A hot and fast ultra-stripped supernova that likely formed a compact neutron star binary.

Compact neutron star binary systems are produced from binary massive stars through stellar evolution involving up to two supernova explosions. The final stages in the formation of these systems have not been directly observed. We report the discovery of iPTF 14gqr (SN 2014ft), a type Ic supernova with a fast-evolving light curve indicating an extremely low ejecta mass (≈0.2 solar masses) and low kinetic energy (≈2 × 1050 ergs). Early photometry and spectroscopy reveal evidence of shock cooling of an extended helium-rich envelope, likely ejected in an intense pre-explosion mass-loss episode of the progenitor. Taken together, we interpret iPTF 14gqr as evidence for ultra-stripped supernovae that form neutron stars in compact binary systems.

Differentiating short- and long-term effects of diet in the obese mouse using (1) H-nuclear magnetic resonance metabolomics.

This study determined whether targeted metabolomic profiling of serum, using 1H nuclear magnetic resonance, could be employed to distinguish the effects of obesity from those of diet in mice. Following weaning, littermates were randomly divided into two diet groups: chow and high fat. After 12 weeks of dietary manipulation, fat-fed animals were obese and hyperglycaemic. Mice from each treatment either maintained their current diet or switched to the opposite diet for a final week. Differences in metabolite levels were determined using orthogonal projection to latent structures and cross-validated discriminant analysis. The short- and long-term effects of each diet could be clearly distinguished. Short-term diet effects are the major contributor to the metabolic profile, underscoring the need for controls beyond the standard fast before serum collection. This work shows the importance of dietary controls when attempting to isolate obesity-related changes and highlights the ability of metabolomics to identify subtle changes when experiments are properly structured.

Metabolomic profiling of dietary-induced insulin resistance in the high fat-fed C57BL/6J mouse.

The predictive ability of metabolic profiling to detect obesity-induced perturbations in metabolism has not been clearly established. Complex aetiologies interacting with environmental factors highlight the need to understand how specific manipulations alter metabolite profiles in this state. The aim of this study was to determine if targeted metabolomic profiling could be employed as a reliable tool to detect dietary-induced insulin resistance in a small subset of experimental animals (n = 10/treatment). Following weaning, male C57BL/6J littermates were randomly divided into two dietary groups: chow and high fat. Following 12 weeks of dietary manipulation, mice were fasted for 5 h prior to serum collection. The resultant high fat-fed animals were obese and insulin resistant as shown by a euglycaemic-hyperinsulinaemic clamp. Sera were analysed by proton nuclear magnetic resonance spectroscopy, and 46 known compounds were identified and quantified. Multivariate analysis by orthogonal partial least squares discriminant analysis, a projection method for class separation, was then used to establish models of each treatment. Models were able to predict class separation between diets with 90% accuracy. Variable importance plots revealed the most important metabolites in this discrimination to include lysine, glycine, citrate, leucine, suberate and acetate. These metabolites are involved in energy metabolism and may be representative of the perturbations taking place with insulin resistance. Results show metabolomics to reliably describe the metabolic effects of insulin resistance in a small subset of samples and are an initial step in establishing metabolomics as a tool to understand the biochemical signature of insulin resistance.

Development of bioinformatics resources for display and analysis of copy number and other structural variants in the human genome.

The discovery of an abundance of copy number variants (CNVs; gains and losses of DNA sequences >1 kb) and other structural variants in the human genome is influencing the way research and diagnostic analyses are being designed and interpreted. As such, comprehensive databases with the most relevant information will be critical to fully understand the results and have impact in a diverse range of disciplines ranging from molecular biology to clinical genetics. Here, we describe the development of bioinformatics resources to facilitate these studies. The Database of Genomic Variants (http://projects.tcag.ca/variation/) is a comprehensive catalogue of structural variation in the human genome. The database currently contains 1,267 regions reported to contain copy number variation or inversions in apparently healthy human cases. We describe the current contents of the database and how it can serve as a resource for interpretation of array comparative genomic hybridization (array CGH) and other DNA copy imbalance data. We also present the structure of the database, which was built using a new data modeling methodology termed Cross-Referenced Tables (XRT). This is a generic and easy-to-use platform, which is strong in handling textual data and complex relationships. Web-based presentation tools have been built allowing publication of XRT data to the web immediately along with rapid sharing of files with other databases and genome browsers. We also describe a novel tool named eFISH (electronic fluorescence in situ hybridization) (http://projects.tcag.ca/efish/), a BLAST-based program that was developed to facilitate the choice of appropriate clones for FISH and CGH experiments, as well as interpretation of results in which genomic DNA probes are used in hybridization-based experiments.

