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The human microbiome plays an important role in our health and identifying factors associated with microbiome composition provides insights into inherent disease mechanisms. By amplifying and sequencing the marker genes in high-throughput sequencing, with highly similar sequences binned together, we obtain operational taxonomic units (OTUs) profiles for each subject. Due to the high-dimensionality and nonnormality features of the OTUs, the measure of diversity is introduced as a summarization at the microbial community level, including the distance-based beta-diversity between individuals. Analyses of such between-subject attributes are not amenable to the predominant within-subject-based statistical paradigm, such as t-tests and linear regression. In this paper, we propose a new approach to model beta-diversity as a response within a regression setting by utilizing the functional response models (FRMs), a class of semiparametric models for between- as well as within-subject attributes. The new approach not only addresses limitations of current methods for beta-diversity with cross-sectional data, but also provides a premise for extending the approach to longitudinal and other clustered data in the future. The proposed approach is illustrated with both real and simulated data.

PurposeEndoxifen concentrations have been associated with breast cancer recurrence in tamoxifen-treated patients. However, tamoxifen itself and other metabolites also show antiestrogenic anti-tumor activity. Therefore, the aim of this study was to develop a comprehensive Antiestrogenic Activity Score (AAS), which accounts for concentration and antiestrogenic activity of tamoxifen and three metabolites. An association between the AAS and recurrence-free survival was investigated and compared to a previously published threshold for endoxifen concentrations of 5.97 ng/mL.Patients and methodsThe antiestrogenic activities of tamoxifen, (Z)-endoxifen, (Z)-4-hydroxytamoxifen, and N-desmethyltamoxifen were determined in a cell proliferation assay. The AAS was determined by calculating the sum of each metabolite concentration multiplied by an IC50 ratio, relative to tamoxifen. The AAS was calculated for 1370 patients with estrogen receptor alpha (ERα)-positive breast cancer. An association between AAS and recurrence was investigated using Cox regression and compared with the 5.97 ng/mL endoxifen threshold using concordance indices.ResultsAn AAS threshold of 1798 was associated with recurrence-free survival, hazard ratio (HR) 0.67 (95% confidence interval (CI) 0.47-0.96), bias corrected after bootstrap HR 0.69 (95% CI 0.48-0.99). The concordance indices for AAS and endoxifen did not significantly differ; however, using the AAS threshold instead of endoxifen led to different dose recommendations for 5.2% of the patients.ConclusionsEndoxifen concentrations can serve as a proxy for the antiestrogenic effect of tamoxifen and metabolites. However, for the aggregate effect of tamoxifen and three metabolites, defined by an integrative algorithm, a trend towards improving treatment is seen and moreover, is significantly associated with breast cancer recurrence.

Background: Depressive symptoms can lower adherence and change in dietary studies. Behavioral activation may reduce these effects. Purpose: This study aims to assess relationships among depressive symptoms on adherence and dietary change in the Women’s Healthy Eating and Living (WHEL) Study Methods: Secondary analyses from the WHEL Study, which achieved major dietary change in breast cancer survivors (N = 2817), were conducted. Logistic regressions were undertaken of baseline depressive symptoms (six-item Center for Epidemiologic Studies Depression Scale (CES-D)) with (1) completion of 1- and 4-year study assessments and (2) validated change in dietary behavior in the intervention group. Results: In the comparison group (vs. intervention), depressive symptoms lowered completion of dietary recalls and clinic visits [4 years: odds ratio (OR) = 2.0; 95 % confidence interval (CI) = 1.4–3.0]. The behaviorally oriented intervention achieved major change in those furthest from study targets, although changes were lower in those with depressive symptoms: fruit/vegetable (+37.2 %), fiber (+49.0 %), and fat (−22.4 %). Conclusions: Behavioral activation in dietary change interventions can overcome the impact of depressive symptoms.

