Improving the Success of Transfer Students: Responding to Risk Factors

How can learning communities be designed to reduce transfer student stress and enhance their learning? This study was designed to investigate the impact of the Criminal Justice Transfer Learning Community experience on its participants’ level of identified stressors over time and their means of coping with those stressors. The Criminal Justice Transfer Learning Community extended for two terms, and was designed to facilitate students’ integration into the university and the criminal justice community. Students in the learning community were asked on multiple occasions to identify stressors and rate their intensity. According to the students, the largest impact on stress reduction was the feeling of belonging to their learning community cohort and the university community

Effective Lagrangian for sˉbg\bar{s}bg and sˉbγ\bar{s}b\gamma Vertices in the mSUGRA model

Complete expressions of the $\bar{s}bg$ and $\bar{s}b\gamma$ vertices are derived in the framework of supersymmetry with minimal flavor violation. With the minimal supergravity (mSUGRA) model, a numerical analysis of the supersymmetric contributions to the Wilson Coefficients at the weak scale is presented.Comment: 12 pages + 7 ps figures, Late

An action for the exact string black hole

A local action is constructed describing the exact string black hole discovered by Dijkgraaf, Verlinde and Verlinde in 1992. It turns out to be a special 2D Maxwell-dilaton gravity theory, linear in curvature and field strength. Two constants of motion exist: mass M>1, determined by the level k, and U(1)-charge Q>0, determined by the value of the dilaton at the origin. ADM mass, Hawking temperature T_H \propto \sqrt{1-1/M} and Bekenstein-Hawking entropy are derived and studied in detail. Winding/momentum mode duality implies the existence of a similar action, arising from a branch ambiguity, which describes the exact string naked singularity. In the strong coupling limit the solution dual to AdS_2 is found to be the 5D Schwarzschild black hole. Some applications to black hole thermodynamics and 2D string theory are discussed and generalizations - supersymmetric extension, coupling to matter and critical collapse, quantization - are pointed out.Comment: 41 pages, 2 eps figures, dedicated to Wolfgang Kummer on occasion of his Emeritierung; v2: added ref; v3: extended discussion in sections 3.2, 3.3 and at the end of 5.3 by adding 2 pages of clarifying text; updated refs; corrected typo

An Application of the Concept of the Therapeutic Alliance To Sadomasochistic Pathology

This paper traces the history of the therapeutic alliance concept, examining how it has been used and misused, at times elevated to a central position and at others rejected altogether. The loss of this concept created a vacuum in classical psychoanalysis that has been filled by rival theories. The continuing usefulness of looking at the treatment process through the lens of the therapeutic alliance, particularly in relation to the manifold difficulties of working with sadomasochistic pathology, is suggested. To this end, revisions of the theory of the therapeutic alliance are suggested to address some of the difficulties that have arisen in conceptualizing this aspect of the therapeutic relationship, and to provide an integrated dynamic model for working with patients at each phase of treatment. This revised model acknowledges the complexity of the domain and encompasses the multiple tasks, functions, partners, and treatment phases involved. The utility of the revised theory is illustrated in application to understanding the sadomasochistic, omnipotent resistances of a female patient through the phases of her analysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66889/2/10.1177_00030651980460031301.pd

Genetic variants in CPA6 and PRPF31 are associated with variation in response to metformin in individuals with type 2 diabetes

Metformin is the first-line treatment for type 2 diabetes (T2D). Although widely prescribed, the glucose-lowering mechanism for metformin is incompletely understood. Here, we used a genome-wide association approach in a diverse group of individuals with T2D from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial to identify common and rare variants associated with HbA 1c response to metformin treatment and followed up these findings in four replication cohorts. Common variants in PRPF31 and CPA6 were associated with worse and better metformin response, respectively (P < 5 3 10 26 ), and meta-analysis in independent cohorts displayed similar associations with metformin response (P = 1.2 3 10 2 8 and P = 0.005, respectively). Previous studies have shown that PRPF31(+/2) knockout mice have increased total body fat (P = 1.78 3 10 26 ) and increased fasted circulating glucose (P = 5.73 3 10 26 ). Furthermore, rare variants in STAT3 associated with worse metformin response (q <0.1). STAT3 is a ubiquitously expressed pleiotropic transcriptional activator that participates in the regulation of metabolism and feeding behavior. Here, we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D

Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10 -6 ). Rare variant and gene expression changes were assessed using a false discovery rate approach. AKR7A3 and HSD17B13 were associated with lipid changes in white subjects (q < 0.2). Mice fed fenofibrate displayed reductions in Hsd17b13 gene expression (q < 0.1). Associations of variants in SMAD3, IPO11, and HSD17B13, with gene expression changes in mice indicate that transforming growth factor-beta (TGF-β) and NRF2 signaling pathways may influence fenofibrate effects on dyslipidemia in patients with T2D

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov: NCT01578239, EudraCT: 2011-005049-11

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening