Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurofibromatosis (Von Recklinghausen Disease) Genetics, Cell Biology and Biochemistry. (Advances in Neurology, Vol. 29.)

epilepsy? , The different types of epileptic seizure, The causes of epilepsy, The first seizure and the investigation of epilepsy, Treatment, Longterm outlook, Living with epilepsy-practical points, Febrile convulsions, The promise of the future. His chapter on Living with Epilepsy comes nearest to dealing with many of the questions raised by the Laidlaws. Both books are aimed at patients and their relatives, the former is best for dispersing their anxieties, the latter for providing more detailed factual information about the disorder. Indeed the latter could be read with profit by any physician looking for a concise account of epilepsy and its treatment. The books complement each other and can be warmly recommended.
Examining Markers in 8q24 to Explain Differences in Evidence for Association With Cleft Lip With/Without Cleft Palate Between Asians and Europeans

In a recent genome‐wide association study (GWAS) from an international consortium, evidence of linkage and association in chr8q24 was much stronger among nonsyndromic cleft lip/palate (CL/P) case‐parent trios of European ancestry than among trios of Asian ancestry. We examined marker information content and haplotype diversity across 13 recruitment sites (from Europe, United States, and Asia) separately, and conducted principal components analysis (PCA) on parents. As expected, PCA revealed large genetic distances between Europeans and Asians, and a north‐south cline from Korea to Singapore in Asia, with Filipino parents forming a somewhat distinct Southeast Asian cluster. Hierarchical clustering of SNP heterozygosity revealed two major clades consistent with PCA results. All genotyped SNPs giving P < 10−6 in the allelic transmission disequilibrium test (TDT) showed higher heterozygosity in Europeans than Asians. On average, European ancestry parents had higher haplotype diversity than Asians. Imputing additional variants across chr8q24 increased the strength of statistical evidence among Europeans and also revealed a significant signal among Asians (although it did not reach genome‐wide significance). Tests for SNP‐population interaction were negative, indicating the lack of strong signal for 8q24 in families of Asian ancestry was not due to any distinct genetic effect, but could simply reflect low power due to lower allele frequencies in Asians. Genet. Epidemiol. 36:392–399, 2012. © 2012 Wiley Periodicals, Inc.
A Fast and Noise‐Resilient Approach to Detect Rare‐Variant Associations With Deep Sequencing Data for Complex Disorders

Next generation sequencing technology has enabled the paradigm shift in genetic association studies from the common disease/common variant to common disease/rare‐variant hypothesis. Analyzing individual rare variants is known to be underpowered; therefore association methods have been developed that aggregate variants across a genetic region, which for exome sequencing is usually a gene. The foreseeable widespread use of whole genome sequencing poses new challenges in statistical analysis. It calls for new rare‐variant association methods that are statistically powerful, robust against high levels of noise due to inclusion of noncausal variants, and yet computationally efficient. We propose a simple and powerful statistic that combines the disease‐associated P‐values of individual variants using a weight that is the inverse of the expected standard deviation of the allele frequencies under the null. This approach, dubbed as Sigma‐P method, is extremely robust to the inclusion of a high proportion of noncausal variants and is also powerful when both detrimental and protective variants are present within a genetic region. The performance of the Sigma‐P method was tested using simulated data based on realistic population demographic and disease models and its power was compared to several previously published methods. The results demonstrate that this method generally outperforms other rare‐variant association methods over a wide range of models. Additionally, sequence data on the ANGPTL family of genes from the Dallas Heart Study were tested for associations with nine metabolic traits and both known and novel putative associations were uncovered using the Sigma‐P method.
Multiway Admixture Deconvolution Using Phased or Unphased Ancestral Panels

We describe a novel method for inferring the local ancestry of admixed individuals from dense genome‐wide single nucleotide polymorphism data. The method, called MULTIMIX, allows multiple source populations, models population linkage disequilibrium between markers and is applicable to datasets in which the sample and source populations are either phased or unphased. The model is based upon a hidden Markov model of switches in ancestry between consecutive windows of loci. We model the observed haplotypes within each window using a multivariate normal distribution with parameters estimated from the ancestral panels. We present three methods to fit the model—Markov chain Monte Carlo sampling, the Expectation Maximization algorithm, and a Classification Expectation Maximization algorithm. The performance of our method on individuals simulated to be admixed with European and West African ancestry shows it to be comparable to HAPMIX, the ancestry calls of the two methods agreeing at 99.26% of loci across the three parameter groups. In addition to it being faster than HAPMIX, it is also found to perform well over a range of extent of admixture in a simulation involving three ancestral populations. In an analysis of real data, we estimate the contribution of European, West African and Native American ancestry to each locus in the Mexican samples of HapMap, giving estimates of ancestral proportions that are consistent with those previously reported.
Palliative Care for End-Stage Lung Disease Patients