Environmental factors and not genotype influence the plasma level of interleukin-1 receptor antagonist in normal individuals.

Cytokine production may be regulated by both genotypic (single nucleotide or tandem repeat polymorphisms) and non-genotypic factors relating to the environment and inherent biology (i.e. gender). Interleukin (IL)-1 is one of the body's most highly proinflammatory cytokines and is implicated in the pathophysiology of numerous diseases, but also in the maintenance of homeostasis in a number of tissues. The cytokine IL-1 receptor antagonist (IL-1Ra) is the competitive inhibitor of the IL-1 agonists IL-1alpha and IL-1beta. In vivo IL-1Ra was measured in a cohort of 200 + blood donors and the effect of the IL-1 gene polymorphisms, environmental and biological factors assessed. In this study, we observed that possession of particular alleles of 5 IL-1 gene polymorphisms (IL1A-889, IL1Alpha VNTR, IL1B -511, IL1B +3953 and the IL1RN VNTR) did not correlate with higher plasma IL-1Ra levels. Environmental factors such as smoking and non-steroidal anti-inflammatory drug ingestion were associated with higher in vivo IL-1Ra levels (P = 0.015 and 0.022, respectively), but biological factors such as gender, age and menstruation status did not have any impact upon in vivo IL-1Ra levels. Genotypic associations of IL-1 gene family polymorphisms with disease features may reflect characteristics of stressed rather than normal control circuits for cytokine production.

Assessment of depression in older adult males by general practitioners. Ageism, physical problems and treatment.

BACKGROUND: Depressive symptoms are common among older people. This study evaluated whether the combination of age and the presence of a physical illness would influence the recognition, treatment and further investigation by general practitioners of possible depression in older adult males. METHOD: A 2 x 2 factorial design involving four vignettes of a male with depression was used. The variables involved two age levels and the presence or absence of heart disease. The sample consisted of 189 Perth GPs. RESULT: Depression was recognised by up to 95% of the GPs. Although the recognition of uncomplicated depressive symptoms was lower in the 76 year old male compared with the 56 year old, health recognition seemed the same for both. There were no effects for recommended treatment, prognosis, perceived competency to treat or further investigation. Antidepressant medication and counselling by the GP were the recommended treatments. CONCLUSION: Depressive symptoms were recognised by more GPs in this study than in the existing literature, but with less likelihood of recognition for the older male.

Interleaving reading and acting while following procedural instructions.

Memory for an interactive procedure acquired from written instructions is improved if the procedure can be carried out while the instructions are being read. The size of the read-act cycle was manipulated in Experiments 1 and 2 by comparing chunked instruction-following, in which 3 or 4 steps are read then performed with single-step conditions. In both experiments, enforced chunking improved subsequent unaided performance of the procedure. In Experiment 3, participants were allowed to manage the interleaving of reading and acting. The imposition of a small behavioral cost (a single mouse point-and-click operation) on the switch between instructions and device encouraged more chunking and better subsequent test performance. The authors concluded that the interleaving of reading and acting is an important practical concern in the design of interactive procedures and that more effective chunk-based strategies can quite readily be encouraged.

Rapid hematopoietic recovery after multicycle high-dose chemotherapy: enhancement of filgrastim-induced progenitor-cell mobilization by recombinant human stem-cell factor.

