Structured genome-wide association methods can be used to find population substructure, determine significant SNPs, and subsequently narrow down the field of SNPs to those most significant for determining disease risk. Beginning with more than 500,000 SNPs and rheumatoid arthritis (RA) phenotype data for cases and controls, we used a three-part clustering approach that found 684 SNPs significant for determining RA after accounting for clusters, and of those, 168 SNPs with differing odds across clusters. These 168 SNPs were used to create 16 population subgroups, each revealing a unique pattern of minor allele frequencies. The subgroups showed some commonality in multi-dimensional scaling plots, however, and were combined into five RA risk categories, each with odds differing from the other categories with pvalues less than 0.0001. Thus, based on SNP information from 168 SNPs it may be possible to assign an individual into one of five distinct RA risk categories.

Within the medical field, the demand to store and analyze small sample, large variable data has become ever-abundant. Several two-sample tests for equality of means, including the revered Hotelling’s T2 test, have already been established when the combined sample size of both populations exceeds the dimension of the variables. However, tests such as Hotelling’s T2 become either unusable or output small power when the number of variables is greater than the combined sample size. We propose a test using both prepivoting and Edgeworth expansion that maintains high power in this higher dimensional scenario, known as the “large p small n ” problem. Our test’s finite sample performance is compared with other recently proposed tests designed to also handle the “large p small n ” situation. We apply our test to a microarray gene expression data set and report competitive rates for both power and Type-I error.

To facilitate patient growth, therapists must immerse themselves in the patient’s world while also being able to see what is needed for change. This process requires finding a delicate balance between supporting and pushing patients. Therapists in training are additionally tasked with incorporating supervisors’ suggestions with their own views on what is needed to help their patients. Beginning therapists with tendencies to be overly accommodating may struggle to reconcile these competing demands. Thus, the aim of the present work is to explore how trainee friendly submissiveness (FS) interfaces with psychotherapy. Prior to training, clinical graduate trainee (n = 35) FS was assessed using the Inventory of Interpersonal Problems-32. Process and outcome data were then collected from each therapist’s first training case. Specifically, each trainee was assigned an undergraduate student volunteer with whom they had four non-manualized therapy sessions over the academic semester. After the third session, patients and trainees completed questionnaires assessing session impact and the working alliance, and two expert raters coded third session videotapes for techniques. Following termination, patients rated the overall helpfulness of the therapy. Trainee FS was significantly negatively associated with patient-rated depth, alliance, and overall helpfulness with moderate effects. Findings from a mediation analysis further suggested that trainees with high FS struggled to focus the therapy in a way that felt productive to patients. Implications for clinical training are discussed.

Age-related macular degeneration (AMD) is the leading cause of blindness in people over the age of 50 worldwide. The retinal pigment epithelium (RPE), located in the back of the eye, is most affected in AMD. Nicotinamide adenine dinucleotide (NAD+) is a coenzyme common to most metabolic pathways. Reductions in NAD+ and NAD+- dependent enzymes (e.g., SIRT1) have been linked causally to the development/progression of many age-related pathologies. None, however, have evaluated NAD+ directly or the mechanisms governing its biosynthesis and related availability in RPE. In our previous study, we have shown that NAD+ levels decline with age in the RPE. This correlated directly with decreased nicotinamide phosphoribosyltransferase (NAMPT) expression. SIRT1 expression and activity was also significantly reduced. Using the human RPE cell line, ARPE-19, primary mouse RPE cells and FK866, a highly specific, noncompetitive NAMPT inhibitor, we simulated in vitro the age-dependent decline in NAD+ and the related increase in RPE senescence. Using this model, we demonstrated the positive impact that therapies that provide supplemental or alternate energy sources such as nicotinamide mononucleotide (NMN) and β-hydroxybutyrate (B-HB) have on RPE viability and the possible role of G-protein coupled receptor, GPR109A in this process.