The impact of inter-cycle treatment delays on overall survival in patients with advanced-stage ovarian cancer

INTRODUCTION: Chemotherapy forms the cornerstone of systemic treatment for advanced ovarian cancer, extending overall survival; however, drug-related toxicity can lead to treatment delays, potentially diminishing treatment efficacy. This study evaluated the impact of treatment delays on all-cause mortality of patients with ovarian cancer, to better inform decisions on patient management. METHODS: This retrospective, population-based cohort study included 1517 women with advanced-stage ovarian cancer, receiving first-line adjuvant or neoadjuvant chemotherapy in 2014 and 2015. The frequency of inter-cycle delays >7 days was calculated using drug administration dates. Kaplan-Meier estimates were used to compare 2-year overall survival (OS) between patients who were delayed and those treated to schedule. Cox proportional hazards regression was used to investigate the impact of treatment delay on all-cause mortality. Inverse probability of treatment weighting propensity scores were used to adjust for confounding variables. RESULTS: Delays >7 days occurred in 35.3% of patients. Two-year OS probability was 62.7% in patients who experienced treatment delays >7 days (95% CI, 58.7-66.9) compared to 69.1% in those treated to schedule (95% CI, 66.2-72.0). Delays were not significantly associated with all-cause mortality when adjusted for confounders (HR 1.00 95% CI, 0.83-1.20, P = .9). CONCLUSIONS: Delays to chemotherapy treatment were not significantly associated with worsened survival in patients with advanced-stage ovarian cancer. These results can inform clinical decision making that prioritize toxicity management and quality of life for those treated with chemotherapy

Developing standards for reporting implementation studies of complex interventions (StaRI): a systematic review and e-Delphi

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Crosstalk between the EGFR and other signalling pathways at the level of the global transcriptional corepressor Groucho/TLE

In this minireview, we briefly revisit the Drosophila Notch and epidermal growth factor receptor pathways, and relate to the relationship between them. We then mainly focus on the involvement of Groucho (Gro)/TLE, a global developmental corepressor, in these pathways. In particular, we discuss Gro/TLE's role at the junction between these two signal transduction cascades

Variation in the intermittent buzzing songs of male medflies (diptera: tephritidae) associated with geography, mass-rearing, and courtship success

Varios aspectos de los patrones temporales de los sonidos del zumbido intermitente producido durante el cortejo pre-copulatório de los machos de la mosca del Mediterráneo variaron entre moscas silvestres de Costa Rica, Argentina y Hawaii, y entre moscas de sepas de cría masiva de Costa Rica, Argentina, Mexico y Hawaii. No se presentaron diferencias consistentes cuando se compararon las sepas de cría masiva en Costa Rica, Argentina y Hawaii con moscas silvestres de los sitios de origen. Los sonidos producidos durante cortejos que terminaron en cópulas no difieron de los sonidos producidos durante cortejos que llevaron a montas que fracasaron en moscas de Costa Rica y Argentina. Pero en sepas de todos los sitios los zumbidos intermitentes que incluyeron pequeñas pausas tuvieron una mayor probabilidad de no terminar en un intento de monta. Los zumbidos intermitentes de las moscas de las crias masivas tuvieron una tendencia leve a interumpirse mas frecuentemente.Many aspects of the temporal pattern of sounds produced during the intermittent buzzing displays of pre-copulatory courtship by male medflies varied between wild flies from Costa Rica, Argentina, and Hawaii, and between mass-reared flies from Costa Rica, Argentina, Mexico, and Hawaii. There were no consistent differences when mass-reared strains were compared with the wild strains from the area where they originated in Costa Rica, Argentina and Hawaii. Buzzing sounds produced prior to successful mounting attempts did not differ consistently from those preceding unsuccessful mounts in flies from Costa Rica and Argentina. In strains from all sites, however, courtships in which buzzes were interrupted were more likely not to result in mounting of the female. There was a weak tendency for interruptions to be more common in mass-reared strains.Universidad de Costa Rica. Universidad de Buenos Aires. El Colegio de la Frontera Sur, Tapachula, Chiapas, Mexico. USDA-ARS.UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biologí

Quality of intervention delivery in a cluster randomised controlled trial : a qualitative observational study with lessons for implementation fidelity

Abstract Background Understanding intervention fidelity is an essential part of the evaluation of complex interventions because fidelity not only affects the validity of trial findings, but also because studies of fidelity can be used to identify barriers and facilitators to successful implementation, and so provide important information about factors likely to impact the uptake of the intervention into clinical practice. Participant observation methods have been identified as being particularly valuable in studies of fidelity, yet are rarely used. This study aimed to use these methods to explore the quality of implementation of a complex intervention (Safewards) on mental health wards during a cluster randomised controlled trial. Specific aims were firstly to describe the different ways in which the intervention was implemented, and secondly to explore the contextual factors moderating the quality of intervention delivery, in order to inform ‘real world’ implementation of the intervention. Methods Safewards was implemented on 16 mental health wards in England. We used Research Assistants (RAs) trained in participant observation to record qualitative observational data on the quality of intervention delivery (n = 565 observations). At the end of the trial, two focus groups were conducted with RAs, which were used to develop the coding framework. Data were analysed using thematic analysis. Results There was substantial variation in intervention delivery between wards. We observed modifications to the intervention which were both fidelity consistent and inconsistent, and could enhance or dilute the intervention effects. We used these data to develop a typology which describes the different ways in which the intervention was delivered. This typology could be used as a tool to collect qualitative observational data about fidelity during trials. Moderators of Safewards implementation included systemic, interpersonal, and individual factors and patient responses to the intervention. Conclusions Our study demonstrates how, with appropriate training in participant observation, RAs can collect high-quality observational data about the quality of intervention delivery during a trial, giving a more complete picture of ‘fidelity’ than measurements of adherence alone. Trial registration ISRCTN registry; IRSCTN38001825 . Registered 29 August 201

Shared computational principles for language processing in humans and deep language models

Departing from traditional linguistic models, advances in deep learning have resulted in a new type of predictive (autoregressive) deep language models (DLMs). Using a self-supervised next-word prediction task, these models generate appropriate linguistic responses in a given context. In the current study, nine participants listened to a 30-min podcast while their brain responses were recorded using electrocorticography (ECoG). We provide empirical evidence that the human brain and autoregressive DLMs share three fundamental computational principles as they process the same natural narrative: (1) both are engaged in continuous next-word prediction before word onset; (2) both match their pre-onset predictions to the incoming word to calculate post-onset surprise; (3) both rely on contextual embeddings to represent words in natural contexts. Together, our findings suggest that autoregressive DLMs provide a new and biologically feasible computational framework for studying the neural basis of language

Stimulus-Related Independent Component and Voxel-Wise Analysis of Human Brain Activity during Free Viewing of a Feature Film

Understanding how the brain processes stimuli in a rich natural environment is a fundamental goal of neuroscience. Here, we showed a feature film to 10 healthy volunteers during functional magnetic resonance imaging (fMRI) of hemodynamic brain activity. We then annotated auditory and visual features of the motion picture to inform analysis of the hemodynamic data. The annotations were fitted to both voxel-wise data and brain network time courses extracted by independent component analysis (ICA). Auditory annotations correlated with two independent components (IC) disclosing two functional networks, one responding to variety of auditory stimulation and another responding preferentially to speech but parts of the network also responding to non-verbal communication. Visual feature annotations correlated with four ICs delineating visual areas according to their sensitivity to different visual stimulus features. In comparison, a separate voxel-wise general linear model based analysis disclosed brain areas preferentially responding to sound energy, speech, music, visual contrast edges, body motion and hand motion which largely overlapped the results revealed by ICA. Differences between the results of IC- and voxel-based analyses demonstrate that thorough analysis of voxel time courses is important for understanding the activity of specific sub-areas of the functional networks, while ICA is a valuable tool for revealing novel information about functional connectivity which need not be explained by the predefined model. Our results encourage the use of naturalistic stimuli and tasks in cognitive neuroimaging to study how the brain processes stimuli in rich natural environments

Developing a decision aid to guide public sector health policy decisions: A study protocol

