF≤ 1% using count statistics, we observed a nominally statistically significant association, with the burden of rare NINJ2 variants contributing to decreased ischemic stroke incidence (HR = 0.81; p = 0.026). Conclusion: Common and rare variants in the NINJ2 region were nominally associated with incident ischemic stroke among a subset of CHARGE participants. Allelic heterogeneity at this locus, caused by multiple rare, low frequency, and common variants with disparate effects on risk, may explain the difficulties in replicating the original GWAS results. Additional studies that take into account the complex allelic architecture at this locus are needed to confirm these findings

Best Practices and Joint Calling of the HumanExome BeadChip: The CHARGE Consortium

Genotyping arrays are a cost effective approach when typing previously-identified genetic polymorphisms in large numbers of samples. One limitation of genotyping arrays with rare variants (e.g., minor allele frequency [MAF] <0.01) is the difficulty that automated clustering algorithms have to accurately detect and assign genotype calls. Combining intensity data from large numbers of samples may increase the ability to accurately call the genotypes of rare variants. Approximately 62,000 ethnically diverse samples from eleve

Fast-timing measurements in neutron-rich odd-mass zirconium isotopes using LaBr3:Ce detectors coupled with Gammasphere

A fast-timing experiment was performed at the Argonne National Laboratory to measure the lifetimes of the lowest lying states of nuclei belonging to the deformed regions around mass number A 110 and A 150. These regions were populated via spontaneous fission of 252 Cf and the gamma radiation following the decay of excited states in the fission fragments was measured using 51 Gammasphere detectors coupled with 25 LaBr 3 :Ce detectors. A brief description of the acquisition system and some preliminary results from the fast-timing analysis of the fission fragment 100Zr are presented. The lifetime value of \u3c4 = 840(65) ps was found for the 2 + state in 100 Zr consistent within one standard deviation of the adopted value with 791 +26 -35 ps. This is associated with a quadrupole deformation parameter of 0.36(2) which is within one standard deviation of the literature value of 0.3556 +82 -57