Although the length of survival in end-stage lung disease (ESLD) patients is difficult to predict, it is the physician’s role to initiate end-of-life (EOL) discussions with the patient and to facilitate advance medical planning (AMP). AMP should evolve by continuing communication between physician, patient, and patient’s proxy, and the informed choices that the patient makes should be recorded. Home-based hospice care is an option that should be included in EOL discussions. The goal of palliative care should be to provide the best quality of life (QOL) for the patient by symptom relief through pharmacologic and nonpharmacologic modalities. Dyspnea is a common and distressing symptom for ESLD patients. Opioids (nonnebulized forms), bronchodilators (short-acting beta-2 agonists), oxygen, and pulmonary rehabilitation and inspiratory muscle training provide dyspnea relief and may improve QOL. Neither fear of respiratory depression nor addiction should deter physicians from using opioids to relieve dyspnea in ESLD patients. The dose of opioids needed to relieve dyspnea is less than needed for pain relief, and improvement in breathlessness can be achieved without a significant increase in arterial carbon dioxide level. Although Medicare criteria used for long-term oxygen treatment are based on oxygen saturation or tension measurements, these criteria are waived when oxygen is used for palliation of dyspnea in patients enrolled in a hospice program. Short-acting beta-2 agonists should be tried on all dyspneic ESLD patients and maintained if the patient notes improvement in dyspnea. Additional bronchodilator(s) may help some patients. Cough, anxiety, depression, delirium, and other symptoms must be controlled with appropriate medications. Time spent in an unhurried manner with the ESLD patient and family with sensitivity and responsiveness to their needs is a major contribution that a physi-
Geriatric vestibulopathy assessment and management

Purpose of reviewThis review discusses the demographics of dizziness in the older person, the evaluation of the older dizzy patient and how the treatment of dizziness in older patients differs from that in younger individuals. Recent findingsSeven percent of all visits to primary care physicians for patients older than 65 years of age are for dizziness, and dizziness is the most common complaint for patients older than 75 years. In a German study, the 12-month prevalence of vertigo in the general population was 5% with an incidence of 1.4% in adults overall. For individuals aged 60–69 the 12-month prevalence was found to be 7.2% and in individuals 70 years of age or older 8.9%. Data from the United States National Health and Nutrition Examination Surveys indicated that the prevalence of vestibular dysfunction for individuals in the seventh decade of life, eighth decade of life, and older was 49.4, 68.7, and 84.8 percent, respectively. Only subtle age effects are seen on caloric and rotational testing whereas vestibular evoked myogenic potentials (VEMPs) change somewhat with age. Particle repositioning for benign paroxysmal positional vertigo combined with vestibular rehabilitation is more effective than only performing the repositioning maneuver. Tai Chi appears to be an effective intervention for older adults at risk for falling. SummaryWhen caring for an older dizzy patient always assess medication use, perform a Dix–Hallpike maneuver, obtain orthostatic vital signs, discuss fall risk precautions, and consider referral for vestibular rehabilitation.
Accounting for Population Stratification in DNA Methylation Studies

DNA methylation is an important epigenetic mechanism that has been linked to complex diseases and is of great interest to researchers as a potential link between genome, environment, and disease. As the scale of DNA methylation association studies approaches that of genome‐wide association studies, issues such as population stratification will need to be addressed. It is well‐documented that failure to adjust for population stratification can lead to false positives in genetic association studies, but population stratification is often unaccounted for in DNA methylation studies. Here, we propose several approaches to correct for population stratification using principal components (PCs) from different subsets of genome‐wide methylation data. We first illustrate the potential for confounding due to population stratification by demonstrating widespread associations between DNA methylation and race in 388 individuals (365 African American and 23 Caucasian). We subsequently evaluate the performance of our PC‐based approaches and other methods in adjusting for confounding due to population stratification. Our simulations show that (1) all of the methods considered are effective at removing inflation due to population stratification, and (2) maximum power can be obtained with single‐nucleotide polymorphism (SNP)‐based PCs, followed by methylation‐based PCs, which outperform both surrogate variable analysis and genomic control. Among our different approaches to computing methylation‐based PCs, we find that PCs based on CpG sites chosen for their potential to proxy nearby SNPs can provide a powerful and computationally efficient approach to adjust for population stratification in DNA methylation studies when genome‐wide SNP data are unavailable.
Detecting Maternal‐Fetal Genotype Interactions Associated With Conotruncal Heart Defects: A Haplotype‐Based Analysis With Penalized Logistic Regression

