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Cutaneous leiomyosarcoma (cLMS) is a rare soft tissue sarcoma where the genetic drivers implicated in carcinogenesis are not completely characterized despite extensive genomic profiling. The presentation of cLMS in Birt-Hogg-Dube (BHD) syndrome, which is caused by heterozygous pathogenic variants in FLCN, adds to our mechanistic understanding of the pathogenesis of cLMS and implicates FLCN loss. In this report, we demonstrate loss of heterozygosity (LOH) of FLCN in BHD cLMS, providing novel genetic evidence that a subset of cLMS may be driven by FLCN loss and that cLMS is an infrequent but recurrent element of the BHD phenotype.

We present a case of a 74-year-old man with marked photodamage who was ultimately diagnosed with telangiectasia macularis eruptiva perstans (TMEP) of the scalp. The diagnosis was made more difficult because of the clinical and histological similarity of this case with an early angiosarcoma. TMEP is a benign and indolent rare subtype of cutaneous mastocytosis presenting clinically with red-brown telangiectatic macules, usually symmetrically distributed over the trunk and extremities. Although most cases are limited to the skin, systemic involvement can occur, and this can be a potentially life-threatening disease. Although also rare, in contrast to TMEP, cutaneous angiosarcoma is a highly malignant vascular tumor with a poor prognosis. This case highlights the importance of including TMEP on the differential diagnosis where vascular lesions of the scalp are observed.

Piezoelectric energy conversion has received considerable attention for vibration-to-electric energy conversion over the past decade. A typical piezoelectric energy harvester is a unimorph or a bimorph cantilever located on a vibrating host structure. This paper presents a comparison between unimorph and bimorph cantilever beam having a number of segmented PMN-PT piezo-elements on the input and output power. The numerical simulation was carried out by applying the finite element analysis (FEA) using COMSOL multi-physics software in order to predict output voltage and power over a frequency range of 60–200 Hz for the first resonant frequencies. The simulation results show maximum output voltage and power harvested of 7.38 V and 135.73 μW, respectively, by the unimorph piezoelectric energy harvester at resonant frequency value of 84 Hz with electromechanical coupling factor (ke) of 77.29%. These results highlight that the highest value of the output electrical power can be obtained when the piezoelectric element is attached on the top of a clamped end of a cantilever piezoelectric beam. Moreover, in an unimorph or bimorph cantilever beam system, increasing the number of piezoelectric elements results in a higher resonant frequency shift and significantly decreasing in the harvested power.

Polyvinylidene fluoride (PVDF) is employed in a wide range of devices based on its excellent mechanical, optical, high thermal, piezoelectric, pyroelectric, and ferroelectric characteristics. In the current investigation, the pristine and neodymium oxide (Nd2O3) nanoparticles embedded polyvinylidene fluoride (PVDF) thick films were prepared via solution casting method. The Nd2O3 nanoparticles were synthesized via hydrothermal technique. The functional groups were identified in the nanocomposite films via infrared vibrational spectroscopy. It revealed the presence of ferroelectric β-phase in the annealed nanocomposite films. All-important optical constants have been determined for the first time via UV-VIS transmission spectroscopy for the nanocomposite films in the ferroelectric phase.

Background Vascular trauma data have been submitted to the American Association for the Surgery of Trauma PROspective Observational Vascular Injury Trial (PROOVIT) database since 2013. We present data to describe current use of endovascular surgery in vascular trauma. Methods Registry data from March 2013 to December 2016 were reviewed. All trauma patients who had an injury to a named artery, except the forearm and lower leg, were included. Arteries were grouped into anatomic regions and by compressible and noncompressible region for analysis. This review focused on patients with noncompressible transection, partial transection, or flow-limiting defect injuries. Bivariate and multivariate analyses were used to assess the relationships between study variables. Results One thousand one hundred forty-three patients from 22 institutions were included. Median age was 32 years (interquartile range, 23-48) and 76% (n = 871) were male. Mechanisms of injury were 49% (n = 561) blunt, 41% (n = 464) penetrating, and 1.8% (n = 21) of mixed aetiology. Gunshot wounds accounted for 73% (n = 341) of all penetrating injuries. Endovascular techniques were used least often in limb trauma and most commonly in patients with blunt injuries to more than one region. Penetrating wounds to any region were preferentially treated with open surgery (74%, n = 341/459). The most common indication for endovascular treatment was blunt noncompressible torso injuries. These patients had higher Injury Severity Scores and longer associated hospital stays, but required less packed red blood cells, and had lower in hospital mortality than those treated with open surgery. On multivariate analysis, admission low hemoglobin concentration and abdominal injury were independent predictors of mortality. Conclusion Our review of PROOVIT registry data demonstrates a high utilization of endovascular therapy among severely injured blunt trauma patients primarily with noncompressible torso hemorrhage. This is associated with a decreased need for blood transfusion and improved survival despite longer length of stay. Level of evidence Therapeutic/care management, level III.

