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After the rapid increase of the American divorce rate in the late 20th century, one of the most conspicuous efforts of the marriage movement in the 1990s that was used to increase marital stability was the legislation of the covenant marriage license, a more restricted marriage license issued in three different states of the U.S. To investigate the marital life of newlywed covenant versus standard couples, a large‐scale 5‐year couple study was conducted between 1998 and 2003 in Louisiana. The present study uses this large‐sample, multiple‐wave, multiple‐group dyadic dataset to examine differences in co‐development and divorce rates in 297 covenant and 380 standard mixed‐sex couples using a multiple group growth curve modeling and survival analysis. We examined differences in marital trajectories between covenant and standard couples as well as between husbands and wives in each marital group. The results show (1) that the couples in both groups experienced, on average, declines in marital satisfaction, and such a decline was slower in covenant husbands than their wives as well as those in standard marriages, and (2) that co‐development in marital satisfaction was more prominent in standard marriages than in covenant marriages, meaning standard couple's marital satisfaction declined at a more similar rate than that of covenant couples. We provide possible explanations and discuss practical implications. [ABSTRACT FROM AUTHOR]

This article discusses the potential use of the MEK inhibitor trametinib as a treatment for hereditary haemorrhagic telangiectasia (HHT), a condition characterized by vascular malformations. The study presents a clinical case of a patient with HHT who experienced a reduction in nosebleeds and transfusion requirements after taking trametinib. The authors also provide RNA sequencing data from blood outgrowth endothelial cells (BOECs) derived from HHT patients, which suggest that MEK1 inhibition may be beneficial in reducing HHT-associated bleeding and anemia. Further research is needed to confirm these findings and optimize dosing regimens. [Extracted from the article]

In this review, we discuss the most commonly used models to analyze dyadic longitudinal data. We start the review with a definition of dyadic longitudinal data that allows relationship researchers to identify when these models might be appropriate. Then, we go on to describe the three major models commonly used when one has dyadic longitudinal data: the dyadic growth curve model (DGCM), the actor–partner interdependence model (APIM), and the common fate growth model (CFGM). We discuss when each model might be used and strengths and weaknesses of each model. We end with additional thoughts that focus on extensions to new methods being discussed in the literature, along with some of the challenges of collecting and analyzing dyadic longitudinal data that might be helpful for future dyadic researchers. [ABSTRACT FROM AUTHOR]

Covenant marriage is a legally distinct marriage license available in Arizona, Louisiana, and Arkansas in the United States. This study revisited one of the largest longitudinal dyadic studies on covenant versus standard newlywed couples. Using this dataset of 677 different‐sex couples, we explored whether being in a covenant marriage could predict how marital satisfaction developed over the first five marital years. We applied the Growth Mixture Modeling (GMM) method to identify groups that differed in their initial marital satisfaction and trajectory. The results revealed three different trajectory groups—one group showing high and stable marital satisfaction, which we named High Stable, and two groups showing declines in marital satisfaction, one being medium and the other one being low in satisfaction at the beginning of the marriage, and we named them Medium Declining and Low Declining respectively. Spouses with lower initial marital satisfaction experienced a faster decline and suffered the highest divorce rate. Actor‐Partner Interdependence Model (APIM) analysis revealed that one's group membership was predicted by their partner's membership, suggesting a mutual influence on marital development. Being in a covenant marriage was able to predict husbands' membership as covenant husbands were found to be more likely in the high stable group. [ABSTRACT FROM AUTHOR]

Examining associations between therapists' perceptions of therapy sessions and client‐reported outcomes in naturalistic settings (real‐life therapy settings) can provide valuable guidance for the assessment, treatment, and monitoring of clients. This study included data of 1334 sessions from 127 clients (86 individual and 41 couple cases) and 15 therapists, collected at a therapy training center. Clients reported their personal functioning and individual symptoms before each session. Therapists rated clients' participation, receptivity, session progress, goal progress, and therapeutic alliance at the end of each therapy session. Multilevel Structural Equation Modeling analyses revealed that therapist‐rated client participation and goal progress predicted better personal functioning, beyond clients' previous personal functioning scores. In contrast, none of therapist‐rated session variables predicted clients' individual symptoms, beyond previous symptom scores. Power analyses suggested sufficient statistical power to detect small effect sizes. Findings of the current study have clinical implications for treatment planning and progress monitoring. [ABSTRACT FROM AUTHOR]

The plant common symbiosis signalling (SYM) pathway has shared function between interactions with rhizobia and arbuscular mycorrhizal fungi, the two most important symbiotic interactions between plants and microorganisms that are crucial in plant and agricultural yields. Here, we determine the role of the plant SYM pathway in the structure and abundance of the microbiota in the model legume Medicago truncatula and whether this is controlled by the nitrogen or phosphorus status of the plant. We show that SYM mutants (dmi3) differ substantially from the wild type (WT) in the absolute abundance of the root microbiota, especially under nitrogen limitation. Changes in the structure of the microbiota were less pronounced and depended on both plant genotype and nutrient status. Thus, the SYM pathway has a major impact on microbial abundance in M. truncatula and also subtly alters the composition of the microbiota. [ABSTRACT FROM AUTHOR]

