Efficacy of Electrical Stimulation Intervention in Treating Adults with Dysphagia: A Systematic Review

Purpose: Dysphagia is a term used for a swallowing disorder resulting from problems with the oral cavity, pharynx, esophagus, or gastroesophageal junction. Dysphagia can have significant impacts on an individual’s quality of life and statistics suggest that nearly 15 million adults in the United States present with swallowing disorders. Common medical complications associated with dysphagia are malnutrition, dehydration, aspiration pneumonia, and even death. Traditional dysphagia treatment (TDT) for adults currently consists of diet modification, compensatory strategies involving postural adjustments, and swallowing exercises to strengthen musculature. The objective of this systematic review is to determine whether electrical stimulation (ES) improves swallowing function in adults with dysphagia. Methodology: Four indexed databases were searched to obtain studies pertaining to the use of ES in dysphagia treatment and its success. Application of inclusionary and exclusionary criteria narrowed the results and relevant studies were selected for this systematic review. Studies were also hand-selected and appraised for validity to ensure minimal bias. Results: Results of the selected studies revealed varying statistically significant effects of ES as a treatment for adults with dysphagia. However, many studies suggest ES is most effective in producing positive outcomes when coupled with TDT. Conclusion: The results of the systematic review suggest efficacy of ES is highest when it is used in conjunction with TDT. Studies with statistically significant results reported on only a minor improvement with ES. None of the studies reported negative outcomes related to ES. Additional research is needed to determine overall efficacy of ES as an evidence-based intervention for adults with dysphagia resulting from various etiologies.https://scholarworks.uvm.edu/csdms/1005/thumbnail.jp

Electron-photon interactions in quantum dots : coupled oscillators

A coupled oscillator model is developed for the far infra-red response of a quantum dot, and this model is used to predict the vacuum-held Rabi splittings of a dot-cavity system

Non-Traditional Approaches to Interrogating Genome-Wide SNP Data

The field of human molecular genetics has undergone a substantial technological transformation in the past decade, allowing researchers to identify and analyze genetic variation across the human genome with unprecedented depth and precision. A central goal in utilizing this technological advancement is to discover the genetic variation that underlies complex heritable traits and disorders. In recent years, much of the focus has been on large-scale genome- wide association studies (GWAS) in an attempt to identify effects of common single nucleotide polymorphisms (SNPs) on a phenotype. Progress in this arena, however, has been limited, as validated findings for most phenotypes represent only a small fraction of the variance attributed to genetics known from family and twin studies, leaving a large proportion of heritability to be explained. My research is in large part motivated by the issues surrounding GWAS, as additional methodological techniques and population genetic theory can help explain phenotypic variance unaccounted for by the traditional genetic association design. In my first study, I look at a case/control sample of bipolar disorder, examining how prior information from linkage studies can inform GWAS signals. The primary aim is to ease the burden of multiple-testing correction applied in GWAS using empirically informed weighting to tease out true signals supported by prior genetic evidence. In my second study, I determine the best practices to detect signatures of distant inbreeding, via runs of homozygosity, in genome-wide SNP data. The motivation for studying this phenomenon is due to the extensive evidence of inbreeding depression on fitness related traits, where the effects of recessive or partially recessive alleles are expressed. Using an extensive simulation design, I test multiple programs to determine the optimal method to identify runs of homozygosity caused by distant inbreeding. In my third and final study, I apply my work from the second study to a comprehensive dataset of cognitive measures to understand the extent to which distant inbreeding affects variation in general cognitive ability

Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

Autozygosity occurs when two chromosomal segments that are identical from a common ancestor are inherited from each parent. This occurs at high rates in the offspring of mates who are closely related (inbreeding), but also occurs at lower levels among the offspring of distantly related mates. Here, we use runs of homozygosity in genome-wide SNP data to estimate the proportion of the autosome that exists in autozygous tracts in 9,388 cases with schizophrenia and 12,456 controls. We estimate that the odds of schizophrenia increase by ~17% for every 1% increase in genome-wide autozygosity. This association is not due to one or a few regions, but results from many autozygous segments spread throughout the genome, and is consistent with a role for multiple recessive or partially recessive alleles in the etiology of schizophrenia. Such a bias towards recessivity suggests that alleles that increase the risk of schizophrenia have been selected against over evolutionary time

