Investigation of amphibian mortality events in wildlife reveals an on-going ranavirus epidemic in the North of the Netherlands

In the four years following the first detection of ranavirus (genus Ranavirus, family Iridoviridae) infection in Dutch wildlife in 2010, amphibian mortality events were investigated nationwide to detect, characterize and map ranaviruses in amphibians over time, and to establish the affected host species and the clinico-pathological presentation of the disease in these hosts. The ultimate goal was to obtain more insight into ranavirus disease emergence and ecological risk. In total 155 dead amphibians from 52 sites were submitted between 2011 and 2014, and examined using histopathology, immunohistochemistry, virus isolation and molecular genetic characterization. Ranavirus-associated amphibian mortality events occurred at 18 sites (35%), initially only in proximity of the 2010 index site. Specimens belonging to approximately half of the native amphibian species were infected, including the threatened Pelobates fuscus (spadefoot toad). Clustered massive outbreaks involving dead adult specimens and ranavirus genomic identity indicated that one common midwife toad virus (CMTV)-like ranavirus strain is emerging in provinces in the north of the Netherlands. Modelling based on the spatiotemporal pattern of spread showed a high probability that this emerging virus will continue to be detected at new sites (the discrete reproductive power of this outbreak is 0.35). Phylogenetically distinct CMTV-like ranaviruses were found in the south of the Netherlands more recently. In addition to showing that CMTV-like ranaviruses threaten wild amphibian populations not only in Spain but also in the Netherlands, the current spread and risk of establishment reiterate that understanding the underlying causes of CMTV-like ranavirus emergence requires international attention

The dynamics of decision-making in weight loss and maintenance: a qualitative enquiry

This is the final version. Available on open access from BMC via the DOI in this recordBackground . Behavioural approaches to weight loss are often initially successful but less so in the longer term, as some people maintain the necessary behaviour changes while others do not. This study aimed to derive possible explanations for this using a qualitative approach with a view to improving intervention effectiveness. Methods . Thirty-six participants in a development and feasibility study for a weight loss and maintenance intervention (called SkiM) were interviewed three times over 18 months regarding their experiences before, during and after the intervention. Data were analysed thematically. The accounts of those who were more and less successful in terms of longer term weight loss were compared, and a conceptual model linking the main analytic themes was developed. Results. Five interpretative themes were generated: encountering and managing key situations; the impact of emotion; the source of control; personal values; and acquiring knowledge and skills. These themes were linked through a model of decision-making during key situations. In this model, behavioural decisions emerge from a dynamic interplay between several drivers: emotional state and needs, perceived control, personal values, the individual’s knowledge and skills, and their existing habits. The individual’s response in key situations generates experiential learning that caninfluence decisional dynamics in similar situations in future. These dynamics appeared to differ between participants, and between those who were more and less successful in weight management. Conclusions. Our analysis and model of decision-making during weight-management have implications for the development and delivery of behavioural weight management interventions. By helping individuals to identify the drivers of their decision-making in key situations, and equipping them to manage these drivers, programmes may enhance their capacity to sustain the behaviour changes needed for long-term weight loss.National Institute for Health Research (NIHR

Towards user-adapted training paradigms: physiological responses to physical threat during cognitive task performance

Feedback of physiological responses have a great potential to support virtual training paradigms aimed to increase cognitive task performance under stressful threatening conditions. In the current study, we examined the sensitivity of a range of physiological indicators derived from electrodermal activity (EDA), blood pressure (BP) and heart rate (HR) to measure stress as induced by the threat of an electric shock (ES). In contrast to previous work that studied physiological stress responses compared to a rest condition, we compared conditions with high cognitive load combined with stress caused by threat of an ES, to conditions with high cognitive load without such stress. Twenty-five participants performed a cognitively demanding task in an experimental setup. At certain 10 s time intervals, indicated by a continuous tone, participants were either asked to do their best and increase cognitive task performance (non-threat condition), or they were told that they could receive an ES during this interval if cognitive task performance was not high enough (threat condition). Physiological measures, task performance and self-reported measures of stress and workload were analysed. Task performance and self-reported measures of stress and workload were roughly the same in both conditions. Especially EDA measures were affected by the threat of an ES. Threat and non-threat conditions could be distinguished with an across-participant classifier using EDA and BP features with an accuracy of 70%. These results suggest that EDA and BP can be used to evaluate stress coping training paradigms or to individually adapt the stress levels in virtual training environments.Stress-related psychiatric disorders across the life spa

