The Ammount of Interstellar Carbon Locked in Solid Hydrogenated Amorphous Carbon

We review the literature and present new experimental data to determine the amount of carbon likely to be locked in form of solid hydrogenated amorphous carbon (HAC) grains. We conclude on the basis of a thorough analysis of the intrinsic strength of the C-H stretching band at 3.4 micron that between 10 and 80 ppM H of carbon is in the form of HAC grains. We show that it is necessary to know the level of hydrogenation (H/C) of the interstellar HAC to determine more precisely the amount of carbon it ties up. We present optical constants, photoluminescence spectroscopy, and IR absorption spectroscopy for a particular HAC sample that is shown to have a 3.4 micron absorption feature that is quantatively consistent with that observed in the diffuse interstellar medium.Comment: This paper is 14 pages long with 5 figures and will appear in the 1 December 1999 issue of Ap

Randomized double-blind trial of pregabalin versus placebo in conjunction with palliative radiotherapy for cancer-induced bone pain

Purpose Cancer-induced bone pain (CIBP) affects one third of patients with cancer. Radiotherapy remains the gold-standard treatment; however, laboratory and clinical work suggest that pregabalin may be useful in treating CIBP. The aim of this study was to examine pregabalin in patients with CIBP receiving radiotherapy. Patients and Methods A multicenter, double-blind randomized trial of pregabalin versus placebo was conducted. Eligible patients were age ≥ 18 years, had radiologically proven bone metastases, were scheduled to receive radiotherapy, and had pain scores ≥ 4 of 10 (on 0-to-10 numeric rating scale). Before radiotherapy, baseline assessments were completed, followed by random assignment. Doses of pregabalin and placebo were increased over 4 weeks. The primary end point was treatment response, defined as a reduction of ≥ 2 points in worst pain by week 4, accompanied by a stable or reduced opioid dose, compared with baseline. Secondary end points assessed average pain, interference of pain with activity, breakthrough pain, mood, quality of life, and adverse events. Results A total of 233 patients were randomly assigned: 117 to placebo and 116 to pregabalin. The most common cancers were prostate (n = 88; 38%), breast (n = 77; 33%), and lung (n = 42; 18%). In the pregabalin arm, 45 patients (38.8%) achieved the primary end point, compared with 47 (40.2%) in the placebo arm (adjusted odds ratio, 1.07; 95% CI, 0.63 to 1.81; P = .816). There were no statistically significant differences in average pain, pain interference, or quality of life between arms. There were differences in mood (P = .031) and breakthrough pain duration (P = .037) between arms. Outcomes were compared at 4 weeks. Conclusion Our findings do not support the role of pregabalin in patients with CIBP receiving radiotherapy. The role of pregabalin in CIBP with a clinical neuropathic pain component is unknown

Photochemical versus Thermal Synthesis of Cobalt Oxyhydroxide Nanocrystals

Photochemical methods facilitate the generation, isolation, and study of metastable nanomaterials having unusual size, composition, and morphology. These harder-to-isolate and highly reactive phases, inaccessible using conventional high-temperature pyrolysis, are likely to possess enhanced and unprecedented chemical, electromagnetic, and catalytic properties. We report a fast, low-temperature and scalable photochemical route to synthesize very small (~3 nm) monodisperse cobalt oxyhydroxide (Co(O)OH) nanocrystals. This method uses readily and commercially available pentaamminechlorocobalt(III) chloride, [Co(NH3) 5Cl]Cl2, under acidic or neutral pH and proceeds under either near-UV (350 nm) or Vis (575 nm) illumination. Control experiments showed that the reaction proceeds at competent rates only in the presence of light, does not involve a free radical mechanism, is insensitive to O 2, and proceeds in two steps: (1) Aquation of [Co(NH3) 5Cl] 2+ to yield [Co(NH3) 5(H2O)] 3+, followed by (2) slow photoinduced release of NH3 from the aqua complex. This reaction is slow enough for Co(O)OH to form but fast enough so that nanocrystals are small (ca. 3 nm). The alternative dark thermal reaction proceeds much more slowly and produces much larger (~250 nm) polydisperse Co(O)OH aggregates. UV-Vis absorption measurements and ab initio calculations yield a Co(O)OH band gap of 1.7 eV. Fast thermal annealing of Co(O)OH nanocrystals leads to Co3O4 nanocrystals with overall retention of nanoparticle size and morphology. Thermogravimetric analysis shows that oxyhydroxide to mixed-oxide phase transition occurs at significantly lower temperatures (up to T = 64 degrees C) for small nanocrystals compared with the bulk

Gonadotropin-releasing hormone analogs during chemotherapy for preservation of ovarian function and fertility in premenopausal early breast cancer patients: a systematic review and meta-analysis of individual patient-level data

Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial. This systematic review and meta-analysis using individual patient\u2013level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer. Methods The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Primary end points were premature ovarian insufficiency (POI) rate and post-treatment pregnancy rate. Disease-free survival and overall survival were secondary end points. Because each study represents a cluster, statistical analyses were performed using a random effects model. Results A total of 873 patients from five trials were included. POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted odds ratio, 0.38; 95% CI, 0.26 to 0.57; P, .001). A total of 37 (10.3%) patients had at least one post-treatment pregnancy in the GnRHa group and 20 (5.5%) in the control group (incidence rate ratio, 1.83; 95% CI, 1.06 to 3.15; P = .030). No significant differences in disease-free survival (adjusted hazard ratio, 1.01; 95% CI, 0.72 to 1.42; P = .999) and overall survival (adjusted hazard ratio, 0.67; 95% CI, 0.42 to 1.06; P = .083) were observed between groups. Conclusion Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer

Palliative radiotherapy in addition to self-expanding metal stent for improving dysphagia and survival in advanced oesophageal cancer (ROCS: Radiotherapy after Oesophageal Cancer Stenting):study protocol for a randomized controlled trial

Background: The single most distressing symptom for patients with advanced esophageal cancer is dysphagia. Amongst the more effective treatments for relief of dysphagia is insertion of a self-expanding metal stent (SEMS). It is possible that the addition of a palliative dose of external beam radiotherapy may prolong the relief of dysphagia and provide additional survival benefit. The ROCS trial will assess the effect of adding palliative radiotherapy after esophageal stent insertion. Methods/Design: The study is a randomized multicenter phase III trial, with an internal pilot phase, comparing stent alone versus stent plus palliative radiotherapy in patients with incurable esophageal cancer. Eligible participants are those with advanced esophageal cancer who are in need of stent insertion for primary management of dysphagia. Radiotherapy will be administered as 20 Gray (Gy) in five fractions over one week or 30 Gy in 10 fractions over two weeks, within four weeks of stent insertion. The internal pilot will assess rates and methods of recruitment; pre-agreed criteria will determine progression to the main trial. In total, 496 patients will be randomized in a 1:1 ratio with follow up until death. The primary outcome is time to progression of patient-reported dysphagia. Secondary outcomes include survival, toxicity, health resource utilization, and quality of life. An embedded qualitative study will explore the feasibility of patient recruitment by examining patients’ motivations for involvement and their experiences of consent and recruitment, including reasons for not consenting. It will also explore patients’ experiences of each trial arm. Discussion: The ROCS study will be a challenging trial studying palliation in patients with a poor prognosis. The internal pilot design will optimize methods for recruitment and data collection to ensure that the main trial is completed on time. As a pragmatic trial, study strengths include collection of all follow-up data in the usual place of care, and a focus on patient-reported, rather than disease-orientated, outcomes. Exploration of patient experience and health economic analyses will be integral to the assessment of benefit for patients and the NHS

Randomised, open-label, phase II study of Gemcitabine with and without IMM-101 for advanced pancreatic cancer

Background: Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma. Methods: Patients were randomised (2 : 1) to IMM-101 (10 mg ml−l intradermally)+GEM (1000 mg m−2 intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected. Results: IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44–1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33–0.87, P=0.01). Conclusions: IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study

Cadherin-Dependent Cell Morphology in an Epithelium: Constructing a Quantitative Dynamical Model

Cells in the Drosophila retina have well-defined morphologies that are attained during tissue morphogenesis. We present a computer simulation of the epithelial tissue in which the global interfacial energy between cells is minimized. Experimental data for both normal cells and mutant cells either lacking or misexpressing the adhesion protein N-cadherin can be explained by a simple model incorporating salient features of morphogenesis that include the timing of N-cadherin expression in cells and its temporal relationship to the remodeling of cell-cell contacts. The simulations reproduce the geometries of wild-type and mutant cells, distinguish features of cadherin dynamics, and emphasize the importance of adhesion protein biogenesis and its timing with respect to cell remodeling. The simulations also indicate that N-cadherin protein is recycled from inactive interfaces to active interfaces, thereby modulating adhesion strengths between cells