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In this trial, two new programs for delivering implantable cardioverter–defibrillator therapy resulted in fewer inappropriate interventions (shocks or antitachycardia pacing) and an unexpected reduction in mortality. Improved programming could benefit patients with ICDs. The implantable cardioverter–defibrillator (ICD), either alone or in conjunction with cardiac-resynchronization therapy (CRT), is highly effective in reducing the rate of death due to ventricular tachyarrhythmia among high-risk cardiac patients. 1 – 4 However, inappropriate ICD activations, which are typically caused by supraventricular tachyarrhythmias, are frequent, despite sophisticated device-related detection algorithms that are designed to differentiate supraventricular from ventricular tachyarrhythmias; such activations have potentially life-threatening side effects. 5 , 6 Inappropriate device-delivered therapy, defined as therapy delivered for nonventricular tachyarrhythmias, affects 8 to 40% of patients with ICDs. 5 The best method for programming ICD devices to reduce inappropriate therapy is unknown. 7 We conducted a . . .

كتاب نموذج الديناميكيات اللولبية \"في اتقان القيم والقيادة والتغيير\" : كتاب ملهم للمديرين والاستشاريين والخبراء الاستراتيجيين والقادة الذين يخططون لتحقيق نجاح في عالم الأعمالفي القرن الحادي والعشرين، كما يقدم للتنمية البشرية إطار عمل جديد لفهم القيم المحركة للأفراد والمجتمعات، ودراسة درجات الوعي لدى شعوب الأرض ومستوى القيم لديهم في نواحي العمل والحياة الشخصية والتعليم، بل وحتى الجغرافيا السياسية.

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its associated skeletal muscle wasting (SMW) and mortality. Currently, the relationships between PDAC, SMW, and survival are poorly understood. Thus, there is great need for a faithful small animal model with quantitative longitudinal outcome measures that recapitulate clinical PDAC, to define SMW onset and assess progression. Therefore, we aimed to validate dual energy X-ray absorptiometry (DEXA) as a longitudinal measure of lean mass, and demonstrate its utility to quantify SMW in the KCKO murine model of PDAC. In vivo body composition of: 1) untreated mice at 5, 8, 12, 18, and 22 weeks of age (n = 4) and 2) a cohort of mice with (n = 5) and without PDAC (n = 5), was determined via DEXA and lean mass of the lower hind limbs was predicted via a region of interest analysis by two-independent observers. Total body weight was determined. Tibialis anterior (TA) muscles were weighed and processed for histomorphometry immediately post-mortem. Statistical differences between groups were assessed using ANOVA and Student's t-tests. Linear regression models and correlation analysis were used to measure the association between TA and DEXA mass, and reproducibility of DEXA was quantified via the intraclass correlation coefficient (ICC). Lean mass in growing untreated mice determined by DEXA correlated with TA mass (r2 = 0.94; p <0.0001) and body weight (r2 = 0.89; p <0.0001). DEXA measurements were highly reproducible between observers (ICC = 0.95; 95% CI: 0.89-0.98). DEXA and TA mass also correlated in the PDAC cohort (r2 = 0.76; p <0.0001). Significant SMW in tumor-bearing mice was detected within 38 days of implantation, by DEXA, TA mass, and histomorphometry. DEXA is a longitudinal outcome measure of lean mass in mice. The KCKO syngeneic model is a bona fide model of PDAC associated SMW that can be quantified with longitudinal DEXA.

Vessel wall imaging (VWI) using T1 dark blood MRI can depict inflammation of intracranial arteries in patients with cerebral vasculitis. Recently, 3D VWI sequences were introduced at 3 Tesla. We aimed to compare 2D and 3D VWI for detection of intracranial vessel wall enhancement (VWE) in patients suspected of cerebral vasculitis. 44 MRI scans of 39 patients were assessed that included bi-planar 2D T1 and whole-brain 3D T1 SPACE dark blood VWI pre and post contrast. Visibility and VWE were analyzed in 31 pre-specified intracranial artery segments. Additionally, leptomeningeal and parenchymal contrast enhancement was assessed. Overall, more arterial segments were visualized with 3D VWI (p<0.0001). Detection of VWE showed fair agreement between 2D and 3D VWI (κ = 0.583). On segmental level, more VWE was detected in intradural ICA by 2D VWI (p<0.001) and in VA V4 segment by 3D VWI (p<0.05). 3D VWI showed more leptomeningeal (p<0.05) and parenchymal (p<0.01) contrast enhancement. In patients with positive diagnosis of cerebral vasculitis, sensitivity was of 67% (2D and 3D VWI) and specificity was 44% (2D VWI) and 48% (3D VWI); more VWE was seen in arteries distal to VA and ICA compared to non-vasculitic patients. 2D and 3D VWI differed in the ability to detect VWE. Whole brain coverage with better evaluability of VAs and distal intracranial artery segments, and depiction of more parenchymal and leptomeningeal enhancement make 3D VWI more favorable. As VWE in arteries distal to VA and ICA may be used for discrimination of vasculitic and non-vasculitic patients, future increase in spatial resolution of 3D VWI sequences may be beneficial.

Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone1-34 (rPTH1-34) effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34 safety and efficacy in a clinically relevant canine femoral allograft model. Adult female mongrel hounds (n = 20) received a 5cm mid-diaphyseal osteotomy reconstructed with a plated allograft, and were randomized to: 1) Placebo (n = 5; daily saline), 2) Continuous rPTH1-34 (n = 7; 5 μg/kg/day s.c. from day 1-55 post-op), or 3) Delayed rPTH1-34 (n = 8; 5 μg/kg/day s.c. from day 14-28 post-op). Safety was assessed by physical behavior and blood calcium monitoring. Cone beam CT (CB-CT) was performed on days 14, 28 and 56 post-op to assess 2D cortical healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic histomorphometry were also performed. The high drug dose was poorly tolerated, as most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p<0.05). These rPTH1-34 effects were confirmed by histomorphometry, revealing significant increases in mineral apposition rates (MAR) on host bone and graft-host junctions (p<0.05). Delayed rPTH1-34 significantly increased callus volume and MAR at 8 weeks (p<0.05). Although no biomechanical differences were observed, as expected for early healing, the results demonstrated that 2D RUST scoring significantly correlated with torsional biomechanics (p<0.01). In conclusion, 8-weeks of intermittent high-dose rPTH1-34 treatment significantly increases callus formation and accelerates bony union of intercalary massive allografts in a clinically relevant canine model, but with serious side-effects from hypercalcemia.

We investigate the use of relaxed decision diagrams (DDs) for computing admissible heuristics for the cost-optimal delete-free planning (DFP) problem. Our main contributions are the introduction of two novel DD encodings for a DFP task: a multivalued decision diagram that includes the sequencing aspect of the problem and a binary decision diagram representation of its sequential relaxation. We present construction algorithms for each DD that leverage these different perspectives of the DFP task and provide theoretical and empirical analyses of the associated heuristics. We further show that relaxed DDs can be used beyond heuristic computation to extract delete-free plans, find action landmarks, and identify redundant actions. Our empirical analysis shows that while DD-based heuristics trail the state of the art, even small relaxed DDs are competitive with the linear programming heuristic for the DFP task, thus, revealing novel ways of designing admissible heuristics.

A key display characteristic is its efficiency (emitted light power divided by input power). Although display efficiencies are being improved through emissive (for example, quantum dot and organic light-emitting) display designs, which remove the highly inefficient colour filters found in traditional liquid crystal displays, polarization filters, which block about 50% light, remain necessary to inhibit ambient light reflection. We introduce a luminescent concentrator design to replace both colour and polarization filters. Narrow-band, large-Stokes-shift, CdSe/CdS quantum dot emitters are embedded in a luminescent concentrator pixel element with a small top aperture. The remainder of the top surface is coated black, reducing ambient light reflection. A single pixel demonstrates an extraction efficiency of 40.9% from a pixel with an aperture opening of 11.0%. A simple proof-of-concept multipixel array is demonstrated.Inefficient filters and overall efficiency are issues for display technology. Luminescent concentrator pixels have been used with CdSe/CdS quantum dot emitters, which enable both colour and polarization filtering, as well as nearly 41% extraction efficiency.

