Vinflunine in the treatment of relapsed metastatic urothelial cancer: A systematic review and meta-analysis of real-world series

Background. Vinflunine (VFL) is approved in Europe as second-line treatment of metastatic urothelial cancer after failure of platinum-containing therapy. We performed a systematic review and meta-analysis of real-world data (RWD) to assess utilization, efficacy and safety of VFL. Methods. We performed a MEDLINE search for the period of 1/1/2000-31/8/2017. Full-length articles providing post-marketing RWD on VFL in patients failing previous chemotherapy were eligible. Interventional clinical trials were excluded. Results: Ten studies with 797 patients were identified. According to pooled REs analysis, overall response rate was 19%, most frequent, all-grade toxicities were fatigue (41%), constipation (39%), nausea/vomiting (25%), and most prevalent Grade 3–4 toxicities were neutropenia (13%), anaemia (9%), fatigue (8%). Median OS was comparable to results reported in recent randomized studies. Conclusion. Our findings confirm the efficacy and safety of VFL in an unselected population and support the use of VFL in the changing treatment paradigm of relapsed mUC

Radiation-induced morphea of the breast: a case report

Radiation-induced morphea (RIM) of the breast is a rare complication of radiotherapy. It is disfiguring, painful and defeats the purpose of achieving a good cosmesis in breast-conservation surgery. This report describes a severe case of RIM in a breast cancer patient together with photographic illustrations of the serial changes over time and histopathology slides. A review of the literature is provided

The node of Ranvier in CNS pathology.

Healthy nodes of Ranvier are crucial for action potential propagation along myelinated axons, both in the central and in the peripheral nervous system. Surprisingly, the node of Ranvier has often been neglected when describing CNS disorders, with most pathologies classified simply as being due to neuronal defects in the grey matter or due to oligodendrocyte damage in the white matter. However, recent studies have highlighted changes that occur in pathological conditions at the node of Ranvier, and at the associated paranodal and juxtaparanodal regions where neurons and myelinating glial cells interact. Lengthening of the node of Ranvier, failure of the electrically resistive seal between the myelin and the axon at the paranode, and retraction of myelin to expose voltage-gated K(+) channels in the juxtaparanode, may contribute to altering the function of myelinated axons in a wide range of diseases, including stroke, spinal cord injury and multiple sclerosis. Here, we review the principles by which the node of Ranvier operates and its molecular structure, and thus explain how defects at the node and paranode contribute to neurological disorders

Neural Control of Rhythmic Sequences

We investigated whether the temporal structure of movement sequences can be represented and learned independently of their ordinal structure, and whether some brain regions are particularly important for temporal sequence performance. Using a learning transfer design, we found evidence for independent temporal representations: learning a spatiotemporal sequence facilitated learning its temporal and ordinal structure alone; learning a temporal and an ordinal structure facilitated learning of a sequence where the two were coupled. Second, learning of temporal structures was found during reproduction of sequential stimuli with random ordinal structure, suggesting independent mechanisms for temporal learning. We then used functional magnetic resonance imaging to investigate the neural control of sequences during well-learned performance. The temporal and ordinal structures of the sequences were varied in a 2 x 2 factorial design. A dissociation was found between brain regions involved in ordinal and temporal control, the latter mainly involving the presupplementary motor area, the inferior frontal gyrus and precentral sulcus, and the superior temporal gyri. Finally, in a second fMRI experiment, well-learned temporal sequences were performed with the left or right index fingers, or using rhythmic speech. The overlap in brain activity during performance with the different effectors included a similar set of brain regions as that found in the first fMRI experiment: the supplementary motor area (SMA), the superior temporal gyrus, and the inferior frontal cortex. We thus suggest that this set of regions is important for abstract, movement-independent, temporal sequence control. This organization may be important for increased flexibility in voluntarily timed motor tasks

Genetic influences on musical specialization: a twin study on choice of instrument and music genre

