Help seeking for cancer 'alarm' symptoms: a qualitative interview study of primary care patients in the UK.

Delay in help seeking for cancer 'alarm' symptoms has been identified as a contributor to delayed diagnosis

Evidence for non-stellar rest-frame near-IR emission associated with increased star formation in galaxies at z∼1z \sim 1

We explore the presence of non-stellar rest-frame near-IR ($2-5 \ \mu \mathrm{m}$) emission in galaxies at $z \sim 1$. Previous studies identified this excess in relatively small samples and suggested that such non-stellar emission, which could be linked to the $3.3 \ \mu \mathrm{m}$ polycyclic aromatic hydrocarbons feature or hot dust emission, is associated with an increased star formation rate (SFR). In this Letter, we confirm and quantify the presence of an IR excess in a significant fraction of galaxies in the 3D-HST GOODS catalogs. By constructing a matched sample of galaxies with and without strong non-stellar near-IR emission, we find that galaxies with such emission are predominantly star-forming galaxies. Moreover, star-forming galaxies with an excess show increased mid- and far-IR and H$\alpha$ emission compared to other star-forming galaxies without. While galaxies with a near-IR excess show a larger fraction of individually detected X-ray active galactic nuclei (AGNs), an X-ray stacking analysis, together with the IR-colors and H$\alpha$ profiles, shows that AGNs are unlikely to be the dominant source of the excess in the majority of galaxies. Our results suggest that non-stellar near-IR emission is linked to increased SFRs and is ubiquitous among star-forming galaxies. As such, the near-IR emission might be a powerful tool to measure SFRs in the era of the James Webb Space Telescope.Comment: 6 pages, 5 figures, accepted for publication in ApJ

Environmentally Sustainable Construction: knowledge and learning in London planning departments

Environmentally sustainable construction is now recognised as a significant element of the broader sustainable development agenda and planners are being called upon to play a role in delivering more sustainable patterns of construction and development. This puts particular demands on the knowledge resources of planners since knowledge is implicated in the power relations between planners and developers. This paper examines the interrelationship between knowledge of environmentally sustainable construction and practice in planning departments. Drawing on a survey of and interviews with planners in London, it discusses the construction of knowledge within the dynamics of planning organisations and the potential for learning to promote a more sustainable built environment. Wenger's concept of communities of practice frames the analysis, alongside consideration of the translation of knowledge into bureaucratic and usable forms and the role of knowledge brokers in this process

Macroscopic Equations of Motion for Two Phase Flow in Porous Media

The established macroscopic equations of motion for two phase immiscible displacement in porous media are known to be physically incomplete because they do not contain the surface tension and surface areas governing capillary phenomena. Therefore a more general system of macroscopic equations is derived here which incorporates the spatiotemporal variation of interfacial energies. These equations are based on the theory of mixtures in macroscopic continuum mechanics. They include wetting phenomena through surface tensions instead of the traditional use of capillary pressure functions. Relative permeabilities can be identified in this approach which exhibit a complex dependence on the state variables. A capillary pressure function can be identified in equilibrium which shows the qualitative saturation dependence known from experiment. In addition the new equations allow to describe the spatiotemporal changes of residual saturations during immiscible displacement.Comment: 15 pages, Phys. Rev. E (1998), in prin

Differential expression analysis for sequence count data

*Motivation:* High-throughput nucleotide sequencing provides quantitative readouts in assays for RNA expression (RNA-Seq), protein-DNA binding (ChIP-Seq) or cell counting (barcode sequencing). Statistical inference of differential signal in such data requires estimation of their variability throughout the dynamic range. When the number of replicates is small, error modelling is needed to achieve statistical power.

*Results:* We propose an error model that uses the negative binomial distribution, with variance and mean linked by local regression, to model the null distribution of the count data. The method controls type-I error and provides good detection power. 

*Availability:* A free open-source R software package, _DESeq_, is available from the Bioconductor project and from "http://www-huber.embl.de/users/anders/DESeq":http://www-huber.embl.de/users/anders/DESeq

Quality of compounded hydrocortisone capsules used in the treatment of children.

