The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Psychological well-being and coping: the predictive value of adult attachment, dispositional mindfulness, and emotion regulation

The primary aim of this study was to examine the underlying relationship between adult attachment, dispositional mindfulness, and emotion regulation, and investigate how well these constructs can predict coping and well-being. A university sample of participants (n = 174) completed an online survey to assess attachment (anxiety, avoidance, disorganized), emotion regulation, dispositional mindfulness, coping behaviors, and psychological well-being. Exploratory factor analysis assessed the underlying relationship between measures of attachment, emotion regulation, and mindfulness, and presented a two-factor solution accounting for 47% of total variance across participant scores. Attachment, mindfulness, and emotion regulation subscales differentially loaded across the two factors. The first factor, “resilient mental functioning,” accounted for 33% of variance; the second factor, “disorganized emotional functioning,” accounted for 14% of total variance. These two extracted factors were used in subsequent mediation modeling to determine the effects of coping behaviors on the relationship between the extracted factors and six subscales of psychological well-being. Mediation analyses revealed that defeatism coping was a significant mediator in the relationship between resilient mental functioning and five of the psychological well-being scales and between disorganized emotional functioning and all six of these scales. The results add to the current understanding of the relationship between all three constructs and are the first to examine the construct of adult disorganized attachment and its possible role in the relationship between adult attachment and dispositional mindfulness, as well as its influence on emotion regulation

Silicon nanostructures for photonics and photovoltaics

Silicon has long been established as the material of choice for the microelectronics industry. This is not yet true in photonics, where the limited degrees of freedom in material design combined with the indirect bandgap are a major constraint. Recent developments, especially those enabled by nanoscale engineering of the electronic and photonic properties, are starting to change the picture, and some silicon nanostructures now approach or even exceed the performance of equivalent direct-bandgap materials. Focusing on two application areas, namely communications and photovoltaics, we review recent progress in silicon nanocrystals, nanowires and photonic crystals as key examples of functional nanostructures. We assess the state of the art in each field and highlight the challenges that need to be overcome to make silicon a truly high-performing photonic material