Genome-wide autozygosity is associated with lower general cognitive ability

Inbreeding depression refers to lower fitness among offspring of genetic relatives. This reduced fitness is caused by the inheritance of two identical chromosomal segments (autozygosity) across the genome, which may expose the effects of (partially) recessive deleterious mutations. Even among outbred populations, autozygosity can occur to varying degrees due to cryptic relatedness between parents. Using dense genome-wide single-nucleotide polymorphism (SNP) data, we examined the degree to which autozygosity associated with measured cognitive ability in an unselected sample of 4854 participants of European ancestry. We used runs of homozygosity-multiple homozygous SNPs in a row-to estimate autozygous tracts across the genome. We found that increased levels of autozygosity predicted lower general cognitive ability, and estimate a drop of 0.6 s.d. among the offspring of first cousins (P=0.003-0.02 depending on the model). This effect came predominantly from long and rare autozygous tracts, which theory predicts as more likely to be deleterious than short and common tracts. Association mapping of autozygous tracts did not reveal any specific regions that were predictive beyond chance after correcting for multiple testing genome wide. The observed effect size is consistent with studies of cognitive decline among offspring of known consanguineous relationships. These findings suggest a role for multiple recessive or partially recessive alleles in general cognitive ability, and that alleles decreasing general cognitive ability have been selected against over evolutionary time.Molecular Psychiatry advance online publication, 22 September 2015; doi:10.1038/mp.2015.120

A recessive genetic model and runs of homozygosity in major depressive disorder

Genome-wide association studies (GWASs) of major depressive disorder (MDD) have yet to identify variants that surpass the threshold for genome-wide significance. A recent study reported that runs of homozygosity (ROH) are associated with schizophrenia, reflecting a novel genetic risk factor resulting from increased parental relatedness and recessive genetic effects. Here, we explore the possibility of such a recessive model in MDD. In a sample of 9,238 cases and 9,521 controls reported in a recent mega-analysis of 9 GWAS we perform an analysis of ROH and common variants under a recessive model. Since evidence for association with ROH could reflect a recessive mode of action at loci, we also conducted a genome-wide association analyses under a recessive model. The genome-wide association analysis using a recessive model found no significant associations. Our analysis of ROH suggested that there was significant heterogeneity of effect across studies in effect (P=0.001), and it was associated with genotyping platform and country of origin. The results of the ROH analysis show that differences across studies can lead to conflicting systematic genome-wide differences between cases and controls that are unaccounted for by traditional covariates. They highlight the sensitivity of the ROH method to spurious associations, and the need to carefully control for potential confounds in such analyses. We found no strong evidence for a recessive model underlying MDD

Joint contributions of rare copy number variants and common SNPs to risk for schizophrenia

Objective: Both rare copy number variants (CNVs) and common single-nucleotide polymorphisms (SNPs) contribute to liability to schizophrenia, but their etiological relationship has not been fully elucidated. The authors evaluated an additive model whereby risk of schizophrenia requires less contribution from common SNPs in the presence of a rare CNV, and tested for interactions. Method: Genetic data from 21,094 case subjects with schizophrenia and 20,227 control subjects from the Psychiatric Genomics Consortium were examined. Three classes of rare CNVs were assessed: CNVs previously associated with schizophrenia, CNVs with large deletions ≥500 kb, and total CNV burden. The mean polygenic risk scores (PRSs) between study subjects with and without rare CNVs were compared, and joint effects of PRS and CNVs on schizophrenia liability were modeled by using logistic regression. Results: Schizophrenia case subjects carrying risk CNVs had a lower polygenic risk than case subjects without risk CNVs but a higher risk than control subjects. For case subjects carrying known risk CNVs, the PRS was diminished in proportion to the effect size of the CNV. The strongly associated 22q11.2 deletion required little added PRS to produce schizophrenia. Large deletions and increased CNV burden were also associated with lower polygenic risk in schizophrenia case subjects but not in control subjects or after removal of known risk CNV carriers. Conclusions: The authors found evidence for interactive effects of PRS and previously associated CNVs for risk for schizophrenia, and the results for large deletions and total CNV burden support an additive model. These findings offer insights into the genetic architecture of schizophrenia by illuminating how different established genetic risk factors act and interact to influence liability to schizophrenia