Objective: The goal of the present study was to determine the psychometric properties of an extended inventory that assesses the multiple facets of divorce initiation drawn from the existing research, the Revised Divorce Initiation Inventory (DII‐R). Background: Previous research indicates the role of each partner in the initiation of divorce has relevant implications for emotional and psychological well‐being after the divorce. Much of this research was conducted with a single‐item, categorical assessment of initiator status (e.g., who initiated the divorce?). However, recent studies highlight the complexity of divorce initiation as a multidimensional concept. Method: A confirmatory factor analysis (CFA) was conducted with a sample of 408 divorced individuals. Analyses to explore measurement invariance between men and women and construct validity were also conducted. Results: Findings indicated a four‐factor model (i.e., Legal, Separation, Desire, Responsibility) of 12 items was a good fit to the data. Factor loadings and intercepts were equal across groups. Conclusion: Divorce initiation is a multifaceted construct that includes dimensions related to separation, legal, desire, and responsibility that should not be measured with a single‐item assessment. Implications: The DII‐R supports the comprehensive synthesis of ongoing divorce initiation research that may be used to inform clinical practice to intervene in specific areas shown to affect the decision to divorce. [ABSTRACT FROM AUTHOR]

Objective: We provide details on how relationship researchers can use Monte Carlo simulation for power estimation and sample size determination for the simple and the mediation Actor–Partner Interdependence Model (APIM). In addition to power estimates for specific sample sizes, we show how the sample size for each effect can be determined. Background: Researchers designing a study commonly want to know what sample size is required to detect a specific effect or in the case after data collection is completed what the power is for a specific effect. Method: The solution we present asks for the correlations among the variables and allows for the specification of skewness and kurtosis and the incorporation of missing data. For the mediation APIM, power is estimated for the direct effects, indirect effects, and total effects. Results: The illustrations demonstrate that indistinguishable members require sample sizes that are about half of the sample sizes required for distinguishable members and that skewed data tend to require larger sample sizes. The illustration of the mediation APIM reveals that it is not uncommon that some of the simple indirect effects are significant, but none of the total indirect effects and none of the total effects are. Conclusion: Monte Carlo simulation provides an easy‐to‐use and flexible solution to determine power and sample sizes for the simple and mediation APIM for distinguishable and indistinguishable members. Implications: Recommendations are made for dyadic studies with small sample sizes and studies using the mediation APIM. [ABSTRACT FROM AUTHOR]

Objective: This study used longitudinal data from a sample of low‐income mothers and their children to examine how informal support and obligation, or informal networks, contribute to children's behavior. We also tested the potential mediating role of maternal parenting stress. Background: Many studies document the importance of informal support for maternal stress and child behavior to offset the negative impact of poverty for low‐income families. Evidence suggests the importance of also considering the obligations that such informal support access may impart. Method: Using data from the Welfare, Children, Families Study, a longitudinal study of diverse, low‐income, urban mothers in three cities (n = 2142), we used a parallel process latent growth curve model approach to examine how informal support and obligation contributed to maternal stress and child behavior. Results: Models indicated that mothers with healthy safety nets, including informal support and manageable obligations, had children with fewer behavior problems, and parenting stress partially accounted for the positive effects. Conclusions: Results highlight the importance of considering reciprocity norms among low‐income mothers; one‐sided support or obligation can be problematic for both maternal stress and child behavior problems. Implications: Results suggest the merit of empirically supported interventions to teach relationship skills and facilitate healthy relationships among low‐income mothers. [ABSTRACT FROM AUTHOR]

Copyright of Family Process is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: The authors performed a meta‐analysis to better quantify the benefit of maintenance poly(ADP‐ribose) polymerase inhibitor (PARPi) therapy to inform practice in platinum‐sensitive, recurrent, high‐grade ovarian cancer for patient subsets with the following characteristics: germline BRCA mutation (gBRCAm), somatic BRCA mutation (sBRCAm), wild‐type BRCA but homologous recombinant‐deficient (HRD), homologous recombinant‐proficient (HRP), and baseline clinical prognostic characteristics. METHODS: Randomized trials comparing a PARPi versus placebo as maintenance treatment were identified from electronic databases. Treatment estimates of progression‐free survival were pooled across trials using the inverse variance weighted method. RESULTS: Four trials included 972 patients who received a PARPi (olaparib, 31%; niraparib, 35%; or rucaparib, 34%) and 530 patients who received placebo. For patients who had germline BRCA1 mutation (gBRCAm1) (N = 471), the hazard ratio (HR) was 0.29 (95% CI, 0.23‐0.37); for those who had germline BRCA2 mutation (gBRCAm2) (N = 236), the HR was 0.26 (95% CI, 0.17‐0.39); and, for those who had sBRCAm (N = 123), the HR was 0.22 (95% CI, 0.12‐0.41). The treatment effect was similar between the gBRCAm and sBRCAm subsets (P =.48). In patients who had wild‐type BRCA HRD tumors (excluding sBRCAm; N = 309), the HR was 0.41 (95% CI, 0.31‐0.56); and, in those who had wild‐type BRCA HRP tumors (N = 346), the HR was 0.64 (95% CI, 0.49‐0.83). The relative treatment effect was greater for the BRCAm versus HRD (P =.03), BRCAm versus HRP (P <.00001), and HRD versus HRP (P <.00001) subsets. There was no difference in benefit based on age, response after recent chemotherapy, and prior bevacizumab. CONCLUSIONS: In platinum‐sensitive, recurrent, high‐grade ovarian cancer, maintenance PARPi improves progression‐free survival for all patient subsets. PARPi therapy has a similar magnitude of benefit for sBRCAm and gBRCAm. Although patients with BRCAm derive the greatest benefit, the absence of a BRCAm or HRD could not be used to exclude patients from maintenance PARPi therapy. BRCA mutation status is able to predict for the magnitude of PARP inhibitor benefit in platinum‐sensitive recurrent high‐grade ovarian tumor. However, the absence of a BRCA mutation or homologous recombinant deficiency in high‐grade ovarian tumor cannot be used to exclude patients from such therapy. [ABSTRACT FROM AUTHOR]