<p>Abstract</p> <p>Background</p> <p>Decision aids have been developed in a number of health disciplines to support evidence-informed decision making, including patient decision aids and clinical practice guidelines. However, policy contexts differ from clinical contexts in terms of complexity and uncertainty, requiring different approaches for identifying, interpreting, and applying many different types of evidence to support decisions. With few studies in the literature offering decision guidance specifically to health policymakers, the present study aims to facilitate the structured and systematic incorporation of research evidence and, where there is currently very little guidance, values and other non-research-based evidence, into the policy making process. The resulting decision aid is intended to help public sector health policy decision makers who are tasked with making evidence-informed decisions on behalf of populations. The intent is not to develop a decision aid that will yield uniform recommendations across jurisdictions, but rather to facilitate more transparent policy decisions that reflect a balanced consideration of all relevant factors.</p> <p>Methods/design</p> <p>The study comprises three phases: a modified meta-narrative review, the use of focus groups, and the application of a Delphi method. The modified meta-narrative review will inform the initial development of the decision aid by identifying as many policy decision factors as possible and other features of methodological guidance deemed to be desirable in the literatures of all relevant disciplines. The first of two focus groups will then seek to marry these findings with focus group members' own experience and expertise in public sector population-based health policy making and screening decisions. The second focus group will examine issues surrounding the application of the decision aid and act as a sounding board for initial feedback and refinement of the draft decision aid. Finally, the Delphi method will be used to further inform and refine the decision aid with a larger audience of potential end-users.</p> <p>Discussion</p> <p>The product of this research will be a working version of a decision aid to support policy makers in population-based health policy decisions. The decision aid will address the need for more structured and systematic ways of incorporating various evidentiary sources where applicable.</p

Bone Marrow Transplantation for Feline Mucopolysaccharidosis I

Severe mucopolysaccharidosis type I (MPS I) is a fatal neuropathic lysosomal storage disorder with significant skeletal involvement. Treatment involves bone marrow transplantation (BMT), and although effective, is suboptimal, due to treatment sequelae and residual disease. Improved approaches will need to be tested in animal models and compared to BMT. Herein we report on bone marrow transplantation to treat feline mucopolysaccharidosis I (MPS I). Five MPS I stably engrafted kittens, transplanted with unfractionated bone marrow (6.3 × 107–1.1 × 109 nucleated bone marrow cells per kilogram) were monitored for 13–37 months post-engraftment. The tissue total glycosaminoglycan (GAG) content was reduced to normal levels in liver, spleen, kidney, heart muscle, lung, and thyroid. Aorta GAG content was between normal and affected levels. Treated cats had a significant decrease in the brain GAG levels relative to untreated MPS I cats and a paradoxical decrease relative to normal cats. The α-l-iduronidase (IDUA) activity in the livers and spleens of transplanted MPS I cats approached heterozygote levels. In kidney cortex, aorta, heart muscle, and cerebrum, there were decreases in GAG without significant increases in detectable IDUA activity. Treated animals had improved mobility and decreased radiographic signs of disease. However, significant pathology remained, especially in the cervical spine. Corneal clouding appeared improved in some animals. Immunohistochemical and biochemical analysis documented decreased central nervous system ganglioside storage. This large animal MPS I study will serve as a benchmark of future therapies designed to improve on BMT

Neutralisation of Local Haemorrhage Induced by the Saw-Scaled Viper Echis carinatus sochureki

The objective of the study is to investigate the anti-snake venom activities of a local plant, Hibiscus aethiopicus L. The H. aethiopicus was dried and extracted with ethanol. Different assays were performed according to standard techniques, to evaluate the plant’s acute toxicity and its antivenom activities. The results of evaluating the systemic acute toxicity of the H. aethiopicus extract using “oral and intra-peritoneal” route were normal even at the highest dose (24 g/kg) tested. All guinea pigs (n=3) when treated with venoms E. c. sochureki (75 μg) alone induced acute skin haemorrhage. In contrast, all guinea pigs (n=18) treated with both venom and the plant extract at a concentration between 500 and 1000 mg/kg showed no signs of haemorrhage. Moreover, all guinea pigs (n=18) treated with venom and the plant extract below 400 mg/kg showed acute skin haemorrhage. All guinea pigs treated with venom E. c. sochureki (75 μg) alone induced acute skin haemorrhage after both 24 and 32 hours. In contrast, all guinea pigs treated with both venom and the plant extract (administered independently) at concentrations between 500 and 1000 mg/kg showed no signs of haemorrhage after 32 hours. However, after 24 hours all tested guinea pigs showed less inhibition (<60%) compared to that obtained after 32 hours. The outcome of this study reflects that the extract of H. aethiopicus plant may contain an endogenous inhibitor of venom induced local haemorrhage