Summary The Cancer Genome Atlas (TCGA) project has analyzed mRNA expression, miRNA expression, promoter methylation, and DNA copy number in 489 high-grade serous ovarian adenocarcinomas (HGS-OvCa) and the DNA sequences of exons from coding genes in 316 of these tumors. These results show that HGS-OvCa is characterized by TP53 mutations in almost all tumors (96%); low prevalence but statistically recurrent somatic mutations in 9 additional genes including NF1, BRCA1, BRCA2, RB1, and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three miRNA subtypes, four promoter methylation subtypes, a transcriptional signature associated with survival duration and shed new light on the impact on survival of tumors with BRCA1/2 and CCNE1 aberrations. Pathway analyses suggested that homologous recombination is defective in about half of tumors, and that Notch and FOXM1 signaling are involved in serous ovarian cancer pathophysiology.

BackgroundAnorexia nervosa (AN) is a serious disorder incurring high costs due to hospitalization. International treatments vary, with prolonged hospitalizations in Europe and shorter hospitalizations in the USA. Uncontrolled studies suggest that longer initial hospitalizations that normalize weight produce better outcomes and fewer admissions than shorter hospitalizations with lower discharge weights. This study aimed to compare the effectiveness of hospitalization for weight restoration (WR) to medical stabilization (MS) in adolescent AN.MethodWe performed a randomized controlled trial (RCT) with 82 adolescents, aged 12–18 years, with a DSM-IV diagnosis of AN and medical instability, admitted to two pediatric units in Australia. Participants were randomized to shorter hospitalization for MS or longer hospitalization for WR to 90% expected body weight (EBW) for gender, age and height, both followed by 20 sessions of out-patient, manualized family-based treatment (FBT).ResultsThe primary outcome was the number of hospital days, following initial admission, at the 12-month follow-up. Secondary outcomes were the total number of hospital days used up to 12 months and full remission, defined as healthy weight (>95% EBW) and a global Eating Disorder Examination (EDE) score within 1 standard deviation (s.d.) of published means. There was no significant difference between groups in hospital days following initial admission. There were significantly more total hospital days used and post-protocol FBT sessions in the WR group. There were no moderators of primary outcome but participants with higher eating psychopathology and compulsive features reported better clinical outcomes in the MS group.ConclusionsOutcomes are similar with hospitalizations for MS or WR when combined with FBT. Cost savings would result from combining shorter hospitalization with FBT.

We have designed and implemented a practical nanoelectronic interface to G-protein coupled receptors (GPCRs), a large family of membrane proteins whose roles in the detection of molecules outside eukaryotic cells make them important pharmaceutical targets. Specifically, we have coupled olfactory receptor proteins (ORs) with carbon nanotube transistors. The resulting devices transduce signals associated with odorant binding to ORs in the gas phase under ambient conditions and show responses that are in excellent agreement with results from established assays for OR–ligand binding. The work represents significant progress on a path toward a bioelectronic nose that can be directly compared to biological olfactory systems as well as a general method for the study of GPCR function in multiple domains using electronic readout.

Objective: Although cancer care guidelines recommend screening for distress among cancer patients and offering psychological support when indicated, many patients decline offers of such support. This study aimed to quantify uptake and adherence to psychological support and to identify predictors of each.Methods: Searches were conducted in Embase, Medline, PsychInfo and Scopus to identify studies reporting uptake or adherence rates for individual psychological interventions targeting distress, anxiety or depression for cancer patients or survivors.Results: Across the 53 included studies reporting uptake and/or adherence rates for 12 323 cancer patients, the uptake and adherence rates were 60.1% and 90.4%, respectively. Patients screened and identified as distressed were less likely to accept intervention than unselected patients (50.3% compared with 66.3%, Q(1) = 4.66, P = 0.031). Uptake of therapy was higher for interventions delivered by telephone rather than face-to-face (71.2% compared with 53.8%, Q(1) = 4.91, P = 0.027) and when therapy was offered prior to medical treatment compared with later (72.9% compared with 56.8%, Q (1) = 5.60, P = 0.018). Patients were more likely to accept intervention from nurses than other allied health professionals (68.3% compared with 50.5%, Q(1) = 5.76, P = 0.016).Conclusions: Patients appeared more receptive to interventions offered near diagnosis, over the telephone and by nurses. Although this suggests higher acceptability of such interventions, evidence of their greater efficacy is lacking, and this merits further investigation. Research is needed to understand barriers to acceptance of psychological support, particularly because uptake rates were lower for distressed patients.

Integration of synaptic input in dendritic trees is a nonlinear process in which excitatory input may elicit spikes localized within the branch receiving input. In addition to membrane current-driven events, a type of dendritic spike has recently been described that instead depends on NMDA receptor current. These NMDA spikes enable superlinear integration among inputs targeted close together on a single branch. Here a compartment model of a layer 5 pyramidal cell was used to examine the mechanisms underlying NMDA spikes and to test properties not directly accessible experimentally. The results indicate the following: initiation of an NMDA spike in a tertiary dendrite in 1 mM [Mg 2ϩ ] requires an NMDA conductance density equivalent to 6 -8 nS within a 25-m-long dendritic subsegment; dendritic membrane currents are not required for NMDA spike production; and targeted dendritic (but not somatic) inhibitory input is exquisitely suited to veto an NMDA spike if it arrives within a 30 ms window in time. Finally, an analysis of the spatial density of NMDA conductance required for NMDA spike production implies that, at least up to the age (postnatal day 35) that these events have been observed, most of the excitatory synaptic conductance arriving at pyramidal cells is NMDA mediated.