Possibilities of preparation of exotic radionuclide samples at PSI for scientific investigations

The interactions of high-energy protons with matter produce a large variety of radionuclides due to the diversity of the induced nuclear reactions. Some of those isotopes are very rare, exotic, and, in many cases, difficult to produce by complementary methods. Valuable isotopes, interesting for scientific and technological applications, can be extracted from samples stemming from the surroundings or components of a proton accelerator, in particular if the load of the initial particle current is relatively high (esp. in the Megawatt range). Since PSI operates one of the most powerful high-energy proton accelerators world-wide, this facility is best-suited for an R&D program aimed at "harvesting” such isotopes. An initiative called ERAWAST (Exotic Radionuclides from Accelerator Waste for Science and Technology) was started in 2006 in order to identify and motivate potential users. After six years, first achievements as well as realistic future plans for front-end experiments are available. The present contribution describes radiochemical separation techniques for selected examples, summarizes the most prominent results and gives an outlook on the upcoming experiments within the scope of the ERAWAST progra

Ontogenetic changes in the diet of L. forbesi: insights from fatty acid and stable isotope analysis

The diet of L. forbesi in Scottish waters was subject to ontogenetic changes as shown by fatty acid and stable isotope analysis. Crustaceans were more frequently found in stomachs of immature squid smaller than 150 mm mantle length. With increasing size ( > 150 mm) and maturity fish becamemore prominent in the diet. Seasonal differences in the diet were also found but seemed to be linked to seasonal changes in squid size. Prey type and species composition also varied slightly between different regions. Differences between size and region were reflected in fatty acid profiles of mainly the digestive gland tissue. High levels of the saturated fatty acid 16:0 and the polyunsaturated fatty acids 20:5n-3 and 22:6n-3, which are typical for fatty acid signatures of many crustacean species, were found in tissues of smaller immature squid. Higher levels of the monounsaturated fatty acids 16:1n-7, 20:1* and polyunsaturated fatty acids of the linoleic family (C18), which are typical forfish prey species, were found in squid of larger sizes and higher maturity stages. Regional differences found for fatty acid profiles of the digestive gland suggested a significant difference in origin of fatty acids thus indicating different diets. In comparing the fatty acid profiles of squid to those of putative prey species of L. forbesi, it was apparent that gadid species Trisopterus minutus, Micromesistius poutassou and Gadus morhua, were an important component of the diet ofL. forbesi. With increasing size of the predator however the composition of fish species in the diet shifted more towardsGadiculus argenteus, Trachurus trachurus and Sebastes marinus. Results of quantitative fatty acid analysis on the estimate of the contribution of each prey species to the diet also reflected this shift in the importance of different prey species with increasing predator size. Due to slower turnover rates in muscle, changes in carbon and nitrogen stable isotope ratios with diet were more pronounced in this tissue. Smaller squid showed the lowest δ15N ratios thus feeding on the lowest trophic level of all squid examined. δ 13C ratios were the most depleted for small squid indicating that small squid feed on prey closer to the carbon source in the food chain. Stable isotope analysis also showed that squid with fish remains in their stomachs showed higher ratios of nitrogen and less depleted carbon ratios than squid feeding on crustaceans. Comparisons of isotope levels of squid and putative prey species identified blue whiting and silvery pout as putative prey species of bigger sized squid. Small squid seemed to feed on the same trophic level and all other prey species examined were always similar or higher in isotope ratios than squid of any size

Radiochemical separation of 7Be from the cooling water of the neutron spallation source SINQ at PSI

7Be is a key radionuclide for investigation of several astrophysical processes and phenomena. In addition, it is used as a tracer in wear measurements. It is produced in considerable amounts in the cooling water (D2O) of the Spallation Induced Neutron Source (SINQ) facility at PSI by spallation reactions on 16O with the generated fast neutrons. A shielded ion-exchange filter containing 100 mL of the mixed-bed ion exchanger LEWATIT was installed as a bypass for the cooling water into the cooling loop of SINQ for three months. The collected activity of 7Be was in the range of several hundred GBq. Further, the 7Be was separated and purified in a hot-cell remotely-controlled using a separation system installed. With the exception of 10Be, radioactive byproducts can be neglected, so that this cooling water could serve as an ideal source for highly active 7Be-samples. The facility is capable of producing 7Be with activities up to 1 TBq per year. The 7Be sample preparation is described in detail and the possible uses are discussed. In particular some preliminary results of 7Be ion beam production are presente