Objective: Rapid eye movement (REM)-sleep behavior disorder (RBD) is often comorbid with Parkinson's disease (PD). The current study aimed to provide a detailed understanding of the impact of having RBD on multiple non-motor symptoms (NMS) in patients with PD. Methods: A total of 86 participants were evaluated for RBD and assessed for multiple NMS of PD. Principal component analysis was utilized to model multiple measures of NMS in PD, and a multivariate analysis of variance was used to assess the relationship between RBD and the multiple NMS measures. Seven NMS measures were assessed: cognition, quality of life, fatigue, sleepiness, overall sleep, mood, and overall NMS of PD. Results: Among the PD patients, 36 were classified as having RBD (objective polysomnography and subjective findings), 26 as not having RBD (neither objective nor subjective findings), and 24 as probably having RBD (either subjective or objective findings). RBD was a significant predictor of increased NMS in PD while controlling for dopaminergic therapy and age (p=0.01). The RBD group reported more NMS of depression (p=0.012), fatigue (p=0.036), overall sleep (p=0.018), and overall NMS (p=0.002). Conclusion: In PD, RBD is associated with more NMS, particularly increased depressive symptoms, sleep disturbances, and fatigue. More research is needed to assess whether PD patients with RBD represent a subtype of PD with different disease progression and phenomenological presentation. © 2014 Elsevier B.V.

Purpose: Sleep disturbance, fatigue and depression are common complaints in patients with cancer, and often contribute to worse quality of life (QoL). Circadian activity rhythms (CARs) are often disrupted in cancer patients. These symptoms worsen during treatment, but less is known about their long-term trajectory. Methods: Sixty-eight women with stage I-III breast cancer (BC) scheduled to receive ≥4 cycles of chemotherapy, and age-, ethnicity-, and education-matched normal, cancer-free controls (NC) participated. Sleep was measured with actigraphy (nocturnal total sleep time [nocturnal TST] and daytime total nap time [NAPTIME]) and with the Pittsburgh Sleep Quality Index (PSQI); fatigue with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF); depression with the Center of Epidemiological Studies-Depression (CES-D). CARs were derived from actigraphy. Several measures of QoL were administered. Data were collected at three time points: before (baseline), end of cycle 4 (cycle 4), and 1 year post-chemotherapy (1 year). Results: Compared to NC, BC had longer NAPTIME, worse sleep quality, more fatigue, more depressive symptoms, more disrupted CARs, and worse QoL at baseline (all p values

The wavelengths and rates of single- and double-electron transitions leading to the emission of a single photon between 2s3s and nsn'p (n = 1, 2 and n' = 2-4) groups in He-like ions with empty K shell have been studied for 15 ions in the range 13 [less than or equal to] Z [less than or equal to] 54 using fully relativistic multi-configuration Dirac-Fock wavefunctions in the active space approximation. The complete relaxation of atomic orbitals and most important configuration interaction effects have been taken into account. The variations in the admixture of the correlation functions coupled with Breit interaction responsible for the sudden changes in the line intensities of certain transitions from 2s3s have been discussed in detail. The radiative rates of the electric dipole transitions have been evaluated as accurately as possible by taking into account all the non-negligible contributions to the X-ray rates. The Auger rates have been calculated using a scaling procedure on the already existing relativistic radial matrix elements for an initial K hole atom. The present results are compared with other available theoretical data. The computed data can be conveniently used in the analysis of experimental spectra and in the measurements of X-ray fluorescence yields for the doubly excited states under study. Key words: He-like ions, relativistic correlation, Breit interaction, X-ray and Auger rates, fluorescence yields. Nous utilisons l'approximation dans l'espace actif des fonctions d'onde de Dirac-Fock multi-configurationnelles et pleinement relativistes, pour etudier les longueurs d'onde et les taux de transitions aun et deux electrons, menant a remission d'un seul photon entre les groupes 2s3s et nsn'p (n = 1, 2 and n' = 2-4), dans des ions de type He avec une couche K vide, pour 15 ions dans le domaine 13 [less than or equal to] Z [less than or equal to] 54. Nous tenons compte de la relaxation complete des orbitales atomiques et, plus important encore, de l'effet d'interaction entre les configurations. Nous discutons en detail les variations du melange des fonctions de correlation couple avec l'interaction de Breit qui est responsable pour les changements soudains dans les intensites de raie dans certaines transitions a partir de 2s3s. Les taux radiatifs des transitions dipolaires sont evalues avec autant de precision que possible, en tenant compte de toutes les contributions non negligeables aux taux de rayon X. Les taux Auger sont calcules en utilisant une procedure d'echelle sur les elements de matrice radiaux relativistes deja existants pour un atome initial K. Nos resultats sont compares avec d'autres donnees theoriques trouvees dans la litterature. Les donnees calculees peuvent etre utilisees a profit dans l'analyse de spectres experimentaux et dans les mesures de rendement de fluorescence X pour les etats doublement excites etudies. [Traduit par la Redaction] Mots-cles: ions de type He, correlation relativiste, de Breit, taux X et Auger, rendement de fluorescence., 1. Introduction High resolution resonance lines in the X-ray spectra of H-like and He-like ions and the associated satellite lines from doubly excited configurations provide valuable information on the plasma [...]

