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

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

Repeating adrenal vein sampling when neither aldosterone/cortisol ratio exceeds peripheral yields a high incidence of aldosterone-producing adenoma

Objectives:In primary aldosteronism, adrenal vein sampling (AVS) suggests unilateral aldosterone-producing adenoma (APA) when the aldosterone/cortisol (A/F) ratio is less than or equal to peripheral on one side and at least two times peripheral on the other. When A/F ratios are lower bilaterally than peripheral despite adequate samples (adrenal venous cortisol 3 times peripheral), we recommend repeat AVS. This study aimed to determine the frequency of this occurrence and outcomes in such cases.Methods:We performed a retrospective observational study of all cases of primary aldosteronism undergoing initial AVS over a 34-year period.Results:Initial AVS in 1397 patients returned satisfactory and discriminatory results in 1066 (76.3%) but 37 patients (2.6%) had adequate samples but bilateral A/F ratios no higher than peripheral. Of the 22 of these 37 who agreed to repeat AVS, 10 demonstrated unilateral aldosterone production, and eight of these had unilateral adrenalectomy disclosing APAs and resulting in cure (3) or improvement (5) in hypertension. Eight had bilateral aldosterone production. Four studies were inconclusive. Patients with initial unsatisfactory AVS because of bilaterally low A/F ratios had significantly (P=0.023) more unilateral disease [10 of 18 satisfactory repeat studies (55.6%) vs. 326 of 1066 satisfactory initial studies (30.6%)] and a significantly higher (67.6 vs. 49.9%, P=0.034) percentage of males.Conclusion:As the incidence of APAs was high in a subgroup with low A/F bilaterally on initial AVS, these patients should be offered repeat AVS. This might reflect both a greater dependence of aldosterone production on adrenocorticotrophic hormone (ACTH) in APAs and the pulsatile nature of ACTH secretion

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

Safety and survival data in patients with idiopathic pulmonary fibrosis treated with nintedanib: Pooled data from six clinical trials

Introduction Nintedanib slows disease progression in patients with idiopathic pulmonary fibrosis (IPF) by reducing the rate of decline in forced vital capacity, with an adverse event profile that is manageable for most patients. We used data from six clinical trials to characterise the safety and tolerability profile of nintedanib and to investigate its effects on survival. Methods Data from patients treated with 651 dose of nintedanib 150 mg two times per day or placebo in the 52-week TOMORROW trial and/or its open-label extension; the two 52-week INPULSIS trials and/or their open-label extension, INPULSIS-ON; and a Phase IIIb trial with a placebo-controlled period of 656 months followed by open-label nintedanib were pooled. All adverse events, irrespective of causality, were included in descriptive analyses. Parametric survival distributions were fit to pooled Kaplan-Meier survival data from the trials and extrapolated to estimate long-term survival. Results There were 1126 patients in the pooled nintedanib group and 565 patients in the pooled placebo group. The mean duration of nintedanib treatment was 28 months. No new safety signals were observed. Incidence rates of bleeding, liver enzyme elevations and cardiovascular events were consistent with those observed in the INPULSIS trials. Diarrhoea was reported at a lower event rate in the pooled nintedanib group than in nintedanib-treated patients in the INPULSIS trials (76.5 vs 112.6 events per 100 patient exposure-years) and infrequently led to permanent treatment discontinuation (3.6 events per 100 patient exposure-years). Based on the Weibull distribution, mean (95% CI) survival was estimated as 11.6 (9.6, 14.1) years in nintedanib-treated patients and 3.7 (2.5, 5.4) years in placebo-treated patients. Conclusions Based on pooled data from six clinical trials, the adverse event profile of nintedanib was manageable for most patients. Exploratory analyses based on extrapolation of survival data suggest that nintedanib extends life expectancy in patients with IPF

High resolution measurements of carbon monoxide along a late Holocene Greenland ice core: evidence for in situ production

We present high-resolution measurements of carbon monoxide (CO) concentrations from a shallow ice core of the North Greenland Eemian Ice Drilling project (NEEM-2011-S1). An optical-feedback cavity-enhanced absorption spectrometer (OF-CEAS) coupled to a continuous melter system performed continuous, online analysis during a four-week measurement campaign. This analytical setup generated stable measurements of CO concentrations with an external precision of 7.8 ppbv (1σ), based on repeated analyses of equivalent ice core sections. However, this first application of this measurement technique suffered from a poorly constrained procedural blank of 48 ± 25 ppbv and poor accuracy because an absolute calibration was not possible. The NEEM-2011-S1 CO record spans 1800 yr and the long-term trends within the most recent section of this record (i.e., post 1700 AD) resemble the existing discrete CO measurements from the Eurocore ice core. However, the CO concentration is highly variable (75–1327 ppbv range) throughout the ice core with high frequency (annual scale), high amplitude spikes characterizing the record. These CO signals are too abrupt and rapid to reflect atmospheric variability and their prevalence largely prevents interpretation of the record in terms of atmospheric CO variation. The abrupt CO spikes are likely the result of in situ production occurring within the ice itself, although the unlikely possibility of CO production driven by non-photolytic, fast kinetic processes within the continuous melter system cannot be excluded. We observe that 68% of the CO spikes are observed in ice layers enriched with pyrogenic aerosols. Such aerosols, originating from boreal biomass burning emissions, contain organic compounds, which may be oxidized or photodissociated to produce CO within the ice. However, the NEEM-2011-S1 record displays an increase of ~0.05 ppbv yr⁻¹ in baseline CO level prior to 1700 AD (129 m depth) and the concentration remains elevated, even for ice layers depleted in dissolved organic carbon (DOC). Thus, the processes driving the likely in situ production of CO within the NEEM ice may involve multiple, complex chemical pathways not all related to past fire history and require further investigation

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

Aims: Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition. Methods: Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken. Results: One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m−2. Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide. Conclusions: Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

Aims: Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition. Methods: Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken. Results: One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m−2. Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide. Conclusions: Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required

The abundance of 44Ti in core collapse supernovae : Measuring the 44Ti(α, p)47V reaction

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