Current status of using beaks to identify cephalopods: III International Workshop and training course on Cephalopod beaks, Faial island, Azores, April 2007

The identification of cephalopods using their beaks is still a difficult technique. To increase our knowledge of this technique and stimulate a new generation of beak experts, the III International beak workshop and training course was organized in Faial, Azores Islands in 2007. We briefly review the activities of the workshop, including the identification procedure of lower beaks of cephalopods from predators with emphasis on cetaceans, seals, fish and seabirds; provision of basic knowledge to young researchers interested in the study area; identification of recent developments in beak research; and discussion of the main problematic issues. The families that need particular attention are Brachioteuthidae, Chiroteuthidae, Cranchiidae, Cycloteuthidae, Mastigoteuthidae, Octopoteuthidae, Promachoteuthidae, Onychoteuthidae (particularly the genus Walvisteuthis), Mastigoteuthidae and Cirroteuthidae. The stable isotopic signature of beaks is capable of revealing new trophic relationships and migrations. Future work should focus on: a) obtaining more cephalopod material from research cruises; b) promoting a close and continuous collaboration between beak experts and cephalopod taxonomists and; c) developing new, and updated, beak guides

Meta-analysis of effect of nintedanib on reducing FVC decline across interstitial lung diseases

INTRODUCTION: The effect of nintedanib on slowing the rate of decline in forced vital capacity (FVC) has been investigated in randomized placebo-controlled trials in subjects with idiopathic pulmonary fibrosis (IPF), other progressive fibrosing interstitial lung diseases (ILDs), and ILD associated with systemic sclerosis (SSc-ILD). We assessed the consistency of the effect of nintedanib on the rate of decline in FVC over 52 weeks across four placebo-controlled phase III trials. METHODS: We used data on FVC decline from the INPULSIS-1 and INPULSIS-2 trials in subjects with IPF, the INBUILD trial in subjects with progressing fibrosing ILDs other than IPF, and the SENSCIS trial in subjects with SSc-ILD. In each trial, the primary endpoint was the annual rate of decline in FVC (mL/year) assessed over 52 weeks. We performed fixed effect and random effects meta-analyses based on the relative treatment effect of nintedanib versus placebo on the rate of decline in FVC (mL/year) over 52 weeks. Heterogeneity of the relative treatment effect of nintedanib across populations was assessed using the I2 statistic, τ2 and corresponding p value from a Q test for heterogeneity. RESULTS: The combined analysis comprised 1257 subjects treated with nintedanib and 1042 subjects who received placebo. Nintedanib reduced the rate of decline in FVC (mL/year) over 52 weeks by 51.0% (95% CI 39.1, 63.0) compared with placebo. The relative effect (95% CI) was the same using the fixed effect and random effects models. There was no evidence of heterogeneity in the relative treatment effect of nintedanib across the populations studied (I2 = 0%, τ2 = 0, p = 0.93). CONCLUSIONS: A meta-analysis of data from four placebo-controlled trials demonstrated that nintedanib approximately halved the rate of decline in FVC over 52 weeks across subjects with different forms of pulmonary fibrosis, with no evidence of heterogeneity in its relative treatment effect across patient populations

Characterisation of exacerbation risk and exacerbator phenotypes in the POET-COPD trial

Background: Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce. Methods: Post-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint. Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or >= 2 exacerbations during study treatment), irrespective of study treatment. A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation. Results: In total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators. Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses. Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and >= 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers. The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality. Conclusion: The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer surviva

The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline.

