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Problem definition: To approve a novel drug therapy, the U.S. Food and Drug Administration (FDA) requires clinical trial evidence demonstrating efficacy with 2.5% statistical significance, although the agency often uses regulatory discretion when interpreting these standards. Factors including disease severity, prevalence, and availability of existing therapies are qualitatively considered; yet, current guidelines fail to systematically consider such characteristics in approval decisions. Academic/practical relevance: In making approval decisions, the FDA weighs the health benefits of introducing life-saving therapies against the potential risks of approving ineffective or harmful drugs. Tailoring approval standards to individual diseases could improve treatment options for patients with few alternatives and further incentivize pharmaceutical companies to invest in neglected diseases. Methodology: Using a novel queueing framework, we analyze the FDA’s drug approval process to incorporate disease-specific factors and obsolescence—newer drugs replacing older formulas—through a set of pre-emptive M/M/1/1 queues. Based on public data encompassing all registered U.S. clinical trials and FDA-approved drugs, we estimate model parameters for three high-burden diseases (breast cancer, human immunodeficiency virus (HIV), and hypertension) and solve for the optimal policy to maximize net life-years gained following FDA approval. Results: The optimal policy relaxes approval standards for diseases with long trial duration, high attrition, or low research and development intensity. Results indicate that a more lenient policy is warranted for drugs targeting breast cancer or hypertension, and a more stringent policy is recommended for HIV, relative to the FDA’s existing policy. If pharmaceutical firms respond to the new standards by submitting more drugs for approval—leading to an endogenous clinical trial initiation rate—the FDA’s optimal policy modestly decreases for breast cancer and hypertension, with minimal change for HIV. Managerial implications: Our study offers a transparent, quantitative framework that could help the FDA develop disease-specific approval guidelines based on underlying disease-related severity, prevalence, and characteristics of the drug development process and existing market.

Once considered to be exotic species of limited synthetic utility, vinyl cations have recently been shown to be highly versatile intermediates in a variety of processes. Here, we report a method for the synthesis of aryl-substituted benzocycloheptenes and -hexenes using the hydrotriflate salt of an electron-poor pyridine as a uniquely efficient proton source for a vinyl cation mediated Friedel-Crafts cyclization. The mild conditions made possible by this reagent allowed a range of simple and functionalized alkynes bearing pendant aryl groups to serve as suitable substrates for this scalable and convenient protocol.

Purpose Academics are more likely to suffer from mental health disorders such as depression and anxiety yet are less likely to seek treatment. Stigma is one of the highest ranked barriers to help-seeking for mental health problems. Strikingly, however, there is limited data on interventions to improve mental health outcomes in academia by decreasing mental health-related stigma despite the prevalence and impact of mental health issues on academic performance and lifestyle. Design Here we report a study conducted by Dragonfly Mental Health (DMH) at the University of California Berkeley in the Molecular and Cell Biology Department to assess the effectiveness of first-person narratives in decreasing mental health stigma. For this study, personal stories of 6 local faculty with lived experience of mental health struggles were shown in a short film during three separate divisional retreats. The audience members were then anonymously surveyed after the screening. Results The screening of the film was deemed beneficial by an overwhelming majority of participants, both with respect to reducing stigma and by fostering conversations about mental health culture. Implications This data suggests that sharing faculty stories is a powerful mechanism to reduce stigma, promote more open communication, and foster change in academic culture around mental health issues., This document is part of the Book of Abstracts of the ReMO 2022 Conference that was organized within the framework of COST Action CA19117 - "Researcher Mental Health".

Cyclopentadienyliron dicarbonyl based allenyliron complexes were prepared, and their formal [3 + 2] cycloaddition with a number of dipolar reagents was investigated as a means of preparing heterocy...

Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain.The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery.Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years.Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04).After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).

The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days.Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life.By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01).Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

For irradiation experiments (e.g., of per- and polyfluoroalkyl substances), values of nuclear particle flux and absorbed dose rates were obtained for the Safe LOW-POwer Kritical Experiment-2 (SLOWP...

In this work, a thermodynamic treatment for (Th,U)O2 and (Th,Pu)O2 fuels has been developed using the CALPHAD method to describe phase diagram and thermodynamic data of the phases in the Th-U-Pu-O sub-systems. The treatment builds on previously reported assessments of the U-Pu-O ternary oxide system and of the Th-U-Pu ternary metallic system. The thermodynamic and phase diagram properties calculated by the models herein are in good agreement with available experimental data for the binary and ternary subsystems, as well as new phase diagram data for the Th-O binary reported here. This treatment is useful to predict thermodynamic behavior of thoria-based nuclear fuels at various temperatures and compositions.