The Paget Trial:topical 5% imiquimod cream for noninvasive vulvar Paget disease

BACKGROUND: Vulvar Paget disease is an extremely rare skin disorder, which is most common in postmenopausal women. Most vulvar Paget disease cases are noninvasive; however, it may be invasive or associated with an underlying vulvar or distant adenocarcinoma. The current treatment of choice for noninvasive vulvar Paget disease is wide local excision, which is challenging because of extensive intraepithelial spread and may cause severe morbidity. Recurrence rates are high, ranging from 15% to 70%, which emphasizes the need for new treatment options. Imiquimod, a topical immune response modifier, has been shown to be effective in a few studies and case reports, and is a promising new treatment modality. OBJECTIVE: To prospectively investigate the efficacy, safety, and effect on quality of life of a standardized treatment schedule with 5% imiquimod cream in patients with noninvasive vulvar Paget disease. STUDY DESIGN: The Paget Trial is a multicenter prospective observational clinical study including 7 tertiary referral hospitals in the Netherlands. A total of 24 patients with noninvasive vulvar Paget disease were treated with topical 5% imiquimod cream 3 times a week for 16 weeks. The primary efficacy outcome was the reduction in lesion size at 12 weeks after the end of treatment. Secondary outcomes were safety, clinical response after 1 year, and quality of life. Safety was assessed by evaluation of adverse events and tolerability of treatment. Quality of life was investigated with 3 questionnaires taken before, during, and after treatment. RESULTS: Data were available for 23 patients, 82.6% of whom responded to therapy. A complete response was reported in 12 patients (52.2%), and 7 patients (30.4%) had a partial response. A histologic complete response was observed in 10 of the 12 patients with a complete response. Patients experienced side effects such as fatigue (66.7%-70.9%) and headaches (16.7%-45.8%), and almost 80% needed painkillers during treatment. Eight patients (34.8%) adjusted the treatment protocol to 2 applications a week, and 3 patients (13.0%) stopped treatment because of side effects after 4 to 11 weeks. Treatment improved quality of life, whereas a slight, temporary negative impact was observed during treatment. Two patients with a complete response developed a recurrence within 1 year after treatment. Follow-up showed 6 patients with a noninvasive recurrence after a median of 31 months (14-46 months) after the end of treatment. CONCLUSION: Topical 5% imiquimod cream can be an effective and safe treatment alternative for noninvasive vulvar Paget disease, particularly when compared with treatment with surgical excision

Occupational physicians' perceived barriers and suggested solutions to improve adherence to a guideline on mental health problems: Analysis of a peer group training

Background: Despite the impact of mental health problems on sickness absence, only few occupational health guidelines addressing these problems are available. Moreover, adherence has found to be suboptimal. To improve adherence to the Dutch guideline on mental health problems a training was developed for Dutch occupational physicians (OPs) focusing on identifying barriers and addressing them. The aim of this study was to provide an overview of the barriers that OPs perceived in adhering to the Dutch guideline on mental health problems as well as their solutions to overcome them. Methods: A qualitative study was conducted using data from the peer group training. Thirty-two (6 groups of 4 to 6) OPs received a multiple-session interactive training over the course of a year, focusing on identifying and addressing barriers, using a Plan-Do-Check-Act approach. Sessions were audio-taped and transcribed verbatim. Thematic content analysis was performed by two researchers with a selection of 50 % (21 out of 42) of the transcripts to identify the perceived barriers and the suggested solutions, using AtlasTi 7.0. Results: Knowledge-related barriers were perceived regarding the content of all parts of the guideline. Commonly perceived attitude-related barriers were a lack of self-efficacy to perform certain guideline recommendations and difficulties with changing habits and routines. External barriers that were commonly perceived were work-contextual barriers, such as a lack of time/work pressure, tight contracts between occupational health services (OHSs) and employers, and conflicting policy of and a lack of collaboration with other parties (e.g. employer, other healthcare providers). The most often tested solutions by OPs during the training were sharing information, experiences, tips and tricks and referring to existing tools, or developing new tools to facilitate guideline usage. Conclusions: Dutch OPs perceive a range of knowledge-related, attitude-related and external barriers in adhering to the guideline on mental health problems. The tested solutions during the training particularly seemed to focus on knowledge and attitude-related barriers. To optimally implement this or similar mental health guidelines, it may be important to complement guideline training and education of individual or groups of OPs, with interventions that address external barriers such as changing

Domain integral equations for electromagnetic band-gap slab simulations

Trabajo presentado al International Symposium on Electromagnetic Theory, URSI 2004.Electromagnetic band-gap substrates o er advantages regarding cross-coupling in sub-mm range imaging array applications. Electromagnetic scattering by such substrates may e ectively be formulated in terms of integro- di erential equations. The scattered elds are evaluated via the spectral domain in which the 3-D problem reduces to an in nite system of coupled 1-D integro-di erential equations. The associated matrix-vector products are dominated by FFTs. For moderate frequencies an elementary preconditioner in combination with a prudent initial estimate usually su ces to reach rapid convergence using the transpose-free quasi-minimal residual method.The research presented above has been financially supported by ESA/ESTEC, under Contract No. 15632/01/NL/JA

Role of Local and/or Metastasis-directed Therapy in Patients with Hormone-sensitive M1a Prostate Cancer:A Systematic Review