Abstract Objective: To develop clinical practice guidelines for the management of patients with primary aldosteronism. Participants: The Task Force included a chair, selected by the Clinical Guidelines Subcommittee of the Endocrine Society, six additional experts, a methodologist, and a medical writer. The guideline was cosponsored by American Heart Association, American Association of Endocrine Surgeons, European Society of Endocrinology, European Society of Hypertension, International Association of Endocrine Surgeons, International Society of Endocrinology, International Society of Hypertension, Japan Endocrine Society, and The Japanese Society of Hypertension. The Task Force received no corporate funding or remuneration. Evidence: We searched for systematic reviews and primary studies to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation group criteria to describe both the quality of evidence and the strength of recommendations. We used "recommend" for strong recommendations and "suggest" for weak recommendations. Consensus Process: We achieved consensus by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. With the help of a medical writer, the Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and Council successfully reviewed the drafts prepared by the Task Force. We placed the version approved by the Clinical Guidelines Subcommittee and Clinical Affairs Core Committee on the Endocrine Society's website for comments by members. At each stage of review, the Task Force received written comments and incorporated necessary changes. Conclusions: For high-risk groups of hypertensive patients and those with hypokalemia, we recommend case detection of primary aldosteronism by determining the aldosterone-renin ratio under standard conditions and recommend that a commonly used confirmatory test should confirm/exclude the condition. We recommend that all patients with primary aldosteronism undergo adrenal computed tomography as the initial study in subtype testing and to exclude adrenocortical carcinoma. We recommend that an experienced radiologist should establish/exclude unilateral primary aldosteronism using bilateral adrenal venous sampling, and if confirmed, this should optimally be treated by laparoscopic adrenalectomy. We recommend that patients with bilateral adrenal hyperplasia or those unsuitable for surgery should be treated primarily with a mineralocorticoid receptor antagonist

Effects of nintedanib in patients with idiopathic pulmonary fibrosis by GAP stage

We conducted a post hoc analysis to assess the potential impact of GAP (gender, age, physiology) stage on the treatment effect of nintedanib in patients with idiopathic pulmonary fibrosis. Outcomes were compared in patients at GAP stage I versus II/III at baseline in the INPULSIS\uae trials. At baseline, 500 patients were at GAP stage I (nintedanib 304, placebo 196), 489 were at GAP stage II (nintedanib 296, placebo 193) and 71 were at GAP stage III (nintedanib 38, placebo 33). In nintedanibtreated patients, the annual rate of decline in forced vital capacity (FVC) was similar in patients at GAP stage I and GAP stage II/III at baseline (-110.1 and -116.6 mL.year-1, respectively), and in both subgroups was lower than in placebo-treated patients (-218.5 and -227.6 mL.year-1, respectively) (treatment-by-time-by-subgroup interaction p=0.92). In the nintedanib group, the number of deaths was 43.8% of those predicted based on GAP stage (35 versus 79.9). In the placebo group, the number of deaths was 59.8% of those predicted based on GAP stage (33 versus 55.2). In conclusion, data from the INPULSIS\uae trials suggest that nintedanib has a similar beneficial effect on the rate of FVC decline in patients at GAP stage I versus II/III at baseline

Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS® trials

AbstractBackground and purposeThe Phase II TOMORROW trial and two Phase III INPULSIS® trials investigated the efficacy and safety of nintedanib versus placebo in patients with idiopathic pulmonary fibrosis (IPF). To obtain an overall estimate of the treatment effect of nintedanib 150 mg twice daily (bid), pooled and meta-analyses of data from these three trials were conducted.MethodsPooled and meta-analyses were conducted for annual rate of decline in forced vital capacity (FVC), time to first acute exacerbation, change from baseline in St George's Respiratory Questionnaire (SGRQ) total score and mortality over 52 weeks.Results1231 patients (nintedanib n = 723, placebo n = 508) were included in the pooled analysis. Adjusted annual rate of decline in FVC was −112.4 mL/year with nintedanib and −223.3 mL/year with placebo (difference: 110.9 mL/year [95% CI: 78.5, 143.3]; p < 0.0001). The hazard ratio for time to first acute exacerbation was 0.53 (95% CI: 0.34, 0.83; p = 0.0047). Adjusted mean change from baseline in SGRQ score at week 52 was 2.92 with nintedanib and 4.97 with placebo (difference: −2.05 [95% CI: −3.59, −0.50]; p = 0.0095). Hazard ratios for time to all-cause and on-treatment mortality were 0.70 (95% CI: 0.46, 1.08; p = 0.0954) and 0.57 (95% CI: 0.34, 0.97; p = 0.0274), respectively, in favour of nintedanib. The meta-analysis was generally consistent with the pooled analysis. Diarrhoea was the most frequent adverse event in the nintedanib group (61.5% of patients treated with nintedanib versus 17.9% of patients treated with placebo).ConclusionNintedanib has a beneficial effect on slowing disease progression in patients with IPF