Factors Associated With Ostomy Adjustment In People Living With An Intestinal Or Urinary Ostomy

poster abstractMore than 120,000 new ostomies, or surgically created openings through the abdomen for bowel or urinary elimination, are created annually in North America. Up to 80% of patients with a new ostomy experience ostomy-related complications that can interfere with adjusting to living with an ostomy and diminish quality of life. Short hospital stays and fragmented follow-up care make it difficult for people with new ostomies to adjust and find the support and resources they need. Little is known about factors that influence positive adjustment to a new ostomy. The purpose of this study was to explore demographic factors that may be associated with adjustment to living with an ostomy. Potentially eligible participants who had ostomy surgery in the past 24 months were identified from lists generated by wound, ostomy, and continence nurses in 5 hospitals affiliated with a major health system in Indiana. Introductory study letters were mailed to potentially eligible participants. Trained research assistants telephoned participants who did not call the office to decline in order to assess eligibility, explain the study, and answer questions. Quantitative and qualitative data were collected via telephone interviews from 203 participants and entered directly into the RedCap database. The Ostomy Adjustment Inventory-23 was used to assess adjustment to living with an ostomy. Data were analyzed using correlations, t-tests, and analyses of variance using the Statistical Package for the Social Sciences. Results indicated that participants with higher incomes had significantly better adjustment scores than those with lower incomes (p<.000). No other demographic variables were associated with ostomy adjustment. People with lower incomes may be at risk for poor adjustment after ostomy surgery. Additional support and education may be needed to enhance ostomy adjustment for people at risk. Future research is needed to develop and test the effectiveness of interventions to support ostomy adjustment

Clinical and molecular characterization of HER2 amplified-pancreatic cancer

&lt;p&gt;Background: Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.&lt;/p&gt; &lt;p&gt;Methods: HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).&lt;/p&gt; &lt;p&gt;Results: An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2- amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is &#62;22,000 per annum.&lt;/p&gt; &lt;p&gt;Conclusions: HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.&lt;/p&gt

Vicious walkers, friendly walkers and Young tableaux II: With a wall

We derive new results for the number of star and watermelon configurations of vicious walkers in the presence of an impenetrable wall by showing that these follow from standard results in the theory of Young tableaux, and combinatorial descriptions of symmetric functions. For the problem of $n$-friendly walkers, we derive exact asymptotics for the number of stars and watermelons both in the absence of a wall and in the presence of a wall.Comment: 35 pages, AmS-LaTeX; Definitions of n-friendly walkers clarified; the statement of Theorem 4 and its proof were correcte

Sexual minority youth and depressive symptoms or depressive disorder: A systematic review and meta-analysis of population-based studies

Objective: Research has suggested that sexual minority young people are more likely to have depressive symptoms or depressive disorder, but to date most studies in the field have relied on convenience-based samples. This study overcomes this limitation by systematically reviewing the literature from population-based studies and conducting a meta-analysis to identify whether depressive disorder and depressive symptoms are elevated in sexual minority youth. Method: A systematic review and meta-analysis were conducted and informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to determine if rates of depressive symptoms or depressive disorder differ for sexual minority youth, relative to heterosexual adolescents. MEDLINE, PsycINFO, EMBASE and ERIC databases were searched. Studies reporting depressive symptom data or the prevalence of depressive disorder in population-based samples of adolescents, that included sexual minority youth and heterosexual young people, were included in the review. A meta-analysis was conducted to examine differences between groups. Results: Twenty-three articles met the inclusion criteria. The proportion of sexual minority youth in the studies ranged from 2.3% to 12%. Sexual minority youth reported higher rates of depressive symptoms and depressive disorder (odds ratio = 2.94, pConclusions: There is robust evidence that rates of depressive disorder and depressive symptoms are elevated in sexual minority youth in comparison to heterosexual young people. Despite the elevated risk of depressive symptoms or depressive disorder for sexual minority youth, the treatment for this group of young people has received little attention

Characteristic maps for the Brauer algebra

The classical characteristic map associates symmetric functions to characters of the symmetric groups. There are two natural analogues of this map involving the Brauer algebra. The first of them relies on the action of the orthogonal or symplectic group on a space of tensors, while the second is provided by the action of this group on the symmetric algebra of the corresponding Lie algebra. We consider the second characteristic map both in the orthogonal and symplectic case, and calculate the images of central idempotents of the Brauer algebra in terms of the Schur polynomials. The calculation is based on the Okounkov--Olshanski binomial formula for the classical Lie groups. We also reproduce the hook dimension formulas for representations of the classical groups by deriving them from the properties of the primitive idempotents of the symmetric group and the Brauer algebra.Comment: 23 pages, minor changes made, a reference adde

