The Experiences of Younger Adults (18-40 Years) Living with an Implanted Cardioverter Defibrillator (ICD): A Dissertation

Sudden cardiac death (SCD) is responsible for 300,000 deaths in the United States each year. Of these 300,000 deaths, 3,000-5,000 are younger adults (18-40 years) (American Heart Association (AHA), 2005; Sudden Arrhythmia Death Syndromes Foundation (SADS), 2005). Implanted cardioverter defibrillators have become the treatment of choice for individuals with life threatening arrhythmias (Cannom Prystowsky, 2004; Glikson & Friedman, 2001; Josephson, Hein, & Wellens, 2004). Although this life sustaining technology has been found to be effective in terminating life threatening arrhythmias, adjustment to an ICD may be difficult for some patients (Ganz, 2004). Few studies have investigated how younger adults manage life with an ICD (Sears, Burns, Handberg, Sotile, & Conti, 2001). It has been reported that older adults view the ICD as an extension of life, whereas, younger ICD recipients associate the ICD with significant life changes, body image concerns, and decreased independence (Arteaga & Windle, 1995). The purpose of this study was to describe the day-to-day experiences of younger adults (18-40 years old) [N = 20] living with an implanted cardioverter defibrillator. A qualitative descriptive design was used with naturalistic inquiry guiding data collection, management, and analysis. Using open-ended, in-depth interviews, younger adults were asked to describe their life after ICD implantation, physiological or psychosocial issues related to ICD implantation, and strategies used to manage life with an ICD. Data were managed using NVIVO software and analyzed using content analysis. The results revealed an overarching theme, A cautious transition to a new normal, with five subthemes: Initial diagnosis: anxiety and concern; Caution, awareness, and security: daily life with an ICD; Childbearing: passing my disease to my children; Financial concerns; and Strategies for living with an ICD: be positive and live life to the fullest. This study presented some of the unique developmental and transitional issues that younger adults with ICDs are facing and strategies they used to assist in adaptation to life with an ICD. Their experiences can provide the basis for intervention programs that are developmentally sensitive and age-specific

A gendered therapeutic learning landscape : responding creatively to a pandemic

Crafting has occupied the hands and minds of women over many centuries providing vital connections with cultural skills and with community. While the COVID-19 pandemic has isolated women in their homes, it has also provided opportunities for women to reconnect to crafting through virtual spaces. This paper draws on a thematic analysis of a focus group interview examining the experiences of regional women participating in a crafting group and identifies the ways in which they used craft to support their wellbeing. Drawing on the concept of therapeutic landscapes, the paper highlights that connection in a virtual craft group supports lifelong learning and wellbeing, brings women together in support through a community of women’s practice and facilitates opportunities for producing meaningful and commemorative quilting projects This finding has implications for a society experiencing unprecedented levels of stress, mental illness and anxiety about the future. © 2022, Adult Learning Australia. All rights reserved

Sleep Disturbance, Symptoms, Psychological Distress, and Health-Related Quality of Life in Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by elevated pulmonary pressures that lead to right heart failure and premature mortality. Patients experience multiple symptoms including dyspnea, fatigue and chest pain, but little is known about sleep disturbance, PAH symptoms, psychological distress and health-related quality of life (HRQOL) in PAH. Aim: The purpose of this study was to describe the occurrence of sleep disturbance and compare PAH symptoms, psychological distress, and HRQOL across severity of sleep disturbance. Methods: One hundred and ninety-one participants completed a socio-demographic and clinical data form, PAH Symptom Severity Scale, Profile of Mood States (POMS) short form and the Medical Outcomes Short Form-36 (SF-36). Descriptive statistics were used to describe sleep disturbances; analysis of variance models were used to quantify differences in PAH symptoms, psychological distress and HRQOL by sleep disturbance groups. Results: The majority of participants (n=162, 85%) were women with a mean age of 53 years. Sixty-five (34%) reported no sleep disturbance; 54 (28%) mild sleep disturbance; 41 (22%) moderate sleep disturbance; and 31 (16%) severe sleep disturbance. Those reporting higher sleep disturbance severity reported worse PAH symptoms, psychological distress, and HRQOL. Conclusions: Sleep disturbance is a significant finding in PAH. Increasing levels of sleep disturbance are associated with worse PAH symptoms, psychological states, and health-related quality of life. Interventions that decrease sleep disturbances may improve symptoms and HRQOL

Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke

Background and Objectives Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.Peer reviewe

Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20–80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50 000 cosmopolitan tagged SNPs across ∼2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 × 10−6). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β ± SE, 0.048 ± 0.008, P = 7.7 × 10−9) as was rs7302703-G in HOXC10 (β = 0.044 ± 0.008, P = 2.9 × 10−7) and rs936108-C in PEMT (β = 0.035 ± 0.007, P = 1.9 × 10−6). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β = 0.10 ± 0.02, P = 1.9 × 10−6) and rs1037575-A in ATBDB4 (β = 0.046 ± 0.01, P = 2.2 × 10−6), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

AbstractObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation can explain cardioembolic stroke risk.MethodsWe evaluated genetic correlations between a prior genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously-validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors.ResultsWe observed strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson’s r=0.77 and 0.76, respectively, across SNPs with p &lt; 4.4 × 10−4 in the prior AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio (OR) per standard deviation (sd) = 1.40, p = 1.45×10−48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per sd = 1.07, p = 0.004), but no other primary stroke subtypes (all p &gt; 0.1).ConclusionsGenetic risk for AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.</jats:sec

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries