The Effects of Intranasal Oxytocin Administration on Sensitive Caregiving in Mothers with Postnatal Depression

Development Psychopathology in context: famil

GNAQ and GNA11 mutations and downstream YAP activation in choroidal nevi

Dermatology-oncolog

GNAQ and GNA11 mutations and downstream YAP activation in choroidal nevi

Background: Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations.Methods: We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant nevus cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation.Results: For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the nevus cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi.Conclusions: Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal nevus cells. We hypothesise that GNAQ/11 mutant-driven extracellular mitogenic signalling involving YAP activation leads to accumulation of wild-type nevus cells

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Role of editorial and peer review processes in publication bias: analysis of drug trials submitted to eight medical journals

Contains fulltext : 136751.pdf (publisher's version ) (Open Access)BACKGROUND: Publication bias is generally ascribed to authors and sponsors failing to submit studies with negative results, but may also occur after submission. We evaluated whether submitted manuscripts on randomized controlled trials (RCTs) with drugs are more likely to be accepted if they report positive results. METHODS: Manuscripts submitted from January 2010 through April 2012 to one general medical journal (BMJ) and seven specialty journals (Annals of the Rheumatic Diseases, British Journal of Ophthalmology, Gut, Heart, Thorax, Diabetologia, and Journal of Hepatology) were included, if at least one study arm assessed the efficacy or safety of a drug and a statistical test was used to evaluate treatment effects. Publication status was retrospectively retrieved from submission systems or provided by journals. Sponsorship and trial results were extracted from manuscripts and classified according to predefined criteria. Main outcome measure was acceptance for publication. RESULTS: Of 15,972 manuscripts submitted, 472 (3.0%) were drug RCTs, of which 98 (20.8%) were published. Among submitted drug RCTs, 287 (60.8%) had positive and 185 (39.2%) negative results. Of these, 60 (20.9%) and 38 (20.5%), respectively, were published. Manuscripts on non-industry trials (n = 213) reported positive results in 138 (64.8%) manuscripts, compared to 71 (47.7%) on industry-supported trials (n = 149), and 78 (70.9%) on industry-sponsored trials (n = 110). Twenty-seven (12.7%) non-industry trials were published, compared to 27 (18.1%) industry-supported and 44 (40.0%) industry-sponsored trials. After adjustment for other trial characteristics, manuscripts reporting positive results were not more likely to be published (OR, 1.00; 95% CI, 0.61 to 1.66). Submission to specialty journals, sample size, multicentre status, journal impact factor, and corresponding authors from Europe or US were significantly associated with publication. CONCLUSIONS: For the selected journals, there was no tendency to preferably publish manuscripts on drug RCTs that reported positive results, suggesting that publication bias may occur mainly prior to submission

Shortcomings of protocols of drug trials in relation to sponsorship as identified by Research Ethics Committees: analysis of comments raised during ethical review

Contains fulltext : 138715.pdf (publisher's version ) (Open Access)BACKGROUND: Submission of study protocols to research ethics committees (RECs) constitutes one of the earliest stages at which planned trials are documented in detail. Previous studies have investigated the amendments requested from researchers by RECs, but the type of issues raised during REC review have not been compared by sponsor type. The objective of this study was to identify recurring shortcomings in protocols of drug trials based on REC comments and to assess whether these were more common among industry-sponsored or non-industry trials. METHODS: Retrospective analysis of 226 protocols of drug trials approved in 2010-2011 by three RECs affiliated to academic medical centres in The Netherlands. For each protocol, information on sponsorship, number of participating centres, participating countries, study phase, registration status of the study drug, and type and number of subjects was retrieved. REC comments were extracted from decision letters sent to investigators after review and were classified using a predefined checklist that was based on legislation and guidelines on clinical drug research and previous literature. RESULTS: Most protocols received comments regarding participant information and consent forms (n = 182, 80.5%), methodology and statistical analyses (n = 160, 70.8%), and supporting documentation, including trial agreements and certificates of insurance (n = 154, 68.1%). Of the submitted protocols, 122 (54.0%) were non-industry and 104 (46.0%) were industry-sponsored trials. Non-industry trials more often received comments on subject selection (n = 44, 36.1%) than industry-sponsored trials (n = 18, 17.3%; RR, 1.58; 95% CI, 1.01 to 2.47), and on methodology and statistical analyses (n = 95, 77.9% versus n = 65, 62.5%, respectively; RR, 1.18; 95% CI, 1.01 to 1.37). Non-industry trials less often received comments on supporting documentation (n = 72, 59.0%) than industry-sponsored trials (n = 82, 78.8%; RR, 0.83; 95% CI, 0.72 to 0.95). CONCLUSIONS: RECs identified important ethical and methodological shortcomings in protocols of both industry-sponsored and non-industry drug trials. Investigators, especially of non-industry trials, should better prepare their research protocols in order to facilitate the ethical review process

Tackling conflicts of interest. Industry tie may be benchmark of quality.

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Hamsters (cricetus cricetus) and camera - use of a camera for collecting biological data about number of litters and the gain of weight of young in the first two months.

Contains fulltext : 91876.pdf (publisher's version ) (Open Access)4 p

Parental PTSD, adverse parenting and child attachment in a refugee sample

Item does not contain fulltextIn contrast with traumatic experiences, there is a dearth of studies on the link between trauma symptoms, disconnected (frightened, threatening and dissociative) parenting behavior, extremely insensitive parenting behavior and child attachment. This study extends previous work on the impact of posttraumatic stress disorder (PTSD) on families by studying the unique contribution of disconnected and extremely insensitive parenting behavior on child attachment in a highly traumatized sample of 68 asylum seekers and refugees and their children (18-42 months). The results show that parental symptoms of PTSD are directly related to children's insecure attachment and disorganized attachment. The greatest proportion of the risk could be attributed to factors related to the dyad and not the family. A mediation effect of adverse parenting behavior was not confirmed. On the one hand the results indicate the need for an effective treatment of PTSD symptomatology while on the other hand the results indicate the need for clinical attention to insecure attachment relationships.19 p

State and trait variance in salivary α-amylase: a behavioral genetic study

This is the first behavior genetic study of salivary α-amylase (sAA), focusing on genetic and environmental influences on stability and change in sAA during baseline and exposure to infant crying. The sample consisted of 184 adult twin pairs. Although there was significant variation between individuals in basal levels of sAA and in responsivity to infant crying, strong stability in sAA concentrations across conditions was found. Similar genetic mechanisms influenced sAA at baseline and in response to cry sounds (explained variance: 51-62%), accounting for part of the stability in sAA. Unique environmental factors explained the remaining variance in sAA, some of them only emerging in response to the cry sounds, explaining individual differences in the pattern of reactivity. These findings confirm that sAA is sensitive to the effects of potentially stressful stimuli (state variance) and at the same time demonstrate its relative robustness and stability across time and conditions (trait variance).Afdeling Klinische Chemie en Laboratoriumgeneeskunde (AKCL