CONTEXT: It remains unclear whether men with hormone-sensitive prostate cancer (PCa) metastasized to nonregional lymph nodes (M1a) benefit from prostate-directed therapy (PDT) and/or metastasis-directed therapy (MDT). OBJECTIVE: To systematically summarize the literature regarding oncological outcomes of de novo and recurrent M1a PCa patients treated with PDT and/or MDT. EVIDENCE ACQUISITION: We searched Medline (Ovid), Embase, and Scopus according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for reports on oncological outcomes of de novo or recurrent hormone-sensitive M1a PCa patients treated with PDT (radical prostatectomy or radiotherapy) and/or MDT (nodal radiotherapy or salvage lymph node dissection) with or without androgen deprivation therapy. A descriptive data synthesis and a methodological quality assessment were performed to evaluate the impact of PDT and/or MDT on survival in M1a PCa patients. EVIDENCE SYNTHESIS: A total of 6136 articles were screened and 24 studies were included in this systematic review. In de novo M1a PCa patients, PDT was associated with improved oncological outcomes compared with no PDT. In recurrent M1a PCa, MDT could delay the need for systemic treatment in a selection of patients, but high-level evidence from prospective phase III randomized controlled trials is still awaited. CONCLUSIONS: This systematic review summarized the limited literature data on the management of M1a PCa. Subgroup analyses suggest a role for PDT plus systemic therapy in de novo M1a PCa. MDT to distant nodal metastases delayed the need for systemic therapy in recurrent disease, but robust data are lacking. The predominantly retrospective nature of the included studies and significant heterogeneity in study designs limit the strength of evidence. PATIENT SUMMARY: We reviewed the treatment of patients with prostate cancer that has spread to lymph nodes outside the pelvis without metastases in other organ systems. There is evidence that treatment of the primary prostate tumor improves outcomes in well-selected patients and that treatment targeting distant lymph node metastases can delay the start of systemic treatment.</p

Selective Reporting of Outcomes in Tinnitus Trials: Comparison of Trial Registries With Corresponding Publications

Objectives: We aimed to study the prevalence of selective reporting of primary and secondary outcomes in tinnitus trials and to examine if selective reporting of outcome measures is influenced by the nature and direction of its results. Background: Selective reporting of outcome measures has been reported in several biomedical fields and can influence the clinical usefulness and implementation of outcomes of clinical trials. It is reported as one of the obstacles in finding an effective intervention for tinnitus. Methods: ClinicalTrials.gov (CT.gov) was used to identify all registered interventional tinnitus trials up to December 2015. A standardized search was used to find corresponding publications up to March 2018. The prespecified outcomes in CT.gov were compared with the outcomes reported in corresponding publication(s). The effects of the (lack of) statistical significance of trial results and the effects of funding source on record adherence were evaluated. Changes in registration elements were assessed with the Archive site of CT.gov. Results: We found corresponding publications for 60 (64.5%) of 93 eligible tinnitus trials registered in CT.gov. Of all the publications, five (7.5%) fully reported outcome measures entirely in line with the prespecified outcome measures. Discrepancies between the prespecified and reported outcomes were found in a total of 51 (76.1%) of the studies for primary outcomes, whereas 62 (92.5%) of the studies had discrepancies in secondary outcomes. In secondary outcomes, statistical significance of trial results influenced CT.gov record adherence. In addition, there was a statistically significant difference in the rate of discrepancy in industry-funded [n = 98 (87.5%) discrepant outcomes] and non-industry funded trials [n = 172 (74.5%) discrepant outcomes] (p = 0.01). Finally, 15 (25.9%) trialists made modifications in registered outcome measures during or after the trial period. Conclusion: Tinnitus trials suffer from substantial outcome reporting bias. Awareness of its presence must be raised to limit the obstacles of finding an effective intervention for tinnitus

CO-induced lifting of Au (001) surface reconstruction

We report CO-induced lifting of the hexagonal surface reconstruction on Au (001). Using in-situ surface x-ray scattering, we determined a pressure-temperature phase diagram for the reconstruction and measured the dynamical evolution of the surface structure in real time. Our observations provide evidence that, under certain conditions, even macroscopic Au surfaces, much larger than catalytic Au nanoparticles [M. Haruta, Catal. Today 36, 153 (1997)], can exhibit some of the reactive properties and surface transitions observed in systems known to be catalytically active such as Pt (001).Comment: 4 Figures. Accepted as a Letter to Journal of Physical Chemistry

Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers

Background:It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis.Methods:We included 386 BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC.Results:BRCA-associated EOC patients with, vs without, a BC history had a significantly worse PFS and PFI (multivariate hazard ratio (HR mult) 1.47; 95% confidence interval (CI) 1.03-2.08 and HR mult 1.43; 95% CI 1.01-2.03), and a non-significantly worse OS (HR mult 1.15; 95% CI 0.84-1.57) and OCSS (HR mult 1.18; 95% CI 0.85-1.62). Ovarian cancer-specific survival was significantly worse for the subgroup treated with adjuvant chemotherapy for BC (HR mult 1.99; 95% CI 1.21-3.31).Conclusions:Our results suggest that BRCA1/2-associated EOC patients with a previous BC have a worse outcome than EOC patients without BC, especially when treated with adjuvant chemotherapy