PURPOSE: To assess the mobilization potential and safety of recombinant human stem-cell factor (SCF) when coadministered with filgrastim to untreated women with poor-prognosis breast cancer. PATIENTS AND METHODS: Eligible women had breast cancer with 10 or more positive axillary nodes, or estrogen receptor-negative tumor with 4 positive nodes, or stage III disease. Patients were randomized to receive SCF plus filgrastim or filgrastim alone. Filgrastim 12 microg/kg daily was administered for 6 days by continuous subcutaneous infusion. SCF was administered by daily subcutaneous injection at 5, 10, or 15 microg/kg concurrent with filgrastim for 7 days, or 10 microg/kg daily starting 3 days before filgrastim for a total of 10 days (SCF pretreatment). Apheresis was performed on days 5, 6, and 7 of filgrastim administration. Patients then had three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2 every 28 days, each supported by one third of the apheresis product. RESULTS: Sixty-two women were treated. Greater yields occurred in patients who received SCF 10 microg/kg daily plus filgastim than those who received filgrastim alone (P=.013 for CD34+ cells; P=.07 for granulocyte-macrophage colony-forming cells [GM-CFCs]). The difference was more marked with SCF-pretreatment than concurrent SCF. Fewer aphereses were required to reach the predetermined target of peripheral-blood progenitor/stem cells (PBPCs) in women who received SCF. SCF was generally well tolerated. Hematologic recovery was rapid after each of the three cycles of chemotherapy. There was no difference in recovery between the different treatment groups. CONCLUSION: Mobilization of PBPCs by filgrastim is significantly enhanced by coadministration of SCF, and commencing SCF before filgrastim can optimize this effect. SCF has the potential to reduce the number of aphereses required to collect a target number of PBPCs.

Comparative study of the pharmacokinetics and toxicity of high-dose epirubicin with or without dexrazoxane in patients with advanced malignancy.

PURPOSE: We evaluated the toxicity and pharmacokinetics of the combination of dexrazoxane with epirubicin at dexrazoxane/epirubicin dose ratios of 5 to 9:1 in a controlled, crossover phase I study in patients with advanced malignancy. PATIENTS AND METHODS: Thirty-eight patients with a variety of malignancies were enrolled. Assessable patients received two cycles of chemotherapy consisting of epirubicin alone and in combination with dexrazoxane. Comparisons were made between the toxicity and pharmacokinetics of epirubicin in the two treatment arms, using each patient as his or her own control. Dexrazoxane and epirubicin were delivered at dose levels of 600/120 mg/m2, 900/120 mg/m2, 900/135 mg/m2, 900/150 mg/m2, and 1,200/135 mg/m2, respectively. Twenty-six patients completed two cycles of chemotherapy and were therefore assessable. RESULTS: The maximum-tolerated doses (MTDs) of dexrazoxane/epirubicin were 1,200/135 mg/m2, with the dose-limiting toxicities being neutropenia, infection, and stomatitis. There was no difference in the nadir neutrophil or platelet counts between single-agent and combination treatment at any of the dose levels. Severe vomiting and stomatitis occurred less frequently following administration of epirubicin and dexrazoxane when compared with epirubicin alone (P = .01 and .02, respectively). Prior administration of higher doses (900 mg/m2 and 1,200 mg/m2) of dexrazoxane increased the systemic clearance of epirubicin, resulting in a decrease in the area under the curve (AUC). Elimination half-life, maximum plasma concentration (Cmax), and apparent volume of distribution of epirubicin were not significantly affected by dexrazoxane. Left ventricular ejection fraction (LVEF) decreased by greater than 10% in two patients, but neither developed clinical or radiologic evidence of cardiac failure. CONCLUSION: This study demonstrates that dexrazoxane can be safely combined with escalating doses of epirubicin at dose ratios of 5 to 9:1 without having an adverse impact on toxicity. Studies are need to determine the optimal dose ratio for cardioprotection and to explore further the pharmacokinetic interactions of the two drugs at increasing doses of epirubicin supported by hematopoietic growth factors.

Randomized study of the effect of midnight removal of urinary catheters.

This study shows that removal of urinary catheters at midnight has several advantages over removal at 6 AM. The midnight group had a significantly greater initial voided volume and a longer time to first void than the equivalent 6 AM group. Advantages to midnight catheter removal also exist for nursing staff. Midnight tends to be less busy on the nursing unit compared with 6 AM, thus making it a preferable time for performance of routine tasks. Catheter removal at midnight also allows for convenient observation of patient voiding and assessment earlier in the day. This means that any necessary intervention can take place during working hours when more staff are on duty. There is also the potential for earlier discharge, with economic benefits related to shorter bed stay and more efficient discharge planning. We believe midnight catheter removal offers considerable benefits over the traditional 6 AM time on both general and urology units.

Randomised study of the effect of midnight versus 0600 removal of urinary catheters.

A randomised controlled trial was undertaken to determine the effects of midnight removal of urinary catheters on patients' voiding patterns and subsequent discharge from hospital. Patients whose urinary catheters were removed at midnight showed a greater volume of initial void than those whose catheters were removed at the usual time of 0600. Removal of urinary catheters routinely at midnight permits earlier assessment of patients' voiding, which may allow for earlier discharge from hospital.