Advancements in our understanding of the causes and correlates of disease mean that we are now able to estimate an individual's level of risk. This, and the ever-increasing need for healthcare interventions to be cost-effective, has led to calls for the introduction of risk-based screening. Risk-based screening would involve the use of information about an individual's risk factors to decide whether or not they should be eligible for screening, or the frequency with which they should be invited to attend screening. Evidence is emerging that targeted screening, towards those at higher risk, can increase the cost-effectiveness of a screening programme. The relationship between individual risk and the cost-effectiveness of screening an individual is implicitly recognised in current population screening programmes in the UK. However, the nature of this relationship, and its implications for cost-effectiveness analysis, has not been presented in the academic literature. In this study we propose that an individual's risk of developing a disease has a consistent and quantifiable relationship with the cost-effectiveness of screening them. We suggest a simple modification to standard methods of cost-effectiveness analysis that enables the incorporation of individual risk. Using numerical examples we demonstrate the nature of the relationship between risk and cost-effectiveness and suggest means of optimising a screening intervention. This can be done either by defining a minimum level of risk for eligibility or by defining the optimal recall period for screening. We suggest that methods of decision modelling could enable such an analysis to be carried out, and that information on individual risk could be used to optimise the cost-effectiveness of population screening programmes.

An aberrant right subclavian artery is a known arch variant with surgical intervention reserved for those patients presenting symptomatically, those with aneurysmal degeneration particularly of a Kommerell diverticulum, or those with adjacent aortic pathology. Varied surgical approaches have been described, often involving a supraclavicular approach in conjunction with a thoracotomy, or more recently, hybrid endovascular techniques. In the absence of aneurysmal degeneration or associated aortic pathology, surgical repair can be performed safely through a single supraclavicular incision. We present a case of a patient repaired in this fashion.

Objectives To evaluate the efficacy, safety, and tolerability of repeated NGX-4010 treatments in the open-label extension phase of a 52-week study in patients with neuropathic pain due to HIV-associated distal sensory polyneuropathy (HIV-DSP). Methods Patients completing the 12-week, randomized, double-blind phase of the study could enter a 40-week, open-label phase, and receive up to 3, 60-minute NGX-4010 treatments. Patients recorded their "average pain for the past 24 hours" daily using the Numeric Pain Rating Scale (NPRS). Efficacy assessment included the percentage NPRS score reduction from baseline to weeks 2 to 12 after the final treatment, and Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) questionnaires at study termination. Results Of 307 patients randomized, 272 entered the open-label phase; 81, 90, 55, and 46 received 0, 1, 2, and 3 retreatments, respectively. The mean percentage decrease in NPRS score from baseline to weeks 2 to 12 after the final treatment was similar in patients receiving single or multiple NGX-4010 treatments (-25.8%, -27.1%, -24.6%, and -22.7% for 1, 2, 3, and 4 NGX-4010 treatments, respectively). PGIC and CGIC results demonstrated a benefit of NGX-4010 treatment through to the end of the study regardless of the number of treatments received. Transient local application site reactions were the most frequently reported adverse events, and were mainly mild to moderate, nonserious, and did not increase with repeated treatment. Discussion Repeated NGX-4010 treatments were generally well tolerated and resulted in consistent reductions in HIV-DSP-associated pain and improvement in patient-reported outcomes.