Nonsyndromic congenital heart defects (CHDs) develop during embryogenesis as a result of a complex interplay between environmental exposures, genetics, and epigenetic causes. Genetic factors associated with CHDs may be attributed to either independent effects of maternal or fetal genes, or the intergenerational interactions between maternal and fetal genes. Detecting gene‐by‐gene interactions underlying complex diseases is a major challenge in genetic research. Detecting maternal‐fetal genotype (MFG) interactions and differentiating them from the maternal/fetal main effects has presented additional statistical challenges due to correlations between maternal and fetal genomes. Traditionally, genetic variants are tested separately for maternal/fetal main effects and MFG interactions on a single‐locus basis. We conducted a haplotype‐based analysis with a penalized logistic regression framework to dissect the genetic effect associated with the development of nonsyndromic conotruncal heart defects (CTD). Our method allows simultaneous model selection and effect estimation, providing a unified framework to differentiate maternal/fetal main effect from the MFG interaction effect. In addition, the method is able to test multiple highly linked SNPs simultaneously with a configuration of haplotypes, which reduces the data dimensionality and the burden of multiple testing. By analyzing a dataset from the National Birth Defects Prevention Study (NBDPS), we identified seven genes (GSTA1, SOD2, MTRR, AHCYL2, GCLC, GSTM3, and RFC1) associated with the development of CTDs. Our findings suggest that MFG interactions between haplotypes in three of seven genes, GCLC, GSTM3, and RFC1, are associated with nonsyndromic conotruncal heart defects.
The role of botulinum toxin in the management of airway compromise due to bilateral vocal fold paralysis

Purpose of reviewThe management of a patient with bilateral vocal fold motion impairment (BVFMI) can be challenging for the otolaryngologist. The treatment traditionally involves tracheotomy, which can be very distressful for some patients. Alternatively, there are endoscopic procedures, which irreversibly sacrifice voice in order to improve airway. The optimal treatment of BVFMI still eludes us. The purpose of this review is to highlight an alternate management strategy for bilateral vocal fold paralysis using botulinum toxin (BTX). This procedure is predicated on the premise that vocal fold immobility is related to synkinetic reinnervation of the vocal fold. Eliminating any thyroarytenoid/lateral cricoarytenoid (LCA) activity during respiratory gestures should allow greater unopposed posterior cricoarytenoid abduction. Recent findingsThere have been several case reports and series, the largest of which involved 11 patients, describing the successful use of BTX for this application. SummaryThe best candidates for this adductor chemical denervation are those patients who have undergone trauma to the recurrent laryngeal nerve without evidence of cricoarytenoid joint fixation. Patients should have evidence of voluntary thyroarytenoid/LCA laryngeal electromyography activity, though true synkinesis cannot always be reliably identified. The procedure can be another management option for patients with BVFMI.
Sunlight, iron and radicals to tackle the resistant leftovers of biotreated winery wastewater

Winery wastewater is characterized by high organic content consisting of alcohols, acids and recalcitrant high-molecular-weight compounds ( e.g. polyphenols, tannins and lignins). So far, biological treatment constitutes the best available technology for such effluents that are characterized by high seasonal variability; however the strict legislation applied on the reclamation and reuse of wastewaters for irrigation purposes introduces the need for further treatment of the bioresistant fraction of winery effluents. In this context, the use of alternative treatment technologies, aiming to mineralize or transform refractory molecules into others which could be further biodegraded, is a matter of great concern. In this study, a winery effluent that had already been treated in a sequencing batch reactor was subjected to further purification by homogeneous and heterogeneous solar Fenton oxidation processes. The effect of various operating variables such as catalyst and oxidant concentration, initial pH, temperature and lamp power on the abatement of chemical oxygen demand (COD), dissolved organic carbon (DOC), color, total phenolics and ecotoxicity has been assessed in the homogeneous solar Fenton process. In addition, a comparative assessment between homogeneous and heterogeneous solar Fenton processes was performed. In the present study the homogeneous solar Fenton process has been demonstrated to be the most effective process, yielding COD, DOC and total phenolics removal of about 69%, 48% and 71% in 120 min of the photocatalytic treatment, respectively.
Idiopathic rhinitis

Purpose of reviewDue to the overlap of symptoms and signs in the various types of rhinitis, arriving at a precise diagnosis can be difficult. A diagnosis of idiopathic rhinitis can only be used when all other causes have been excluded and this review tries to clarify whom this term should be applied to, and the reasons why. Recent findingsThe current literature on idiopathic rhinitis is sparse. Haematological and immunological tests can help to distinguish which individuals have a predisposition to allergic mediated disease, but these results should be interpreted with caution because of the prevalence of false-positives. It has recently been shown that some patients previously labelled as ‘idiopathic’ suffer from a highly localized form of IgE-mediated allergy known as ‘entopy’. Patients with idiopathic rhinitis probably represent a disparate group who may be suffering from a range of immunological or neuroregulatory disease processes in which an inability to down-regulate inflammatory processes may be as important as the process that initiates it. SummaryTo arrive at a diagnosis of idiopathic rhinitis all other forms of rhinitis must be excluded. With further research and a better understanding of the pathological processes involved in rhinitis, we may need to use the term ‘idiopathic’ less frequently but be more assured of its correct usage.
Prevalence and recurrence rate of colonic lesions in acromegalic patients