Copyright of Family Process is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The therapeutic alliance is central to couples' therapy success. The current study examined associations between couples' initial agreement and causal attributions of the presenting problem and changes in the therapeutic alliance. To test study hypotheses, 85 couples were recruited from a university training clinic focused on couple and family therapy. Couples completed an intake questionnaire concerning their attribution of the presenting problem, either as systemic or individual, and therapeutic alliance was assessed at the end of sessions 2-8. A dyadic multilevel model revealed that a disagreement in the couple's attributions of the problem (with one viewing it as systemic, the other as individual) was associated with a larger initial discrepancy in the couple's therapeutic alliance, as well as a decline in the discrepancy over time. Findings were discussed in the context of systemic family theory, with implications for improving assessment, treatment, and psychoeducation aimed toward couples in distress. [ABSTRACT FROM AUTHOR]

Background: Extensive literature has investigated the role of serotonin (5‐HT) in the control of the central dopamine (DA) systems, and their dysfunction in the pathological conditions. 5‐HT stimulates the local DA release in striatal regions via activation of various receptors including serotonin receptor‐3 (5‐HT3). Several studies have related polymorphisms (SNPs) in the serotonin receptor‐3 (HTR3) genes to be associated with the pain modulation and endogenous pain suppression. A few studies suggested a functional role of 5ʹUTR SNP in the serotonergic receptor HTR3A gene (rs1062613) in the development of the chronic pain and Fibromyalgia syndrome (FMS) in particular. Here, we investigated the effect of a 5ʹUTR SNP in the serotonergic receptor HTR3A gene (rs1062613) on striatal dopamine D2/D3 receptor (DRD2) availability and reward‐associated DA release in response to unpredictable monetary rewards in 23 women with FMS and 17 age‐matched healthy female controls. Furthermore, we aimed to examine if SNP rs1062613 is associated with thermal pain and pain tolerance thresholds. Methods: We used PET and [11C]raclopride to assess the DRD2 availability. In the same participants we used the [11C]raclopride PET bolus‐plus‐infusion method to measure the [11C]raclopride receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition. DRD2 availability and ΔBP were assessed in MRI‐based striatal regions of interest. Thermal pain and pain tolerance thresholds were assessed outside the scanner. Results: The frequency of SNP rs1062613 genotype differed significantly between groups, indicating that CC homozygotes were more frequent in FMS patients (82.6%) than in healthy controls (41.3%). Our results showed a significant main effect of SNP rs1062613 on [11C]raclopride binding potential in the right caudate nucleus indicating a higher DRD2 receptor availability for CC‐genotype of this SNP. Furthermore, we found a significant group × SNP interaction on [11C]raclopride binding potential in the right putamen, indicating a higher DRD2 availability in T‐carriers compared to CC genotype of SNP rs1062613 in FMS patients, whereas this effect was not present in healthy controls. However, we did not find an influence of SNP rs1062613 on reward‐related DA release. In addition, there was no association between SNP rs1062613 and pain threshold or pain tolerance threshold in our data. Conclusion: These preliminary results indicate that SNP rs1062613 in the serotonergic receptor HTR3A gene possibly modulates the DRD2 receptor availability. [ABSTRACT FROM AUTHOR]

The current study examined dyadic reports of mother-adolescent relationship quality (RQ) as a mechanism by which emotional, physical, and sexual abuse affect posttraumatic stress symptoms (PTSS) over time from a family systems perspective. We used three waves of data from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN), including 321 mother-adolescent dyads observed when adolescents were approximately 12, 14, and 16 years old. We used an extended version of the actor-partner interdependence mediation model to analyze the effect of emotional, physical, and sexual abuse on adolescents' PTSS through dyadic reports of mother-adolescent RQ. Results yielded significant indirect effects between sexual and emotional abuse, but not physical abuse, and PTSS 4 years later through adolescent perceptions of RQ. Maternal perceptions of RQ were not directly associated with adolescents' PTSS; however, maternal perceptions of RQ positively contributed to future adolescent perceptions of RQ. Clinical implications are discussed. [ABSTRACT FROM AUTHOR]

