Explore the vast range of titles available.

Background Continuing symptoms and poor health following cancer treatments may alter meaning in life for cancer survivors. Gynecologic cancer survivors are particularly troubled with physical sequelae. In addition, for the most common sites of disease, such as breast and gynecologic cancers, the prevalence of depression is also high. Purpose This study tests meaning in life as a mechanism for the relationship between physical symptoms and depressive symptoms. Methods Gynecologic cancer survivors ( N  = 260) participated. Measures of physical sequelae (nurse rated symptoms/signs, patient-reported gynecologic symptoms), meaning in life (harmony, life purpose, spirituality, and conversely, confusion and loss), and depressive symptoms were obtained at the time of a routine clinical follow-up visit 2–10 years following the completion of treatment. Latent variables were defined, and structural equation modeling tested a mediator model. Results Analyses support partial mediation. That is, survivors with more physical sequelae also reported lower levels of meaning in life, which was associated with higher levels of depressive symptoms. Conclusions Gynecologic cancer patients have been neglected in psychosocial research, and findings highlight the importance of existential issues in their lives. While many adjust well, those with persistent physical functioning deficits may experience depressive symptoms. By appreciating the role of meaning in their experience, we may help survivors foster their own growth and perspectives important for their future.

IntroductionThe human cost of cancer is staggering. Worldwide there were 10.9 million new cases, 6.7 million deaths and 24.6 million persons alive with cancer (within three years of diagnosis; Parkin et al., 2005). In many countries cancer is the second leading cause of death, only outnumbered by heart disease. In the United States, it has been the leading cause of death for persons younger than 85 since 1999, and over 1 million new cancer cases and almost 600 000 deaths are expected in 2005 (Jemal et al., 2005). However, there is striking variation across geographic locations. Research on the psychological and behavioural aspects of oncology began in the early 1950s; however, significant expansion has occurred in the last 25 years. This research has clarified biobehavioural factors in illness (Andersen et al., 1994), including relations between psychological responses and factors (e.g. personality, mood, coping style) and behavioural variables (e.g. compliance with treatment, diet, exercise), with more recent research incorporating biologic systems (e.g. immune and endocrine) and examining the interaction of these variables and their relationship to disease course (Andersen et al., 2004).This chapter provides a brief overview of the central findings which have emerged on the psychological and behavioural aspects of cancer. Other chapters in this volume can be consulted for site-specific findings. By way of introduction, we will begin with data on cancer incidence, death rates and gender differences.

Phase 1 studies have shown potential benefit of gene replacement in RPE65-mediated inherited retinal dystrophy. This phase 3 study assessed the efficacy and safety of voretigene neparvovec in participants whose inherited retinal dystrophy would otherwise progress to complete blindness. In this open-label, randomised, controlled phase 3 trial done at two sites in the USA, individuals aged 3 years or older with, in each eye, best corrected visual acuity of 20/60 or worse, or visual field less than 20 degrees in any meridian, or both, with confirmed genetic diagnosis of biallelic RPE65 mutations, sufficient viable retina, and ability to perform standardised multi-luminance mobility testing (MLMT) within the luminance range evaluated, were eligible. Participants were randomly assigned (2:1) to intervention or control using a permuted block design, stratified by age (<10 years and ≥10 years) and baseline mobility testing passing level (pass at ≥125 lux vs <125 lux). Graders assessing primary outcome were masked to treatment group. Intervention was bilateral, subretinal injection of 1·5 × 1011 vector genomes of voretigene neparvovec in 0·3 mL total volume. The primary efficacy endpoint was 1-year change in MLMT performance, measuring functional vision at specified light levels. The intention-to-treat (ITT) and modified ITT populations were included in primary and safety analyses. This trial is registered with ClinicalTrials.gov, number NCT00999609, and enrolment is complete. Between Nov 15, 2012, and Nov 21, 2013, 31 individuals were enrolled and randomly assigned to intervention (n=21) or control (n=10). One participant from each group withdrew after consent, before intervention, leaving an mITT population of 20 intervention and nine control participants. At 1 year, mean bilateral MLMT change score was 1·8 (SD 1·1) light levels in the intervention group versus 0·2 (1·0) in the control group (difference of 1·6, 95% CI 0·72–2·41, p=0·0013). 13 (65%) of 20 intervention participants, but no control participants, passed MLMT at the lowest luminance level tested (1 lux), demonstrating maximum possible improvement. No product-related serious adverse events or deleterious immune responses occurred. Two intervention participants, one with a pre-existing complex seizure disorder and another who experienced oral surgery complications, had serious adverse events unrelated to study participation. Most ocular events were mild in severity. Voretigene neparvovec gene replacement improved functional vision in RPE65-mediated inherited retinal dystrophy previously medically untreatable. Spark Therapeutics.

Breakthroughs in battery research are imperative to provide society with batteries that are safe and sustainable, have a high energy density, and have a long cycle life at low cost. Recent advances in research methodologies, the emergence of new market opportunities, and strategic funding schemes have allowed not only large, but also small companies, universities, and public research organizations to play an increasingly significant role in the advancement of battery technology. Challenges in battery technology development are multifaceted; therefore, a collaborative approach is crucial to bring together various stakeholders and ensure access to the full range of technical and scientific expertise. To grasp the core properties of electrode materials, electrolytes, and interfaces and to identify the mechanisms of battery degradation and failure, a multidisciplinary analytical approach is crucial. This strategy relies on the unique and complementary potential of advanced characterization techniques available at synchrotron and x-ray free electron laser facilities. Science-to-industry interactions are expected to increase the development of new standardized setups to approach realistic operando conditions. Therefore, rapid access to instruments, including high-throughput ex-situ , in-situ and operando capabilities, is key to accelerating the development of safe and sustainable batteries. The purpose of this paper is to discuss how the characterization needs of the battery community can be met by establishing a collaboration network based on a meta-infrastructure model, where the emphasis will be on collaboration and the sharing of experience and data. The proposed methodology considers the urgency in the battery community and the necessary technical developments to reach the scope of collaboration and focuses in particular on the needs for standardization, big data challenges, and open data approaches.

Summary Purpose This phase I study evaluated the safety, tolerability, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of tivantinib combined with sorafenib in patients with advanced solid tumors. Materials and Methods A standard 3 + 3 dose escalation design was used. At the RP2D, expansion cohorts in 5 tumor types could be enrolled. Pharmacogenetic and pharmacodynamic analysis were performed. Results Eighty-seven patients received the study treatment. The combination had no unexpected toxicities. The most common treatment-related adverse events (AE) were rash (40 %), diarrhea (38 %), and anorexia (33 %). The RP2D was tivantinib 360 mg BID and sorafenib 400 mg BID for all cancer histologies, except in hepatocellular carcinoma (HCC) patients tivantinib was 240 mg BID plus sorafenib 400 mg BID. The overall response rate was 12 % in all patients, 26 % in melanoma, 15 % in renal cell carcinoma (RCC), 10 % in HCC, and 0 % in other patients. Disease control rate (CR, PR and SD ≥8 weeks) was 58 % in all patients, 90 % in RCC, 65 % in HCC, 63 % in melanoma, 40 % in breast cancer, and 8 % in NSCLC patients. Conclusions The combination treatment could be administered at full standard single-agent doses in all patients except those with HCC, where tivantinib was lowered to 240 mg BID. Preliminary evidence of anticancer activity was observed in patients with RCC, HCC, and melanoma, including patients refractory to sorafenib and/or other anti-VEGF pathway therapies. The combination treatment has therapeutic potential in treating a variety of solid tumors.