Background: CrossFit is a type of competitive exercise program that has gained widespread recognition. To date, there have been no studies that have formally examined injury rates among CrossFit participants or factors that may contribute to injury rates. Purpose: To establish an injury rate among CrossFit participants and to identify trends and associations between injury rates and demographic categories, gym characteristics, and athletic abilities among CrossFit participants. Study Design: Descriptive epidemiology study. Methods: A survey was conducted, based on validated epidemiologic injury surveillance methods, to identify patterns of injury among CrossFit participants. It was sent to CrossFit gyms in Rochester, New York; New York City, New York; and Philadelphia, Pennsylvania, and made available via a posting on the main CrossFit website. Participants were encouraged to distribute it further, and as such, there were responses from a wide geographical location. Inclusion criteria included participating in CrossFit training at a CrossFit gym in the United States. Data were collected from October 2012 to February 2013. Data analysis was performed using Fisher exact tests and chi-square tests. Results: A total of 486 CrossFit participants completed the survey, and 386 met the inclusion criteria. The overall injury rate was determined to be 19.4% (75/386). Males (53/231) were injured more frequently than females (21/150; P = .03). Across all exercises, injury rates were significantly different (P < .001), with shoulder (21/84), low back (12/84), and knee (11/84) being the most commonly injured overall. The shoulder was most commonly injured in gymnastic movements, and the low back was most commonly injured in power lifting movements. Most participants did not report prior injury (72/89; P < .001) or discomfort in the area (58/88; P < .001). Last, the injury rate was significantly decreased with trainer involvement (P = .028). Conclusion: The injury rate in CrossFit was approximately 20%. Males were more likely to sustain an injury than females. The involvement of trainers in coaching participants on their form and guiding them through the workout correlates with a decreased injury rate. The shoulder and lower back were the most commonly injured in gymnastic and power lifting movements, respectively. Participants reported primarily acute and fairly mild injuries.

Background Because immunity against Staphylococcus aureus has not been fully elucidated, there is no diagnostic test to gauge how robust a patient’s host response is likely to be. Therefore, we aimed to develop a test for specific antibodies in serum with diagnostic and prognostic potential. Questions/Purposes We describe the development and validation of a multiplex immunoassay for characterizing a patient’s immune response against 14 known S aureus antigens, which we then used to answer four questions: (1) Do certain antigens predominate in the immune response against S aureus ? (2) Is there a predominant pattern of antigens recognized by patients and mice with infections? (3) Is the immunoglobulin G (IgG) response to any single antigen a useful predictor of ongoing S aureus infection? (4) Does measurement of the combined response against all 14 antigens provide a better predictor of ongoing infection? Methods A case-control study was performed. Sera were collected from 35 consecutive patients with S aureus culture-confirmed (methicillin-sensitive S aureus or methicillin-resistant S aureus ) musculoskeletal infections (deep implant-associated, osteomyelitis, and cases of established septic arthritis). Patients were excluded only if they did not give informed consent for participation. Twenty-four patients had implant infections after total joint replacements, five had fracture implant infections, four had native knee infections, and two had chronic osteomyelitis without an implant. Control patients were chosen from a group of healthy, medically optimized patients scheduled to undergo elective arthroplasty. Control patients were matched for age (± 3 years), BMI (± 3 kg/m 2 ), and sex as closely as possible to patients with infections. Sera from patients with S aureus infections and murine S aureus tibial implant infections were used to evaluate a multiplex immunoassay for immunoglobulin titers against 14 recombinant S aureus antigens. All patients were treated with organism-targeted antibiotic therapy and appropriate, timely surgery. Treatment response was monitored with clinical examination, erythrocyte sedimentation rate, C-reactive protein, and resampling of the infection site for the pathogen as needed. Elevated inflammatory markers or persistent positive culture results were considered evidence of ongoing infection. Treatment provided was considered standard-of-care therapy in our medical center and all patients were treated jointly with a board-certified infectious disease specialist. Results Four antigens elicited more than 65% of the measurable IgG, the most dominant being against iron-regulated surface determinant protein B (IsdB). Patients with infections had different patterns of elevated IgG titers, so that no single titer was elevated in more than 50% of patients with infections (area under the curve [AUC] ≤ 0.80). Multivariate analysis of IgG titers yielded greater predictive power of S aureus infection (AUC = 0.896). Patients with infections who had high titers against IsdB (median of survivors, 7.28 [25%–75% range, 2.22–21.26] vs median of patients with infection-related death, 40.41 [25%–75% range, 23.57–51.37], difference of medians, 33.13; p = 0.043) and iron-regulated surface determinant protein A (IsdA) median of survivors, 2.21 [25%–75% range, 0.79–9.11] vs median of patients with infection-related death, 12.24 [25%–75% range, 8.85–15.95], difference of medians, 10.03; p = 0.043) were more likely to die from infections than those who did not have high titers of IsdB. Conclusions Measurement of the host antibody response is a predictor of ongoing infection that may prove to have prognostic value. Future studies will seek to enlarge the patient population with infections to allow us to reduce the number of antigens required to achieve a stronger predictive power. Clinical Relevance Measurement of the immune response against S aureus with this diagnostic tool may help guide future studies on prophylaxis and therapy in an era of personalized medicine and pathogen-specific therapies.