This paper proposes a framework for dealing with the complexity of food systems for guiding implementation, monitoring and evaluation of Sustainable Development Goal number 2 ‘End hunger, achieve food security and improved nutrition and promote sustainable agriculture’. The framework combines a food systems approach with systems analysis and modelling techniques and helps identifying areas in need of further clarification for an effective post‐2015 development agenda. Furthermore, the paper explains how the proposed framework can be used in developing theory of transformations and in formulating indicators that control for dynamic complexity. The paper also emphasizes the importance of building comprehensive monitoring systems for this purpose. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Ferredoxin‐dependent bilin reductases (FDBRs) are a class of enzymes reducing the heme metabolite biliverdin IXα (BV) to form open‐chain tetrapyrroles used for light‐perception and light‐harvesting in photosynthetic organisms. Thus far, seven FDBR families have been identified, each catalysing a distinct reaction and either transferring two or four electrons from ferredoxin onto the substrate. The newest addition to the family is PcyX, originally identified from metagenomics data derived from phage. Phylogenetically, PcyA is the closest relative catalysing the reduction of BV to phycocyanobilin. PcyX, however, converts the same substrate to phycoerythrobilin, resembling the reaction catalysed by cyanophage PebS. Within this study, we aimed at understanding the evolution of catalytic activities within FDBRs using PcyX as an example. Additional members of the PcyX clade and a remote member of the PcyA family were investigated to gain insights into catalysis. Biochemical data in combination with the PcyX crystal structure revealed that a conserved aspartate‐histidine pair is critical for activity. Interestingly, the same residues are part of a catalytic Asp‐His‐Glu triad in PcyA, including an additional Glu. While this Glu residue is replaced by Asp in PcyX, it is not involved in catalysis. Substitution back to a Glu failed to convert PcyX to a PcyA. Therefore, the change in regiospecificity is not only caused by individual catalytic amino acid residues. Rather the combination of the architecture of the active site with the positioning of the substrate triggers specific proton transfer yielding the individual phycobilin products. Enzymes: Suggested EC number for PcyX: 1.3.7.6 Databases: The PcyX X‐ray structure was deposited in the PDB with the accession code 5OWG. [ABSTRACT FROM AUTHOR]

Background: The ICON6 trial showed that cediranib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, improved clinical outcomes for patients with platinum-sensitive relapsed ovarian cancer when it was used with chemotherapy and was continued as maintenance therapy. This study describes health-related quality of life (QOL) during the first year of treatment.Methods: Four hundred fifty-six women were randomly allocated to receive standard chemotherapy only, chemotherapy with concurrent cediranib, or chemotherapy with cediranib administered concurrently and continued as maintenance. Patients completed QOL questionnaires until disease progression every 3 weeks during chemotherapy and then every 6 weeks to 1 year. Patients alive with disease progression completed a QOL form 1 year after randomization. The primary QOL endpoint was the global score from the Quality of Life Questionnaire Core 30 (of the European Organization for Research and Treatment of Cancer) at 1 year, with the standard chemotherapy group compared with the concurrent-maintenance cediranib group.Results: The rate of questionnaire compliance was 90% at the baseline and 76% at 1 year and was similar across the 3 groups. The mean global QOL score at 1 year was 62.6 points for the standard chemotherapy group and 68.7 points for the concurrent-maintenance group (+4.5; 95% confidence interval, -2.0 to 11.0; P = .18). Sensitivity analyses suggested that this finding was robust to the effect of missing data, and the improvement became statistically significant after adjustments for self-reported diarrhea.Conclusions: The 6th study by the International Collaboration in Ovarian Neoplasm (ICON6) showed a significant improvement in progression-free survival with cediranib as concurrent and maintenance therapy. No QOL detriment with cediranib was found 1 year after treatment was commenced. The maintenance of QOL along with prolonged cancer control suggests that cediranib has a valuable role in the treatment of relapsed ovarian cancer. Cancer 2017;123:2752-61. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. [ABSTRACT FROM AUTHOR]

Data from groups often have a multimember multigroup ( MMMG) structure. Examples are two-parent families with a female or male child (three members, two groups), two same-gender and opposite-gender peers of different status (two members, four groups), or gay, lesbian, and heterosexual couples (two members, three groups). To analyze such data, a framework called MMMG actor-partner interdependence model ( MMMG APIM) is presented considering group composition. Three models are discussed in detail: the three-member two-group APIM, the two-member four-group APIM, and the two-member three-group APIM. Structural equation modeling and cross-sectional and longitudinal data are used to illustrate the approach. To ease the interpretation of APIM findings, a proposal of a general classification scheme is made. [ABSTRACT FROM AUTHOR]

The pink open-chain tetrapyrrole pigment phycoerythrobilin (PEB) is employed by marine cyanobacteria, red algae and cryptophytes as a light-harvesting chromophore in phycobiliproteins. Genes encoding biosynthesis proteins for PEB have also been discovered in cyanophages, viruses that infect cyanobacteria, and mimic host pigment biosynthesis with the exception of PebS which combines the enzymatic activities of two host enzymes. In this study, we have identified novel members of the PEB biosynthetic enzyme families, heme oxygenases and ferredoxin-dependent bilin reductases. Encoding genes were found in metagenomic datasets and could be traced back to bacteriophage but not cyanophage origin. While the heme oxygenase exhibited standard activity, a new bilin reductase with highest homology to the teal pigment producing enzyme PcyA revealed PEB biosynthetic activity. Although PcyX possesses PebS-like activity both enzymes share only 9% sequence identity and likely catalyze the reaction via two independent mechanisms. Our data point towards the presence of phycobilin biosynthetic genes in phages that probably infect alphaproteobacteria and, therefore, further support a role of phycobilins outside oxygenic phototrophs. [ABSTRACT FROM AUTHOR]

