Interferon-gamma (IFNγ) ELISpot and FluoroSpot are widely used assays to detect functional cell responses in immunotherapy clinical studies. Recognized for their importance in vaccine development studies to quantitate immune responses, these assays have more recently risen to the forefront in cell and gene therapy as well as cancer immunotherapy fields where responses against cancer neoantigens are not easily detectable above assay background. Here, we test a new class of fetal bovine serum (FBS), CultraPure FBS, in ex vivo ELISpot and FluoroSpot assays and cultured FluoroSpot assays following in vitro expansion.
View Article and Find Full Text PDFResearch on interpersonal interaction dynamics in relationships between persons with dementia and their family caregivers has been limited. We examine the role of these dynamics in decisions to transition a family member from home care to congregate care, with a particular focus on the role of fear of incompetence. Fear of incompetence is the fear of being unable to interact, communicate in a meaningful way, or take care of a close family member with dementia.
View Article and Find Full Text PDFObjective: The COVID-19 pandemic has placed increased strain on healthcare systems worldwide with enormous reorganisation undertaken to support 'COVID-centric' services. Non-COVID-19 admissions reduced secondary to public health measures to halt viral transmission. We aimed to understand the impact of the response to COVID-19 on the outcomes of upper gastrointestinal (UGI) bleeds.
View Article and Find Full Text PDFPurpose: Short-term exposure to outdoor air pollution has been positively associated with numerous measures of acute morbidity and mortality, most consistently as excess cardiorespiratory disease associated with fine particulate matter (PM), particularly in vulnerable populations. It is unknown if the critically ill, a vulnerable population with high levels of cardiorespiratory disease, is affected by air pollution.
Methods: We performed a time series analysis of emergency cardiorespiratory, stroke and sepsis intensive care (ICU) admissions for the years 2008-2016, using data from the Australian and New Zealand Intensive Care Society Adult Patient Database (ANZICS-APD).
Aims/hypothesis: Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up).
Methods: From a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes).
Objective: Maturity-onset diabetes of the young (MODY) due to variants in is the most common type of monogenic diabetes. Frequent misdiagnosis results in missed opportunity to use sulfonylureas as first-line treatment. A nongenetic biomarker could improve selection of subjects for genetic testing and increase diagnosis rates.
View Article and Find Full Text PDFThe molecular mechanisms underpinning susceptibility loci for type 2 diabetes (T2D) remain poorly understood. Coding variants in peptidylglycine α-amidating monooxygenase (PAM) are associated with both T2D risk and insulinogenic index. Here, we demonstrate that the T2D risk alleles impact negatively on overall PAM activity via defects in expression and catalytic function.
View Article and Find Full Text PDFArthritis Rheumatol
December 2018
Objective: B cells impact the progression of systemic sclerosis (SSc; scleroderma) through multiple pathogenic mechanisms. CD19 inhibition in mice reduced skin thickness, collagen production, and autoantibody levels, consistent with CD19 expression on plasma cells (PCs), the source of antibody production. PC depletion could effectively reduce collagen deposition and inflammation in SSc; therefore, we investigated the effects of PC depletion on SSc disease activity.
View Article and Find Full Text PDFGlucagon-like peptide 1 (GLP-1) stimulated insulin secretion has a considerable heritable component as estimated from twin studies, yet few genetic variants influencing this phenotype have been identified. We performed the first genome-wide association study (GWAS) of GLP-1 stimulated insulin secretion in non-diabetic individuals from the Netherlands Twin register (n = 126). This GWAS was enhanced using a tissue-specific protein-protein interaction network approach.
View Article and Find Full Text PDFThere is perhaps no finding in psychology that is more consistent than the human motivation to avoid negative experiences and seek out positive ones. The current review details some of the aggression-related consequences that result from failures to avoid these negative experiences. Attention is paid to the theoretical processes at work that produce such effects.
View Article and Find Full Text PDFTo investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.
View Article and Find Full Text PDFCultural generality versus specificity of media violence effects on aggression was examined in seven countries (Australia, China, Croatia, Germany, Japan, Romania, the United States). Participants reported aggressive behaviors, media use habits, and several other known risk and protective factors for aggression. Across nations, exposure to violent screen media was positively associated with aggression.
View Article and Find Full Text PDFUnderstanding the physiological mechanisms by which common variants predispose to type 2 diabetes requires large studies with detailed measures of insulin secretion and sensitivity. Here we performed the largest genome-wide association study of first-phase insulin secretion, as measured by intravenous glucose tolerance tests, using up to 5,567 individuals without diabetes from 10 studies. We aimed to refine the mechanisms of 178 known associations between common variants and glycemic traits and identify new loci.
View Article and Find Full Text PDFTo dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues.
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