Interpretability of radiomics models is improved when using feature group selection strategies for predicting molecular and clinical targets in clear-cell renal cell carcinoma: insights from the TRACERx Renal study

BACKGROUND: The aim of this work is to evaluate the performance of radiomics predictions for a range of molecular, genomic and clinical targets in patients with clear cell renal cell carcinoma (ccRCC) and demonstrate the impact of novel feature selection strategies and sub-segmentations on model interpretability. METHODS: Contrast-enhanced CT scans from the first 101 patients recruited to the TRACERx Renal Cancer study (NCT03226886) were used to derive radiomics classification models to predict 20 molecular, histopathology and clinical target variables. Manual 3D segmentation was used in conjunction with automatic sub-segmentation to generate radiomics features from the core, rim, high and low enhancing sub-regions, and the whole tumour. Comparisons were made between two classification model pipelines: a Conventional pipeline reflecting common radiomics practice, and a Proposed pipeline including two novel feature selection steps designed to improve model interpretability. For both pipelines nested cross-validation was used to estimate prediction performance and tune model hyper-parameters, and permutation testing was used to evaluate the statistical significance of the estimated performance measures. Further model robustness assessments were conducted by evaluating model variability across the cross-validation folds. RESULTS: Classification performance was significant (p  0.1. Five of these targets (necrosis on histology, presence of renal vein invasion, overall histological stage, linear evolutionary subtype and loss of 9p21.3 somatic alteration marker) had AUROC > 0.8. Models derived using the Proposed pipeline contained fewer feature groups than the Conventional pipeline, leading to more straightforward model interpretations without loss of performance. Sub-segmentations lead to improved performance and/or improved interpretability when predicting the presence of sarcomatoid differentiation and tumour stage. CONCLUSIONS: Use of the Proposed pipeline, which includes the novel feature selection methods, leads to more interpretable models without compromising prediction performance. TRIAL REGISTRATION: NCT03226886 (TRACERx Renal

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

The Effect of Chronic Endurance Exercise on Serum Levels of MOTS-c and Humanin in Professional Athletes

Background: Humanin and the mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) are mitochondrial encoded peptides involved in energy metabolism, cytoprotection, longevity, insulin sensitivity and their expression decrease with age. Levels of these molecules have been shown to respond to acute exercise, however little is known about their modulation under different chronic exercise conditions. In this study, we aim to compare levels of Humanin and MOTS-c in non-athletes vs professional (moderate and high endurance) athletes. Methods: Serum samples were collected from 30 non-athlete controls and 75 professional athletes (47 low/moderate endurance and 28 high endurance athletes). Levels of Humanin and MOTS-c were measured by the enzyme linked immunosorbent aaasy (ELISA) and linear models were generated to compare the effect of different levels of endurance exercise on these factors in different age groups. Spearman correlation was used to assess the correlation between these factors in athletes and non-athletes. Results: We showed that professional athletes had lower levels of MOTS-c and higher levels of Humanin than sedentary controls. Within the athletic groups, high endurance athletes had lower levels of Humanin than low/moderate endurance athletes of the same gender/age groups, whereas MOTS-c levels did not change between the subgroups. Humanin and MOTS-c levels were highly correlated in athletes, but not in sedentary controls. Conclusions: This pilot data suggests that serum levels of the mitochondrial proteins MOTS-c and Humanin change in response to chronic exercise with implications on energy metabolism and performance.This research was funded by the Qatar National Research Fund (QNRF), grant number NPRP13S-1230-190008, and Qatar University, grant number QUCG-BRC-21/22-1 (MAE).Scopu

Conceptual framework for the definition of preclinical and prodromal frontotemporal dementia

The presymptomatic stages of frontotemporal dementia (FTD) are still poorly defined and encompass a long accrual of progressive biological (preclinical) and then clinical (prodromal) changes, antedating the onset of dementia. The heterogeneity of clinical presentations and the different neuropathological phenotypes have prevented a prior clear description of either preclinical or prodromal FTD. Recent advances in therapeutic approaches, at least in monogenic disease, demand a proper definition of these predementia stages. It has become clear that a consensus lexicon is needed to comprehensively describe the stages that anticipate dementia. The goal of the present work is to review existing literature on the preclinical and prodromal phases of FTD, providing recommendations to address the unmet questions, therefore laying out a strategy for operationalizing and better characterizing these presymptomatic disease stages