Background: Maintenance treatment with the oral poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor olaparib (Lynparza) in Study 19 (study number, D0810C00019; ClinicalTrials.gov identifier, NCT00753545) significantly improved progression-free survival in comparison with a placebo for patients with platinum-sensitive, relapsed serous ovarian cancer with a BRCA1/2 mutation (BRCAm), but an interim analysis revealed no statistically significant overall survival (OS) benefit. However, 23% of the patients receiving the placebo switched to a PARP inhibitor after progression. To investigate whether this had a confounding effect on OS, this article reports an exploratory post hoc analysis that excluded all patients from sites where 1 or more placebo patients received postprogression PARP inhibitor treatment.Methods: In Study 19, 136 of the 265 patients receiving olaparib or a placebo had a BRCAm. Sixteen patients treated at 11 of the 82 investigational sites received a PARP inhibitor after progression; these sites were excluded from this analysis, and 97 BRCAm patients at 50 sites were included. OS was assessed with a Cox proportional hazards model analogous to the primary study analysis. A supporting rank-preserving structural failure time (RPSFT) model analysis was undertaken for all 136 BRCAm patients.Results: The OS hazard ratio (HR) was 0.52 (95% confidence interval [CI], 0.28-0.97) for the 97 BRCAm patients, whereas for the interim OS analysis with all 136 BRCAm patients, it was 0.73 (95% CI, 0.45-1.17). The supportive RPSFT analysis HR was approximately 0.66.Conclusions: The numerical improvement in the OS HR suggests that in Study 19, postprogression PARP inhibitor treatment had a confounding influence on the interim OS analysis for BRCAm patients. There is a degree of uncertainty due to the small sample size and the lack of data maturity. Cancer 2016;122:1844-52. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Tetrahydrobiopterin (BH) is an essential cofactor for the aromatic amino acid hydroxylases, alkylglycerol monooxygenase, and nitric oxide synthases (NOS). Inborn errors of BH metabolism lead to severe insufficiency of brain monoamine neurotransmitters while augmentation of BH by supplementation or stimulation of its biosynthesis is thought to ameliorate endothelial NOS (eNOS) dysfunction, to protect from (cardio-) vascular disease and/or prevent obesity and development of the metabolic syndrome. We have previously reported that homozygous knock-out mice for the 6-pyruvolytetrahydropterin synthase (PTPS; Pts-ko/ko) mice with no BH biosynthesis die after birth. Here we generated a Pts-knock-in ( Pts-ki) allele expressing the murine PTPS-p.Arg15Cys with low residual activity (15 % of wild-type in vitro) and investigated homozygous ( Pts-ki/ki) and compound heterozygous ( Pts-ki/ko) mutants. All mice showed normal viability and depending on the severity of the Pts alleles exhibited up to 90 % reduction of PTPS activity concomitant with neopterin elevation and mild reduction of total biopterin while blood L-phenylalanine and brain monoamine neurotransmitters were unaffected. Yet, adult mutant mice with compromised PTPS activity (i.e., Pts-ki/ko, Pts-ki/ki or Pts-ko/wt) had increased body weight and elevated intra-abdominal fat. Comprehensive phenotyping of Pts-ki/ki mice revealed alterations in energy metabolism with proportionally higher fat content but lower lean mass, and increased blood glucose and cholesterol. Transcriptome analysis indicated changes in glucose and lipid metabolism. Furthermore, differentially expressed genes associated with obesity, weight loss, hepatic steatosis, and insulin sensitivity were consistent with the observed phenotypic alterations. We conclude that reduced PTPS activity concomitant with mildly compromised BH-biosynthesis leads to abnormal body fat distribution and abdominal obesity at least in mice. This study associates a novel single gene mutation with monogenic forms of obesity. [ABSTRACT FROM AUTHOR]

The thymic epithelium forms specialized niches to enable thymocyte differentiation. While the common epithelial progenitor of medullary and cortical thymic epithelial cells (mTECs and cTECs) is well defined, early stages of mTEC lineage specification have remained elusive. Here, we utilized in vivo targeting of mTECs to resolve their differentiation pathways and to determine whether mTEC progenitors participate in thymocyte education. We found that mTECs descend from a lineage committed, podoplanin (PDPN)-expressing progenitor located at the cortico-medullary junction. PDPN+ junctional TECs (jTECs) represent a distinct TEC population that builds the thymic medulla, but only partially supports negative selection and thymocyte differentiation. Moreover, conditional gene targeting revealed that abrogation of alternative NF-κB pathway signaling in the jTEC stage completely blocked mTEC development. Taken together, this study identifies jTECs as lineage-committed mTEC progenitors and shows that NF-κB-dependent progression of jTECs to mTECs is critical to secure central tolerance. [ABSTRACT FROM AUTHOR]

Ovarian cancer patients are usually diagnosed at an advanced stage, experience recurrence after platinum-based chemotherapy, and eventually develop resistance to chemotherapy. Overall survival (OS), which has improved in recent years as more active treatments have been incorporated into patient care, is regarded as the most clinically relevant endpoint in ovarian cancer trials. However, although there remains a significant need for new treatments that prolong OS further without compromising quality of life, it has become increasingly difficult to detect an OS benefit for investigational treatments because of the use of multiple lines of chemotherapy to treat ovarian cancer. Progression-free survival (PFS), which measures the time to disease progression or death, is unaffected by postprogression therapies but does not evaluate the long-term impact of investigational treatments on tumor biology and responses to future therapies. Recent clinical trials of targeted agents in relapsed ovarian cancer have shown improvements in PFS but not OS, and this is possibly reflective of the long postprogression survival (PPS) period associated with this disease. Intermediate endpoints such as the time to second disease progression or death and the time to second subsequent therapy or death may provide supportive evidence for clinically meaningful PFS improvements and may be used to determine whether these improvements persist beyond the first disease progression and throughout subsequent lines of therapy. For clinical trials that have settings with a long PPS duration and/or involve multiple rounds of postprogression therapy, a primary endpoint of PFS supported by intermediate clinical endpoints and OS may provide a more comprehensive approach for evaluating efficacy. Cancer 2015;121:1737-1746. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Potential moderators of effects in the actor-partner interdependence model ( APIM) include variables that vary within dyads, between dyads, or both between and within dyads (i.e., mixed moderators). Another factor in the moderation of the APIM is whether dyads are indistinguishable (e.g., same-sex friendship pairs) or distinguishable (e.g., heterosexual couples). For each possibility, what are the potential moderator effects (up to 8), how they might be estimated and tested, and how they can be interpreted are discussed. Submodels are also presented, based on patterns of moderation of the actor and partner effects, which are statistically simpler, more conceptually meaningful, and more powerful in testing moderator effects. Example analyses illustrate the recommended steps involved in an APIM moderation analysis. [ABSTRACT FROM AUTHOR]

In this paper regression is discussed as a process that can occur both in neurosis and in personality disorder. Regression is contrasted with the phenomenon of stagnation, which is a state characteristic of personality disorder. The aetiology of both regression and stagnation is based on Fordham's theory of deintegration. His concept of the defences of the primal self explains the phenomenon of stagnation. Clinical material is presented. Emphasis is laid on the difference between the treatment of neurotic and stagnated patients. The significance of specific archetypal images that arise in the analysis of stagnated patients is stressed. [ABSTRACT FROM AUTHOR]

Focuses on the pathological sexuality and paucity of symbolization in narcissistic disorder. Hindrance to the ego formation; Accounts on references in psychoanalytic literature related to psycho-sexual development; Discussion of some aspects of pathological sexual development in narcissistic disorder.

Discusses the treatment for narcissistic disorder. Nature of the disorder; Author's view that the syndrome differs from other personality disorders; Main clinical manifestations of narcissistic disorder; Need for the analyst to always greet the patient with warmth and openness, irrespective of what had occurred in the preceding session.

Discusses the hypothesis about the roots of narcissistic personality disorder. Origins and nature of the disorder; Nexus of early infantile defense structures which leads to narcissistic disorder; Author's clinical work with two patients who showed many features of the disorder; Factors that influenced the author's understanding of the origin of the patients' psychopathology, including Jung's theory of archetypes; Several definitions of narcissistic disorder; Deficiencies in the patients' capacity to love, chronic dissatisfaction about themselves, and exploitativeness and ruthlessness towards others.

Copyright of Swiss Political Science Review is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ABSTRACT This paper studied the development of no-tillage by combining concepts of co-creation of knowledge and actor-network theory. Reconstructing the process of no-tillage development in Switzerland has made it possible to show that no-tillage development may be regarded as a dynamic process of co-creation of innovation, where human and non-human actors are building networks by reciprocally transforming and translating each other and the relations between them. This conceptualisation reveals that spread of no-tillage requires fundamental transformations within the network of conventional plough-tillage agriculture, including institutional arrangements, farm equipment, work organisation, concepts of agriculture and personal and professional identities. Against this background, the limited spread of no-tillage-despite its economic and ecological advantages-can be explained by the fact that the required transformations are too radical for many agricultural actors. This conceptualisation also implies that policy interventions are not understood as top down measures that intend to induce one-to-one direct causal chains between knowledge and action of farmers, but as mediators in a complex process of reciprocal translations between farmers, experts and scientists, as well as many non-human actors. We conclude that investigating processes of co-creation of knowledge from the perspective of actor-network theory is a promising complement to hermeneutic approaches to co-creation of knowledge such as social learning. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article discusses an analysis of the one year of soil erosion damage mapping done in three study areas in Switzerland that considers the spatial aspects of soil erosion and off-site impacts downslope. The three study areas were chosen to cover important differences in Swiss agriculture with a total of about 1,000 hectares of arable farmland were mapped made up of 780 arable plots. It concludes that rill mapping indicated that soil erosion is a drainage problem at the watershed level whose mitigation will involve farmers and the communities.

