Adjuvant pazopanib does not PROTECT against recurrence of high risk initially localised renal cell cancer, but does provide novel insights

Improved post-surgical management of the 70% of all renal cell cancer (RCC) patients who present to urological surgeons with initially localised RCC, to prevent subsequent progression, is an area of great need within uro-oncology.GD Stewart has received educational grants from Pfizer and Intuitive Surgical; consultancy fees from Pfizer, EUSA Pharma and Cambridge Medical Robotics; Travel expenses from Pfizer and Speaker fees from Pfizer. RA Figlin has received research funding from Peloton, BMS, Argos Therapeutics, Exilexis, and Cerulean; consulting fees from Novartis, Pfizer, Nektar, Peloton, Calithera, and Acceleron. S Negrier reports honoraria from Pfizer, Novartis, EUSA Pharma, Ipsen Biotech and Bristol-Myers Squibb. BC Leibovich declares no conflicts of interest

Self-assembly around curved surfaces

We present a parametric study of self-assembled photonic crystal growth as a function of radius of curvature. To do this, we used a combination of microscope slides, glass capillaries and optical fibres as substrates to grow the self-assembled films on. Microscope and SEM images, as well as broadband transmission spectra were used to characterise the crystal, and the effect the changing surface curvature had on the crystal quality. Limitations for fabricating the crystals on highly curved surfaces will be presented

Different Successful Management Strategies for Obstructing Renal Parapelvic Cysts

Parapelvic cysts originate in the renal parenchyma and extend into the renal sinus. A series of 3 patients with symptomatic obstructing parapelvic cysts is described, 2 with acute presentations, and 1 with chronic symptoms. In 2 of the 3 cases, there was a significant delay in establishing a diagnosis. Although one individual was successfully managed by image-guided cyst aspiration, the second patient required repeated aspiration due to cyst re-accumulation. A high index of clinical suspicion and a combination of imaging modalities, including serial ultrasound, excretory-phase CT, and MAG3 renogram, are necessary to establish the diagnosis and monitor response to treatment

Identifying Boosted Objects with N-subjettiness

We introduce a new jet shape -- N-subjettiness -- designed to identify boosted hadronically-decaying objects like electroweak bosons and top quarks. Combined with a jet invariant mass cut, N-subjettiness is an effective discriminating variable for tagging boosted objects and rejecting the background of QCD jets with large invariant mass. In efficiency studies of boosted W bosons and top quarks, we find tagging efficiencies of 30% are achievable with fake rates of 1%. We also consider the discovery potential for new heavy resonances that decay to pairs of boosted objects, and find significant improvements are possible using N-subjettiness. In this way, N-subjettiness combines the advantages of jet shapes with the discriminating power seen in previous jet substructure algorithms.Comment: 26 pages, 26 figures, 2 tables; v2: references added; v3: discussion of results extende

What should be done with antisocial personality disorder in the new edition of the diagnostic and statistical manual of mental disorders (DSM-V)?

Antisocial personality disorder, psychopathy, dissocial personality disorder and sociopathy are constructs that have generally been used to predict recidivism and dangerousness, alongside being used to exclude patients from treatment services. However, 'antisocial personality disorder' has recently begun to emerge as a treatment diagnosis, a development reflected within cognitive behaviour therapy and mentalisation-based psychotherapy. Many of the behaviour characteristics of antisocial personality disorder are, at the same time, being targeted by interventions at criminal justice settings. A significantly higher proportion of published articles focusing on antisocial personality concern treatment when compared to articles on psychopathy. Currently, the proposal for antisocial personality disorder for the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, suggests a major change in the criteria for this disorder. While the present definition focuses mainly on observable behaviours, the proposed revision stresses interpersonal and emotional aspects of the disorder drawing on the concept of psychopathy. The present commentary suggests that developments leading to improvement in the diagnosis of this type of disorder should, rather than focusing exclusively on elements such as dangerousness and risk assessment, point us to ways in which patients can be treated for their problems

Immunotherapy for Renal Cancer: Sequencing and Combinations

Objective To evaluate ongoing trials of combinations including immunotherapy and sequencing of agents to treat RCC. Evidence acquisition Recent data and ongoing trials were analyzed to evaluate the direction of research in this arena. Evidence synthesis The favorable therapeutic index of programmed cell death 1/programmed death-ligand 1 inhibitors enable combinations of these agents. Multiple ongoing phase 3 trials are evaluating the first-line therapy of RCC using a combination of programmed cell death 1/programmed death-ligand 1 inhibitors with vascular endothelial growth factor inhibitors or cytotoxic T-lymphocyte-associated protein 4 inhibitors. The role of sequencing using single agent sunitinib and avelumab will be evaluated in a randomized phase 2 trial. The role of vaccine therapy remains unproven. The role of predictive biomarkers to select appropriate therapy requires a greater focus, given the multitude of possible therapies. Conclusions Therapy for RCC should be tailored based on both patient and tumor characteristics. Combination therapy and sequencing of single agents may both play roles and are currently undergoing clinical trial evaluation. Patient summary Combinations of immunotherapy with angiogenesis inhibitors are undergoing vigorous clinical trial evaluations. Sequencing of immunotherapy and antiangiogenic therapy is also undergoing investigation. Clinical trial participation is critically important to develop new drugs and combinations, and biomarkers to select therapy