We exploit model-based Bayesian inference methodologies to analyse lung tumour-derived methylation data from a CpG island in the O6-methylguanine-DNA methyltransferase (MGMT) promoter. Interest is in modelling the changes in methylation patterns in a CpG island in the first exon of the promoter during lung tumour development. We propose four competils of methylation state propagation based on two mechanisms. The first is the location-dependence mechanism in which the probability of a gain or loss of methylation at a CpG within the promoter depends upon its location in the CpG sequence. The second mechanism is that of neighbour-dependence in which gain or loss of methylation at a CpG depends upon the methylation status of the immediately preceding CpG. Our data comprises the methylation status at 12 CpGs near the 5' end of the CpG island in two lung tumour samples for both alleles of a nearby polymorphism. We use approximate Bayesian computation, a computationally intensive rejection-sampling algorithm to infer model parameters and compare models without the need to evaluate the likelihood function. We compare the four proposed models using two criteria: the approximate Bayes factors and the distribution of the Euclidean distance between the summary statistics of the observed and simulated datasets. Our model-based analysis demonstrates compelling evidence for both location and neighbour dependence in the process of aberrant DNA methylation of this MGMT promoter CpG island in lung tumours. We find equivocal evidence to support the hypothesis that the methylation patterns of the two alleles evolve independently.

Objectives: To review clinical outcomes of endovascular treatment of type B aortic dissection. Methods: All patients treated for type B aortic dissection between 2006-2011 were identified from a prospectively maintained registry. Health systems charts and medical correspondences were reviewed. Measured outcomes included resolution of the indication for intervention, additional procedures, and survival at 30 days and 1 year. Results: 55 patients were treated with TEVAR for type B dissection (mean age, 61 14 years), 39 (71%) for acute dissections and 16 (29%) for chronic dissections. Indications for treatment were pain (21), malperfusion (13), aneurysm (6), uncontrolled hypertension (6), expansion (5), and rupture (4). Success, defined by relief of indication and freedom from death or re-intervention at 30 days, was achieved in 87% of patients. Twenty-six additional procedures were performed in 22 patients prior to, or at the time of TEVAR. These included debranching procedures (8), renal stenting (7), Iliac stenting (5), iliac exposure or conduit creation (2), mesenteric stenting (2), thrombectomy (1), and tube thoracostomy (1). Left subclavian artery coverage was required in 23 patients. Spinal ischemia occurred in 4 patients, and lumbar drainage performed in 2 patients. Three patients required reintervention during the study period. Survival was 93% at thirty-days and 78% at one year. Conclusions: TEVAR is effective in the treatment of the complications of both acute and chronic type B aortic dissection. Additional procedures are frequently necessary, but early results indicate favorable outcomes, while reintervention is rare.

During the summer of 2010, three student interns from Sisseton Wahpeton Tribal College along with researchers from South Dakota State University engaged in a pilot project to assess the feasibility of using Landsat imagery to determine water transparency in reservation lakes in northeastern South Dakota. The students were trained to assist with data collection, image processing, and spatial and statistical analyses. Secchi depth measurements and lake algae bloom observations were made on cloud-free Landsat overpass days. Measurement locations were geo-referenced using GPS. Field observations and satellite image classification and interpretation techniques were used to create a land use map for the watershed and explore possible land-use-related causes of the variation in water transparency. The results of this project included a better understanding of the relationship between Landsat images and on site observations of water transparency at first and then land use and water quality in reservation lakes.

During the summer of 2010, three student interns from Sisseton Wahpeton Tribal College along with researchers from South Dakota State University engaged in a pilot project to assess the feasibility of using Landsat imagery to determine water transparency in reservation lakes in northeastern South Dakota. The students were trained to assist with data collection, image processing, and spatial and statistical analyses. Secchi depth measurements and lake algae bloom observations were made on cloud-free Landsat overpass days. Measurement locations were geo-referenced using GPS. Field observations and satellite image classification and interpretation techniques were used to create a land use map for the watershed and explore possible land-use-related causes of the variation in water transparency. The results of this project included a better understanding of the relationship between Landsat images and on site observations of water transparency at first and then land use and water quality in reservation lakes.