Objectives: Due to the lack of paediatric licensed formulations, children are often treated with individualized pharmacy-compounded adult medication. An international web-based survey about the types of medication in children with adrenal insufficiency (AI) revealed that the majority of paediatric physicians are using pharmacy-compounded medication to treat children with AI. Observations of loss of therapy control in children with congenital adrenal hyperplasia with compounded hydrocortisone capsules and regained control after prescribing a new hydrocortisone batch led to this "real world" evaluation of pharmacy-compounded paediatric hydrocortisone capsules. Methods: Capsule samples were collected randomly from volunteering parents of treated children suffering from congenital adrenal hyperplasia from all over Germany. Analysis of net mass and hydrocortisone content by HPLC-UV (high performance liquid chromatography) method were performed based on the European Pharmacopeia. Results: In total 61 batches were sent in. 5 batches could not be analyzed because of missing dose information, insufficient number of capsules or were not possible to be evaluated. 56 batches containing 1125 capsules were evaluated. 21.4% of the batches revealed insufficiency in uniformity of net mass or drug content and additional 3.6% failed because they did not contain the labelled drug. Conclusions: Compounded medication is a possible cause of variation of steroid doses in children with adrenal insufficiency or congenital adrenal hyperplasia, putting these vulnerable patients at risk of poor disease control and adrenal crisis. These data may apply to other individualized compounded oral medication as well, emphasizing the need for development of licensed paediatric formulations approved by regulatory authorities

Sibling bullying at 12 years and high-risk behavior in early adulthood : a prospective cohort study

Emerging evidence suggests that sibling aggression is associated with the development of high‐risk behavior. This study investigated the relationship between sibling bullying perpetration and victimization in early adolescence and high‐risk behavior in early adulthood. Sibling bullying was assessed at 12 years in 6,988 individuals from the Avon Longitudinal Study of Parents and Children, a birth cohort based in the UK and high‐risk behavioral outcomes were assessed at 18–20 years. Frequent sibling bullying perpetration predicted antisocial behavior (OR = 1.74; 95%CI, 1.38–2.20), while frequent sibling bullying victimization increased the odds of nicotine dependence (OR = 2.87; 95%CI, 1.55–5.29), even after accounting for peer bullying and parent maltreatment. Categorical analysis revealed that particularly bullies and bully‐victims were at risk of developing high‐risk behavior. Finally, this study found that adolescents who were involved in bullying perpetration across multiple contexts (home and school) had the highest odds of reporting antisocial behavior (OR = 3.05; 95%CI, 2.09–4.44), criminal involvement (OR = 2.12; 95%CI, 1.23–3.66), and illicit drug use (OR = 2.11; 95%CI, 1.44–3.08). Findings from this study suggest that sibling bullying perpetration may be a marker of or a contributory factor along the developmental trajectory to antisocial behavior problems. Intervention studies are needed in order to test whether reducing sibling bullying can alleviate long‐term adverse social and behavioral outcomes

Co-targeting PIM and PI3K/mTOR using multikinase inhibitor AUM302 and a combination of AZD-1208 and BEZ235 in prostate cancer

PIM and PI3K/mTOR pathways are often dysregulated in prostate cancer, and may lead to decreased survival, increased metastasis and invasion. The pathways are heavily interconnected and act on a variety of common efectors that can lead to the development of resistance to drug inhibitors. Most current treatments exhibit issues with toxicity and resistance. We investigated the novel multikinase PIM/PI3K/mTOR inhibitor, AUM302, versus a combination of the PIM inhibitor, AZD-1208, and the PI3K/mTOR inhibitor BEZ235 (Dactolisib) to determine their impact on mRNA and phosphoprotein expression, as well as their functional efcacy. We have determined that around 20% of prostate cancer patients overexpress the direct targets of these drugs, and this cohort are more likely to have a high Gleason grade tumour (≥Gleason 8). A co-targeted inhibition approach ofered broader inhibition of genes and phosphoproteins in the PI3K/mTOR pathway, when compared to single kinase inhibition. The preclinical inhibitor AUM302, used at a lower dose, elicited a comparable or superior functional outcome compared with combined AZD-1208 +BEZ235, which have been investigated in clinical trials, and could help to reduce treatment toxicity in future trials. We believe that a co-targeting approach is a viable therapeutic strategy that should be developed further in pre-clinical studies