The association between daily stress outside and inside of the relationship and marital functioning in the form of communication in conflict situations and marital quality was examined. We hypothesized that relationship stress mediates the association between external stress and marital functioning at the individual level, and that the association between relationship stress and marital quality is partially mediated by communication at the dyadic level. Using the Actor-Partner Interdependence and Common Fate Model, the results of 345 couples supported our hypotheses and revealed that a person's relationship stress is more strongly related with one's own external stress than with the partner's external stress. The findings indicate that both low relationship stress and a high level of positive communication are important in relationships. [ABSTRACT FROM AUTHOR]

Using data from 198 couples, this study examines whether associations between stress occurring outside of the dyad and key indicators of relationship functioning are mediated by stress arising within the dyad. Findings suggest that relationship satisfaction and sexual activity are governed by hassles and problems experienced within the dyad that are in turn related to stress arising outside the dyad. Associations between external stress and relationship functioning are stronger for daily hassles than for critical life events. Higher levels of daily stress predicted less sexual activity for maritally dissatisfied women and more sexual activity for maritally dissatisfied men. Self-reports of stress covaried with self-reported indexes of satisfaction and sexuality, suggesting that contextual influences are broadly influential in intimate relationships. [ABSTRACT FROM AUTHOR]

Paediatric urology can uncover the most complicated cases that require careful attention to management details. Authors from the UK present a retrospective review of their experience of children who had undergone both renal transplantation and bladder augmentation. They recommend that the bladder be reconstructed before renal transplantation, as it might protect the transplanted kidney, and specifically the transplanted ureter. OBJECTIVE To identify whether the order of performing transplant and bladder reconstruction operations in children who need both operations affects outcome of either operation. PATIENTS AND METHODS A retrospective case note review was performed of children identified from our database, who had undergone both renal transplantation and bladder augmentation between 1990 and 2005. RESULTS In all, 18 renal transplants (eight live-related) were performed in 16 children with 10 transplants done after bladder augmentation and eight transplants done before augmentation. The median age at transplantation was 7.5 years and at augmentation was 7.0 years. The median interval between the operations was 33.5 months and the median follow-up was 58.4 months after transplantation. Outcomes were compared between the two groups of patients: those who received their transplantation before bladder augmentation, and those who were transplanted after bladder augmentation. There was no difference between these groups in: the pre- transplant estimated glomerular filtration rate, inpatient stay after transplantation or after augmentation, and incidence of urinary tract infection in the 3 months after renal transplantation or after bladder augmentation. There was no statistical difference in renal allograft loss with one graft failure in the group who were augmented first, and four graft failures in the group who were transplanted first. However, it is of note that the single graft failure in the patient augmented first was due to renal artery thrombosis on the first day related to a double arterial anastomosis, whilst in the other group, three of the graft failures were in transplants that had initially been drained by ureterostomy. Three patients in the group transplanted first developed significant ureteric pathology, of which one developed graft failure. CONCLUSION Bladder reconstruction can be performed safely before transplantation; it does not increase complications and might better protect the renal graft and specifically the transplant ureter. [ABSTRACT FROM AUTHOR]

The synaptic serine protease neurotrypsin is thought to be important for adaptive synaptic processes required for cognitive functions, because humans deficient in neurotrypsin suffer from severe mental retardation. In the present study, we describe the biochemical characterization of neurotrypsin and its so far unique substrate agrin. In cell culture experiment as well as in neurotrypsin-deficient mice, we showed that agrin cleavage depends on neurotrypsin and occurs at two conserved sites. Neurotrypsin and agrin were expressed recombinantly, purified, and assayed in vitro. A catalytic efficiency of 1.3 x 104 M-1⋅ s-1 was determined. Neurotrypsin activity was shown to depend on calcium with an optimal activity in the pH range of 7-8.5. Mutagenesis analysis of the amino acids flanking the scissile bonds showed that cleavage is highly specific due to the unique substrate recognition pocket of neurotrypsin at the active site. The C-terminal agrin fragment released after cleavage has recently been identified as an inactivating ligand of the Na+/ K+-ATPase at CNS synapses, and its binding has been demonstrated to regulate presynaptic excitability. Therefore, dysregulation of agrin processing is a good candidate for a pathogenetic mechanism underlying mental retardation. In turn, these results may also shed fight on mechanisms involved in cognitive functions. [ABSTRACT FROM AUTHOR]

Background/Aims: Nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver (NAFL) have a different prognosis and should be dealt with differently. The pathogenesis of NASH implicates the overexpression of cytochrome P450 2E1 (CYP2E1). We investigated whether the noninvasive determination of CYP2E1 activity could replace a liver biopsy in order to differentiate NASH from NAFL. Method: Forty patients referred for suspicion of NASH underwent liver biopsy. In these patients, CYP2E1 activity was determined noninvasively by the 6-hydroxychlorzoxazone/chlorzoxazone (CHZ) ratio (CHZ test). Expression of CYP2E1 on liver slides was assessed by immunohistochemistry, and immunostaining for smooth muscle actin was used to assess the activation of hepatic stellate cells (HSC). Results: Thirty patients with NASH were compared with 10 subjects with NAFL. No statistically significant difference could be identified for the clinical and biochemical parameters between the two groups. In the histology, steatosis was more important in NASH than in NAFL ( P<0.0001). There was no difference either in the activity (CHZ test) or in the expression of CYP2E1 (immunohistochemistry) between patients with NASH and patients with NAFL. The degree of HSC activation was also comparable between the two groups. A positive and significant correlation was found between the activity of CYP2E1 and body mass index ( P<0.001) as well as with the degree of steatosis ( P=0.008). Conclusion: For patients suspected to have NASH, noninvasive tests including the determination of the CYP2E1 activity are unable to distinguish them from patients with steatosis. [ABSTRACT FROM AUTHOR]