Peripheral neuropathy is the most frequent neurological complication of human immunodeficiency virus (HIV)-1 infection and is commonly associated with the development of chronic pain. This open-label, 12-week pilot study assessed the efficacy, tolerability, and safety of a high-concentration capsaicin dermal patch (NGX-4010; capsaicin, 640μg/cm2, 8% w/w) to treat painful HIV-associated distal sensory polyneuropathy (DSP). Eligible patients had moderate-to-severe pain in both feet due to HIV-associated DSP or antiretroviral toxic neuropathy. Patients received a single 60-minute application of the investigational high-concentration capsaicin patch to the affected areas. The primary outcome measure was the mean percent change in numeric pain rating scale (NPRS) during weeks two to 12 postadministration. After a single 60-minute NGX-4010 application, the mean percent change from baseline in "average pain for past 24 hours" NPRS scores during weeks two to 12 was −40% (95% CI: −61%, −19%; P=0.0020). Similar results were observed for "worst pain for past 24 hours" and "pain now" scores. Eight of 12 patients (67%) were treatment responders (≥30% pain decrease). Four of 12 patients (33%) experienced a ≥50% reduction in pain. Treatment was generally well tolerated. Treatment-associated pain was self-limited and could be managed with short-acting opioids. This study demonstrates that treatment of painful HIV-associated neuropathy with a single application of NGX-4010, a high-concentration capsaicin patch, was feasible, well tolerated, and associated with significant reduction in pain over the 12 weeks studied. No safety concerns were identified. Controlled studies of NGX-4010 for the treatment of painful HIV-associated neuropathy are warranted.

The effect of intermittent courses of recombinant interleukin-2 (rIL-2) on HIV-1 load in patients receiving combination antiretroviral therapy remains uncertain. CPCRA 059 was an open-label, randomized, multicenter trial in which 511 patients with HIV-1 infection and CD4+ cell counts ofor = 300/mm3 who were receiving antiretroviral therapy were assigned to receive no rIL-2 (255 patients [controls]) or subcutaneous rIL-2 in dosages of 4.5 MIU (130) or 7.5 MIU (126) twice daily for 5-day courses every 8 weeks to maintain CD4+ cell counts that were twice the baseline value oror = 1,000/mm3. The primary objective of this study was to compare the effects of the two doses of rIL-2 and no rIL-2 on viral load and CD4+ cell counts over 12 months. There was no difference in the following viral load measurements between the rIL-2 treatment groups and the control treatment group: percentage of patients with viral loads of50 copies/mL at 12 months (p =.55), time to viral load ofor = 50 copies/mL for patients who had baseline viral loads of50 copies/mL (p =.35), and change in viral load from baseline for patients who had viral loads ofor = 50 copies/mL at baseline (p =.63). At each follow-up visit, the change in CD4+ cell count from baseline was significantly greater in the rIL-2 treatment groups than in the control treatment group, with a mean difference of 251/mm3 at month 12 (95% confidence interval, 207-295; p.0001). No unanticipated adverse experiences were seen in this trial, to our knowledge the largest randomized evaluation of rIL-2 treatment conducted to date.

The Generic Team Approach is an innovation in residential teamwork which focuses on increasing the involvement of team members in designing and implementing treatment plans. One central team discipline is developed in an attempt to eliminate departmental influence and to balance professional status among team members. In this article, the authors describe the approach and analyze their experience implementing it at the Youth Development Center, a model program for troubled youth.

A recently modified commercial enzyme immunoassay (Gonozyme; Abbott Laboratories, North Chicago, IL) for Neisseria gonorrhoeae antigens was compared with bacteriological culture for diagnostic sensitivity, specificity, and predictive value. A total of 480 specimens were tested by both methods; 355 from females attending a sexually transmitted disease clinic ("high-risk") and 125 from female Family Planning clients ("low-risk"). Sensitivity and specificity of enzyme immunoassay for sexually transmitted disease clinic specimens were 79.7 and 97.9%, respectively (55 positive, 280 negative, 6 false positive, 14 false negative). In the low-risk population, sensitivity and specificity were 100 and 97.5%, respectively (3 positive, 119 negative, 3 false positive, 0 false negative). Despite modification, sensitivity of the method remains low for our sexually transmitted disease clinic population, but the test may have applicability for preliminary screening in low-prevalence settings.

Effects of 10, 20, and 30% N2O on decision-making strategy, reaction-times, sustained attention, the Digit Symbol Substitution Test (DSST), short-term memory and the Clyde Mood Scale were assessed in 12 test subjects. Decision-making strategy, as measured by 2-choice probability-learning, was unaffected by 30% N2O once a strategy had been formulated, but reaction-times were increased. Sustained attention was significantly affected in 33% of our subjects, whereas performance on the DSST and on the short-term memory task was impaired in virtually all subjects. Changes were noted in several mood-scale factors with 30% N2O. No residual drug effects were found.