PhenoWorld : a new paradigm to screen rodent behavior

Modeling depression in animals has inherent complexities that are augmented by intrinsic difficulties to measure the characteristic features of the disorder. Herein, we describe the PhenoWorld (PhW), a new setting in which groups of six rats lived in an ethological enriched environment, and have their feeding, locomotor activity, sleeping and social behavior automatically monitored. A battery of emotional and cognitive tests was used to characterize the behavioral phenotype of animals living in the PhW and in standard conditions (in groups of six and two rats), after exposure to an unpredictable chronic mild stress paradigm (uCMS) and antidepressants. Data reveal that animals living in the PhW displayed similar, but more striking, behavioral differences when exposed to uCMS, such as increased behavioral despair shown in the forced swimming test, resting/sleep behavior disturbances and reduced social interactions. Moreover, several PhW-cage behaviors, such as spontaneous will to go for food or exercise in running wheels, proved to be sensitive indicators of depressive-like behavior. In summary, this new ethological enriched paradigm adds significant discriminative power to screen depressive-like behavior, in particularly rodent's hedonic behavior

Atomistic characterization of the active-site solvation dynamics of a model photocatalyst

The interactions between the reactive excited state of molecular photocatalysts and surrounding solvent dictate reaction mechanisms and pathways, but are not readily accessible to conventional optical spectroscopic techniques. Here we report an investigation of the structural and solvation dynamics following excitation of a model photocatalytic molecular system [Ir-2(dimen)(4)](2+), where dimen is para-diisocyanomenthane. The time-dependent structural changes in this model photocatalyst, as well as the changes in the solvation shell structure, have been measured with ultrafast diffuse X-ray scattering and simulated with Born-Oppenheimer Molecular Dynamics. Both methods provide direct access to the solute-solvent pair distribution function, enabling the solvation dynamics around the catalytically active iridium sites to be robustly characterized. Our results provide evidence for the coordination of the iridium atoms by the acetonitrile solvent and demonstrate the viability of using diffuse X-ray scattering at free-electron laser sources for studying the dynamics of photocatalysis.1

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II

PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL

Analysis of decisions made in meta-analyses of depression screening and the risk of confirmation bias: a case study

Background: Depression is common in primary care and clinicians are encouraged to screen their patients. Metaanalyses have evaluated the effectiveness of screening, but two author groups consistently reached completely opposite conclusions. Methods: We identified five systematic reviews on depression screening conducted between 2001 and 2009, three by Gilbody and colleagues and two by the United States Preventive Task Force. The two author groups consistently reached completely opposite conclusions. We analyzed two contemporaneous systematic reviews, applying a stepwise approach to unravel their methods. Decision points were identified, and discrepancies between systematic reviews authors justification of choices made were recorded. Results: Two systematic reviews each addressing three research questions included 26 randomized controlled trials with different combinations in each review. For the outcome depression screening resulting in treatment, both reviews undertook meta-analyses of imperfectly overlapping studies. Two in particular, pooled each by only one of the reviews, influenced the recommendations in opposite directions. Justification for inclusion or exclusion of studies was obtuse. Conclusion: Systematic reviews may be less objective than assumed. Based on this analysis of two meta-analyses we hypothesise that strongly held prior beliefs (confirmation bias) may have influenced inclusion and exclusion criteria of studies, and their interpretation. Authors should be required to declare a priori any strongly held prior beliefs within their hypotheses, before embarking on systematic reviews

Analysis of decisions made in meta-analyses of depression screening and the risk of confirmation bias: a case study

Background: Depression is common in primary care and clinicians are encouraged to screen their patients. Metaanalyses have evaluated the effectiveness of screening, but two author groups consistently reached completely opposite conclusions. Methods: We identified five systematic reviews on depression screening conducted between 2001 and 2009, three by Gilbody and colleagues and two by the United States Preventive Task Force. The two author groups consistently reached completely opposite conclusions. We analyzed two contemporaneous systematic reviews, applying a stepwise approach to unravel their methods. Decision points were identified, and discrepancies between systematic reviews authors justification of choices made were recorded. Results: Two systematic reviews each addressing three research questions included 26 randomized controlled trials with different combinations in each review. For the outcome depression screening resulting in treatment, both reviews undertook meta-analyses of imperfectly overlapping studies. Two in particular, pooled each by only one of the reviews, influenced the recommendations in opposite directions. Justification for inclusion or exclusion of studies was obtuse. Conclusion: Systematic reviews may be less objective than assumed. Based on this analysis of two meta-analyses we hypothesise that strongly held prior beliefs (confirmation bias) may have influenced inclusion and exclusion criteria of studies, and their interpretation. Authors should be required to declare a priori any strongly held prior beliefs within their hypotheses, before embarking on systematic reviews