[beta]-catenins are conserved transcription factors regulated posttranslationally by Wnt signaling, bar-1 encodes a Caenorhabditis elegans [beta]-catenin acting in multiple Wnt-mediated processes, including cell fate specification by vulval precursor cells (VPCs) and migration of the [Q.sub.L] neuroblast progeny. We took two approaches to extend our knowledge of bar-1 function. First, we undertook a bar-1 promoter analysis using transcriptional GFP reporter fusions and found that bar-1 expression is regulated in specific cells at the transcriptional level. We identified promoter elements necessary for bar-1 expression in several cell types, including a 321-bp element sufficient for expression in ventral cord neurons (VCNs) and a 1.1-kb element sufficient for expression in the developing vulva and adult seam cells. Expression of bar-1 from the 321-bp element rescued the Uncoordinated (Unc) phenotype of bar-1 mutants, but not the vulval phenotype, suggesting that a Wnt pathway may act in ventral cord neurons to mediate proper locomotion. By comparison of the 1.1-kb element to homologous sequences from Caenorhabditis briggsae, we identified evolutionarily conserved sequences necessary for expression in vulval or seam cells. Second, we analyzed 24 mutations in bar-1 and identified several residues required for BAR-1 activity in C. elegans. By phylogenetic comparison, we found that most of these residues are conserved and may identify amino acids necessary for [beta]-catenin function in all species. Keywords: C. elegans; Vulva; Bar-1; Wnt; [beta]-catenin; Promoter; Transcription; Signaling

Aims: The purpose of this study is to explore the perceptions and practices of diabetes management through focus group discussions (FGDs) among adults with diabetes in rural Tamil Nadu. Materials and Methods: A qualitative study was conducted among individuals with diabetes who were part of the Telemedicine pRoject for screENing Diabetes and its complications in rural Tamil Nadu (TREND). A total of 16 FGDs were conducted using a semi-structured FGD guide that elicited perceptions of the different aspects of diabetes management and knowledge about diabetes prevention. The sample size was based on the attainment of thematic saturation. All FGDs were audio-recorded and transcribed verbatim. The textual data was then coded into meaning units and grouped into themes. Data were analyzed using NVIVO software version 10.0. Results: There were varied responses with respect to diet, medication adherence, regularity of follow-up, knowledge about diabetes, and diabetes prevention. Most participants had limited knowledge of the disease and did not have regular hospital visits. Several participants were unable to adhere to the diet prescribed by healthcare providers, as they lived alone or were dependent on someone in the family for dietary needs. Most participants were unaware that diabetes could be prevented. Some participants were interested in serving as “Diabetes ambassadors” to educate rural societies about diabetes. Conclusions: Understanding the perceptions and practices about diabetes management and prevention strategies could help primary healthcare workers effectively treat, manage, and prevent diabetes in underserved rural populations.