Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

Connectivity and Centrality Characteristics of the Epileptogenic Focus Using Directed Network Analysis

Accurate epileptogenic focus localization is required prior to surgical resection of brain tissue for the treatment of patients with antiepileptic drug-resistant (intractable) epilepsy. This clinical need is only partially fulfilled through a subjective, and at times inconclusive, the evaluation of the recorded electroencephalogram (EEG) at seizures\u27 onset (the so-called gold standard for focus localization in epilepsy). We herein present a novel method of multivariate analysis of the EEG that appears to be very promising for an objective and robust localization of the epileptogenic focus at seizures\u27 onset. Using the measure of generalized partial directed coherence, combined with surrogate data analysis, we first estimated from multichannel intracranial EEG the statistically significant causal interactions between brain regions at the onset of 92 clinical seizures from nine patients with temporal lobe intractable epilepsy. From the networks that were formed based on the thus derived interactions, a set of centrality metrics was estimated per network node (brain site). Brain sites located anatomically within the epileptogenic focus were shown to be associated with greater inward centrality values than non-focal brain regions at high frequencies ( γ band), and particular inward centrality metrics accurately localized the focus in all nine patients. In addition to focus localization from seizure (ictal) onset, the developed novel framework for analysis of EEG could be employed to identify the changes of the focal network over time, peri-ictally and interictally, and thus shed light onto the dynamics of ictogenesis, which could then have a significant impact on automated prediction and closed-loop control of seizures by neuromodulation

Plastic Surgeon Compliance with National Safety Initiatives: Clinical Outcomes and Never Events .

BACKGROUND: Venous thromboembolism and surgical-site infection have been identified as preventable complications that are addressed by the National Quality Forum and the Surgical Care Improvement Project. The authors examined compliance of faculty with venous thromboembolism and surgical-site infection prophylaxis and incidence of adverse outcomes in patients at risk. METHODS: The authors performed retrospective chart reviews on 243 patients who underwent abdominoplasty or panniculectomy from 2000 to 2007 and documented demographics and adverse outcomes. Analysis was completed using Pearson\u27s chi-square and Fisher\u27s exact test for categorical variables. Significance was set at p \u3c 0.05. Obesity was defined as body mass index more than 30 and morbid obesity was defined as body mass index more than 40. RESULTS: Of 243 patients, 144 (59 percent) were obese. Seventeen patients (7 percent) suffered complications. All 243 patients received at least one form of venous thromboembolism prophylaxis. One patient had a deep venous thrombosis, and two had pulmonary embolism. These three patients were morbidly obese. Seventy-four percent of patients received appropriate antibiotics. Thirteen patients (5.3 percent) developed significant postoperative infection requiring hospitalization, 12 (92 percent) of whom received appropriate antibiotics. Eleven of these 13 patients (85 percent) were obese, and seven (54 percent) were morbidly obese. Obesity proved to be the only significant risk factor (p \u3e 0.05). CONCLUSIONS: Despite very good compliance with safe practice initiatives, significant adverse outcomes occurred. Obesity was the only pervasive risk factor. This study highlights the potential need for compliance with quality measures and demonstrates that adverse outcomes may result despite adherence to best surgical practices

Imaging versus electrographic connectivity in human mood-related fronto-temporal networks

BackgroundThe efficacy of psychiatric DBS is thought to be driven by the connectivity of stimulation targets with mood-relevant fronto-temporal networks, which is typically evaluated using diffusion-weighted tractography.ObjectiveLeverage intracranial electrophysiology recordings to better predict the circuit-wide effects of neuromodulation to white matter targets. We hypothesize strong convergence between tractography-predicted structural connectivity and stimulation-induced electrophysiological responses.MethodsEvoked potentials were elicited by single-pulse stimulation to two common DBS targets for treatment-resistant depression - the subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VCVS) - in two patients undergoing DBS with stereo-electroencephalographic (sEEG) monitoring. Evoked potentials were compared with predicted structural connectivity between DBS leads and sEEG contacts using probabilistic, patient-specific diffusion-weighted tractography.ResultsEvoked potentials and tractography showed strong convergence in both patients in orbitofrontal, ventromedial prefrontal, and lateral prefrontal cortices for both SCC and VCVS stimulation targets. Low convergence was found in anterior cingulate (ACC), where tractography predicted structural connectivity from SCC targets but produced no evoked potentials during SCC stimulation. Further, tractography predicted no connectivity to ACC from VCVS targets, but VCVS stimulation produced robust evoked potentials.ConclusionThe two connectivity methods showed significant convergence, but important differences emerged with respect to the ability of tractography to predict electrophysiological connectivity between SCC and VCVS to regions of the mood-related network. This multimodal approach raises intriguing implications for the use of tractography in surgical targeting and provides new data to enhance our understanding of the network-wide effects of neuromodulation

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

Reconstructive Plastic Surgery An Atlas of Essential Procedures

A reader-friendly, how-to guide on reconstructive plastic surgery from international experts Reconstructive Plastic Surgery: An Atlas of Essential Procedures edited by esteemed authors, educators, and surgeons Robert X. Murphy Jr. and Charles K. Herman is a comprehensive resource detailing head-to-toe surgical procedures for a broad range of conditions. The senior editors have more than 50 years of collective surgical experience and expertise training hundreds of medical students and plastic surgery residents. A distinguished and diverse group of contributors from more than 15 countries and five continents share clinical pearls throughout the book. Sixty-seven chapters organized in five sections start with head and neck chapters detailing cleft palate defects and repair, followed by functional rhinoplasty, neoplasms, and trauma. Section two encompasses breast reduction/reconstruction techniques and other breast deformities; and management of trunk ulcers, deep wounds, and defects. The hand and upper extremity section details reconstructive techniques for infections, trauma, and Dupuytren's contracture. The final two sections cover a wide spectrum of nerve-related conditions and syndromes, followed by burns, melanoma, and vascular anomalies. Key Features High-quality illustrations and intraoperative photographs enhance understanding of step-by-step operative procedures More than 30 procedural videos provide hands-on guidance on how to perform specific steps in reconstructive plastic surgery A broad range of reconstructive techniques cover trauma, tumor resection, burns, congenital deformities, and degenerative conditions Consistent chapter formatting includes a clear and concise introduction, discussion of pertinent anatomy, surgical indications, operative techniques, complications, and long-term results This highly accessible yet comprehensive procedural guide is must-have reading for medical students, plastic surgery residents, and early-career plastic surgeons. It will also benefit veteran reconstructive plastic surgeons looking for a robust refresher with an international perspective