Though several studies show that genetic factors influence individual differences in musical engagement, aptitude, and achievement, no study to date has investigated whether specialization among musically active individuals in terms of choice of instrument and genre is heritable. Using a large twin cohort, we explored whether individual differences in instrument choice, instrument category, and the type of music individuals engage in can entirely be explained by the environment or are partly due to genetic influences. About 10,000 Swedish twins answered an extensive questionnaire about music-related traits, including information on the instrument and genre they played. Of those, 1259 same-sex twin pairs reported to either play an instrument or sing. We calculated the odds ratios (ORs) for concordance in music choices (if both twins played) comparing identical and nonidentical twin pairs, with significant ORs indicating that identical twins are more likely to engage in the same type of music-related behavior than are nonidentical twins. The results showed that for almost all music-related variables, the odds were significantly higher for identical twins to play the same musical instrument or music genre, suggesting significant genetic influences on such music specialization. Possible interpretations and implications of the findings are discussed

Why Is an Early Start of Training Related to Musical Skills in Adulthood? A Genetically Informative Study

Experts in domains such as music or sports often start training early. It has been suggested that this may reflect a sensitive period in childhood for skill acquisition. However, it could be that familial factors (e.g., genetics) contribute to the association. Here, we examined the effect of age of onset of musical training on musical aptitude and achievement in professional musicians (n = 310) and twins (n = 7,786). In line with previous literature, results showed that an earlier age of onset was associated with higher aptitude and achievement in both samples. After we adjusted for lifetime practice hours, age of onset was associated only with aptitude (p .14). Twin analyses showed that the association with aptitude was fully explained by familial factors. Thus, these findings provide little support for a sensitive period for music but highlight that familiar factors play an important role for associations between age of onset of training and skills in adulthood

The effects of playing music on mental health outcomes

The association between active musical engagement (as leisure activity or professionally) and mental health is still unclear, with earlier studies reporting contrasting findings. Here we tested whether musical engagement predicts (1) a diagnosis of depression, anxiety, schizophrenia, bipolar or stress-related disorders based on nationwide patient registers or (2) self-reported depressive, burnout and schizotypal symptoms in 10,776 Swedish twins. Information was available on the years individuals played an instrument, including their start and stop date if applicable, and their level of achievement. Survival analyses were used to test the effect of musical engagement on the incidence of psychiatric disorders. Regression analyses were applied for self-reported psychiatric symptoms. Additionally, we conducted co-twin control analyses to further explore the association while controlling for genetic and shared environmental confounding. Results showed that overall individuals playing a musical instrument (independent of their musical achievement) may have a somewhat increased risk for mental health problems, though only significant for self-reported mental health measures. When controlling for familial liability associations diminished, suggesting that the association is likely not due to a causal negative effect of playing music, but rather to shared underlying environmental or genetic factors influencing both musicianship and mental health problems

The application of team flow theory

Despite the noted potential for ‘team flow’ to enhance a team’s effectiveness, productivity, performance, and capabilities, studies on the construct are scarce. Most research on flow has been conducted either at the individual level, which generally constitutes the experience of complete absorption while working on a task, or at the artistic ensemble level, which reflects a gestalt group experience. But, team flow in the work environment, where teams differ from performance groups, has not yet been studied or reported. One of the reasons for this is the difficulty applying theories of flow to the team level, because the research on flow, group flow, and team dynamics does not readily gel. In this chapter, however, we will briefly discuss the precursors and components of team flow and its consequences. We will also describe how these precursors and components work by giving some examples of team flow experiences in different environments. Our analysis provides both theoretical insights into the causes of the emergence of team flow and practical suggestions for work teams to foster team flow experiences

Vinflunine in the treatment of relapsed metastatic urothelial cancer: A systematic review and meta-analysis of real-world series

Background: Vinflunine (VFL) is approved in Europe as second-line treatment of metastatic urothelial cancer after failure of platinum-containing therapy. We performed a systematic review and meta-analysis of real-world data (RWD) to assess utilization, efficacy and safety of VFL. Methods: We performed a MEDLINE search for the period of 1/1/2000-31/8/2017. Full-length articles providing post-marketing RWD on VFL in patients failing previous chemotherapy were eligible. Interventional clinical trials were excluded. Results: Ten studies with 797 patients were identified. According to pooled REs analysis, overall response rate was 19%, most frequent, all-grade toxicities were fatigue (41%), constipation (39%), nausea/vomiting (25%), and most prevalent Grade 3–4 toxicities were neutropenia (13%), anaemia (9%), fatigue (8%). Median OS was comparable to results reported in recent randomized studies. Conclusion: Our findings confirm the efficacy and safety of VFL in an unselected population and support the use of VFL in the changing treatment paradigm of relapsed mUC. © 2019 Elsevier B.V