Acromegaly is associated with an increased prevalence of colonic polyps. The aim of this study was to evaluate the prevalence and recurrence rate of colonic polyps in acromegalic patients. Ninety-six acromegalic patients and 100 irritable bowel syndrome patients (IBS) were enrolled in the study. Twenty patients who were cured exclusively by surgery, and 20 patients that could not be hormonally controlled were re-examined colonoscopically after 36 months. Twenty-nine of 96 acromegalic patients (30.2%) had colonic polyps. In the IBS group, 10 (10.0%) had colonic polyps. The prevalence of colonic polyps was significantly higher in acromegaly. The group of acromegalic patients with and without polyps did not differ significantly with regard to plasma GH, IGF-I, fasting insulin levels and glycemic status. The presence of colonic polyps was correlated with increased patient age and male gender. We did not observe a difference in terms of polyp recurrence frequencies in the patients cured by surgery compared to uncontrolled patients. Acromegalic patients have a higher prevalence of colonic polyps than that of control subjects. We could not identify any factors that could predict polyps within the acromegalic patients - but age and male sex.
Replacing semicircular canal function with a vestibular implant

Purpose of reviewTo summarize the recent progress in the development of vestibular implants. The review is timely because of the recent advances in the field and because MED-EL has recently announced that they are developing a vestibular implant for clinical applications. Recent findingsThe handicap experienced by patients suffering from bilateral vestibulopathy has a strong negative impact on physical and social functioning that appears to justify a surgical intervention. Two different surgical approaches to insert electrodes to stimulate ampullary neurons have been shown to be viable. The three-dimensional vestibulo-ocular reflex in rhesus monkeys produced with a three-dimensional vestibular implant showed gains that were relatively normal during acute stimulation. Rotation cues provided by an implant interact with otolith cues in a qualitatively normal manner. The brain appears to adapt plastically to the cues provided via artificial electrical stimulation. SummaryResearch to date includes just a few human studies, but available data from both humans and animals support the technological and physiological feasibility of vestibular implants. Although vestibular implant users should not expect normal vestibular function – any more than cochlear implant users should expect normal hearing – data suggest that significant functional improvements are possible.
Narrow band imaging in endoscopic evaluation of the larynx

Purpose of reviewNarrow band imaging (NBI) is a novel endoscopic technique using filtered wavelengths in order to enhance the microvascular abnormalities associated with the preneoplastic and neoplastic changes of the mucosal lining of the upper aerodigestive tract. The present review is focused on the use of NBI in the management of patients with laryngeal cancer. Recent findingsThe larynx and hypopharynx represent an ideal site for NBI application because their thin, nonkeratinized, stratified squamous epithelium permits optimal visualization of the subtle neoangiogenic changes associated with precancerous and neoplastic diseases, including benign processes like recurrent respiratory papillomatosis. These abnormal vascular patterns have been recently described in great detail and demonstrated to be useful diagnostic tools in different settings of laryngeal cancer management: from preoperative diagnosis and staging to intraoperative evaluation of microsurgical margins and posttreatment follow-up. Particularly intriguing is the capacity of NBI to properly distinguish postactinic changes from persistent/recurrent disease. SummaryFrom different institutions in several countries, NBI continues to receive confirmations of its validity as an ancillary diagnostic tool for endoscopic evaluation of oncologic patients. This also holds true for laryngeal and hypopharyngeal neoplastic diseases.
I'll Always Want More: Complex Issues in HIV Palliative Care

This article describes the complex issues in palliative care of a woman with HIV disease, multiple psychiatric issues, and a substance abuse disorder. She went from a state near death to having the opportunity to make peace with her family and before expecting to die. This article describes the multiple transitions faced by this patient and her providers as she continues to live and question the meaning and purpose of her life.
Pediatric status epilepticus management

Purpose of review This review discusses the management of status epilepticus in children, including both anticonvulsant medications and overall management approaches. Recent findings Rapid management of status epilepticus is associated with a greater likelihood of seizure termination and better outcomes, yet data indicate that there are often management delays. This review discusses an overall management approach aiming to simultaneously identify and manage underlying precipitant causes, administer anticonvulsants in rapid succession until seizures have terminated, and identify and manage systemic complications. An example management pathway is provided. Summary Status epilepticus is a common neurologic emergency in children and requires rapid intervention. Having a predetermined status epilepticus management pathway can expedite management.