It is postulated that nitric oxide (NO) is responsible for the hyperdynamic circulation of portal hypertension. Therefore, we investigated induction of fibrosis and hyperdynamic circulation in endothelial NO synthase knock-out (KO) mice. Methods: Fibrosis was induced by bile duct ligation. Hemodynamic studies were performed after portal vein ligation. All studies were performed in wild-type (WT) and KO mice. Results: Three to 4 weeks after bile duct ligation (BDL), both WT and KO groups had similar degrees of portal hypertension, 12 (9–14) and 11(8–15) mmHg, median (range), and liver function. Fibrosis increased from 0.0% in sham operated to 1.0 and 1.1% in WT and KO mice, respectively. Cardiac output was similar after portal vein ligation (20 and 17 ml/min in WT and KO mice, respectively). There was no difference in liver of mRNA for endothelin 1, inducible NO synthase (iNOS) and hem-oxygenase 1 (HO1); proteins of iNOS, HO1 and HO2; nor in endothelin A and B (EtA and EtB) receptor density between WT and KO mice after BDL. Conclusions: These results suggest that endothelial NO synthase is neither essential for the development of fibrosis and portal hypertension in bile duct ligated mice, nor for the hyperdynamic circulation associated with portal hypertension in the portal vein ligated mice. [ABSTRACT FROM AUTHOR]

Abstract Objective To contribute further to the understanding of cognitive and psychosocial outcome of children with end-stage renal disease undergoing long-term peritoneal dialysis. Methods In total, 16 surviving infants at a single centre beginning peritoneal dialysis in the first year of life were studied. The age range of the children at assessment was 1.6–12.1 years. Children were assessed using the Griffiths Mental Development Scales, the Wechsler Intelligence Scale for Children – Third Edition UK, and the Strengths and Difficulties Questionnaire. Information regarding the child's hospital stay and family background was also collated. A Pearson's Product Moment correlation was used to analyse the results. Results Although 67% of the children's scores fell within the average range, 87% were within at least two SDs of the norms (mean IQ = 86.6). Psychosocial adjustment measures revealed that 50% of scores fell within the borderline to abnormal category, suggesting that the frequency of psychological difficulties was above that of the normal population. Conclusions These findings lend support to recent studies indicating that, developmentally, children undergoing long-term peritoneal dialysis are faring better than in the past. This may indeed be a reflection of improvements in renal treatment and diet. The behavioural results suggest the need to monitor psychological adjustment in this group of children. [ABSTRACT FROM AUTHOR]

The agent that causes prion diseases is thought to be identical with PrPSc, a conformer of the normal prion protein PrPC. PrPC-deficient mice do not exhibit major pathologies, perhaps because they express a protein termed Dpl, which shares significant biochemical and structural homology with PrPC. To investigate the physiological function of Dpl, we generated mice harbouring a homozygous disruption of the Prnd gene that encodes Dpl. Dpl deficiency did not interfere with embryonic and postnatal development, but resulted in mate sterility. Dpl protein was expressed at late stages of spermiogenesis, and spermatids of Dpl mutants were reduced in numbers, immobile, malformed and unable to fertilize oocytes in vitro. Mechanical dissection of the zona pellucida partially restored in vitro fertilization. We conclude that Dpl regulates male fertility by controlling several aspects of male gametogenesis and sperm-egg interaction. [ABSTRACT FROM AUTHOR]

Background: In previous studies, tropisetron has been shown to accelerate gastric emptying of a solid meal. However, it is uncertain whether other specific 5-hydroxytryptamine-3 receptor antagonists, such as ondansetron, also have a gastroprokinetic effect in humans. Aim: To evaluate the effect of ondansetron on gastric half-emptying time (T1/2) of a solid meal, gastric myoelectrical activity and hormone levels in 14 healthy volunteers. Methods: In a placebo-controlled, randomized, crossover study, we investigated the effects of ondansetron (8 mg intravenously) on the gastric emptying of solids (by scintigraphy), gastric myoelectrical activity (by electrogastrography) and the post-prandial release of cholecystokinin, gastrin, human pancreatic polypeptide, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, motilin, substance P and galanin. Results: The average T1/2 values were 86 min and 85.5 min without lag time (P=0.082) and 92 min and 93 min with lag time (P=0.158) for the placebo and ondansetron treatments, respectively. The average T1/2 of female volunteers was significantly longer than that of male volunteers. The dominant gastric electrical frequency and hormone plasma concentrations were not altered by ondansetron. Conclusions: Ondansetron did not affect the gastric emptying of solids, the dominant gastric electrical frequency or the plasma concentrations of the analysed gastrointestinal peptides. [ABSTRACT FROM AUTHOR]