A Decision Analysis Evaluating Screening for Kidney Cancer Using Focused Renal Ultrasound

Background Screening for renal cell carcinoma (RCC) has been identified as a key research priority; however, no randomised control trials have been performed. Value of information analysis can determine whether further research on this topic is of value. Objective To determine (1) whether current evidence suggests that screening is potentially cost effective and, if so, (2) in which age/sex groups, (3) identify evidence gaps, and (4) estimate the value of further research to close those gaps. Design, setting, and participants A decision model was developed evaluating screening in asymptomatic individuals in the UK. A National Health Service perspective was adopted. Intervention A single focused renal ultrasound scan compared with standard of care (no screening). Outcome measurements and statistical analysis Expected lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER), discounted at 3.5% per annum. Results and limitations Given a prevalence of RCC of 0.34% (0.18–0.54%), screening 60-yr-old men resulted in an ICER of £18 092/QALY (€22 843/QALY). Given a prevalence of RCC of 0.16% (0.08–0.25%), screening 60-yr-old women resulted in an ICER of £37 327/QALY (€47 129/QALY). In the one-way sensitivity analysis, the ICER was <£30 000/QALY as long as the prevalence of RCC was ≥0.25% for men and ≥0.2% for women at age 60 yr. Given the willingness to pay a threshold of £30 000/QALY (€37 878/QALY), the population-expected values of perfect information were £194 million (€244 million) and £97 million (€123 million) for 60-yr-old men and women, respectively. The expected value of perfect parameter information suggests that the prevalence of RCC and stage shift associated with screening are key research priorities. Conclusions Current evidence suggests that one-off screening of 60-yr-old men is potentially cost effective and that further research into this topic would be of value to society. Patient summary Economic modelling suggests that screening 60-yr-old men for kidney cancer using ultrasound may be a good use of resources and that further research on this topic should be performed

The genome of the sea anemone Actinia equina (L.): Meiotic toolkit genes and the question of sexual reproduction.

The beadlet anemone Actinia equina (L.) (Cnidaria: Anthozoa: Actiniaria: Actiniidae) is one of the most familiar organisms of the North European intertidal zone. Once considered a single, morphologically variable species across northern Europe, it is now recognised as one member of a variable species complex. Previous studies of distribution, aggression, allozymes and mitochondrial DNA suggest that the diversity in form and colour within A. equina may hide still unrecognised species diversity. To empower further study of A. equina population genetics and systematics, we sequenced (PacBio Sequel) the genome of a single A. equina individual to produce a high-quality genome assembly (contig N50 = 492,607 bp, 1485 contigs, number of protein coding genes = 47,671, 97% BUSCO completeness). There is debate as to whether A. equina reproduces solely asexually, since no reliable, consistent evidence of sexual reproduction has been found. To gain further insight, we examined the genome for evidence of a 'meiotic toolkit' - genes believed to be found consistently in sexually reproducing organisms - and demonstrate that the A. equina genome appears not to have this full complement. Additionally, Smudgeplot analysis, coupled with high haplotype diversity, indicates this genome assembly to be of ambiguous ploidy, suggesting that A. equina may not be diploid. The suggested polyploid nature of this species coupled with the deficiency in meiotic toolkit genes, indicates that further field and laboratory studies of this species is warranted to understand how this species reproduces and what role ploidy may play in speciation within this speciose genus

Explicit Model Checking of Very Large MDP using Partitioning and Secondary Storage

The applicability of model checking is hindered by the state space explosion problem in combination with limited amounts of main memory. To extend its reach, the large available capacities of secondary storage such as hard disks can be exploited. Due to the specific performance characteristics of secondary storage technologies, specialised algorithms are required. In this paper, we present a technique to use secondary storage for probabilistic model checking of Markov decision processes. It combines state space exploration based on partitioning with a block-iterative variant of value iteration over the same partitions for the analysis of probabilistic reachability and expected-reward properties. A sparse matrix-like representation is used to store partitions on secondary storage in a compact format. All file accesses are sequential, and compression can be used without affecting runtime. The technique has been implemented within the Modest Toolset. We evaluate its performance on several benchmark models of up to 3.5 billion states. In the analysis of time-bounded properties on real-time models, our method neutralises the state space explosion induced by the time bound in its entirety.Comment: The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-24953-7_1