New Experiments with Spheres-Gas (NEWS-G) is a dark matter direct detection experiment that will operate at SNOLAB (Canada). Similar to other rare-event searches, the materials used in the detector construction are subject to stringent radiopurity requirements. The detector features a 140-cm diameter proportional counter comprising two hemispheres made from commercially sourced 99.99% pure copper. Such copper is widely used in rare-event searches because it is readily available, there are no long-lived Cu radioisotopes, and levels of non-Cu radiocontaminants are generally low. However, measurements performed with a dedicated 210Po alpha counting method using an XIA detector confirmed a problematic concentration of 210Pb in bulk of the copper. To shield the proportional counter's active volume, a low-background electroforming method was adapted to the hemispherical shape to grow a 500-$��$m thick layer of ultra-radiopure copper to the detector's inner surface. In this paper the process is described, which was prototyped at Pacific Northwest National Laboratory (PNNL), USA, and then conducted at full scale in the Laboratoire Souterrain de Modane in France. The radiopurity of the electroplated copper was assessed through Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Measurements of samples from the first (second) hemisphere give 68% confidence upper limits of, 11 pages, 11 figures, 3 tables

Heterotopic cardiac transplantation in the intra-abdominal position in a large animal model has been essential in the progression of the field of cardiac transplantation. Our group has over 10 years of experience in cardiac xenotransplantation with pig to baboon models, the longest xenograft of which survived over 900 days, with rejection only after reducing immunosuppression. This article aims to clarify our approach to this model in order to allow others to share success in long-term survival. Here, we demonstrate the approach to implantation of a cardiac graft into the intra-abdominal position in a baboon recipient for the study of transplantation and briefly highlight our model’s ability to provide insight into not only xenotransplantation but across disciplines. We include details that have provided us with consistent success in this model; performance of the anastomoses, de-airing of the graft, implantation of a long-term telemetry device for invasive graft monitoring, and ideal geometric positioning of the heart and telemetry device in the limited space of the recipient abdomen. We additionally detail surveillance techniques to assess long-term graft function.

The Thermodynamics of Advanced Fuels – International Database (TAF-ID) was developed using the Calphad method to provide a computational tool to perform thermodynamic calculations on nuclear fuel materials under normal and off-normal conditions. Different kinds of fuels are considered: oxide, metallic, carbide and nitride fuels. Many fission products are introduced as well as structural materials (e.g., zirconium, steel, concrete, SiC) and absorbers (e.g., B4C), in order to investigate the thermochemistry of irradiated fuels and to predict their chemical interaction with the surrounding materials. The approach to develop the database and the models implemented in the database are described. Examples of models for key chemical systems are presented. Finally, a few examples of application calculations on severe accidents with UO2 fuels, irradiated fuel chemistry of MOX and metallic fuels and metallic fuel/cladding interaction show how this tool can be used. To validate the database, the calculations are compared to the available experimental data. A good agreement is obtained which gives confidence in the maturity degree and quality of the TAF-ID database. The working version is only accessible to the participants of the TAF-ID project (Canada, France, Japan, the Netherlands, Republic of Korea, United Kingdom, USA). A public version is accessible by all the NEA countries. The current version contains models on the Am–Fe, Am–Np, Am-O-Pu, Am–U, Am–Zr, C–O–U-Pu, Cr–U, Np–U, Np–Zr, O–U–Zr, Re–U, Ru–U, Si–U, Ti–U, U-Pu-Zr, U–W systems. It is progressively extended with our published assessments. Information on how to join the project is available on the website: https://www.oecd-nea.org/science/taf-id/.

Correction for ‘Microfluidic ELISA employing an enzyme substrate and product species with similar detection properties’ by Basant Giri et al., Analyst, 2018, 143, 989–998, https://doi.org/10.1039/C7AN01671A.

In recent years, atom probe tomography (APT) has been increasingly used to study minerals, and in particular the mineral zircon. Zircon (ZrSiO4) is ideally suited for geochronology by utilising the U-Th-Pb isotope systems, and trace element compositions are also widely used to constrain petrogenetic processes. However, while standard geoanalytical techniques provide information at micrometer scale lengths, the unique combination of chemical/isotopic sensitivity and spatial resolution of APT allows compositional and textural measurements at the nanoscale. This interlaboratory study aims to define the reproducibility of APT data across research facilities and assess the role of different aspects of the atom probe workflow on reproducibility. This is essential to allow correct evaluation of APT results and full utilization of this emerging technique within the geoscience community. In this study, nine samples from the same homogeneous, GJ-1/87 zircon reference grain were sent to nine APT institutes in Germany, the UK, USA, Canada and Australia. After preparing the sample out of a selectioned slab, each institute conducted three different rounds of APT analyses: using (i) unconstrained analysis parameters, (ii) pre-defined analysis parameters, and (iii) interpreting and quantifying a provided dataset. Data such as the measured elemental composition, acquisition parameters, or mass spectrum peak identifications, were recorded and analyzed. We observe a significant variation in the measured composition across this interlaboratory study as well as the number of trace elements identified. These differences are thought to directly result from the user's choice of atom probe data analysis parameters. The type of instrument does not seem to be a critical factor. Consequently, comparison of absolute trace element concentrations on zircon using APT between laboratories is only valid if the same workflow has been ensured.

Ar-37 has been prepared from micron- and nano- diameter CaO by irradiation in the predominantly thermal flux of a SLOWPOKE-2 reactor. A polyether ether ketone irradiation vial facilitates irradiation in vacuo to yield radio-argon as the sole gaseous product. Gamma-emitting Ar-41(T1/2 = 110 min) is used to infer Ar-37 activity, although 40Ar(n, γ)41Ar also occurs as a result of air entrapped within the CaO matrix. Less air is present in the nano-CaO matrix and more radio-argon is liberated to the gas phase. Using nano-CaO, 96 ± 10% of predicted Ar-41 is observed following Ar-41 diffusion to an un-irradiated container.

New Experiments With Spheres-Gas (NEWS-G) is a direct dark matter detection experiment using Spherical Proportional Counters (SPCs) with light noble gases to search for low-mass Weakly Interacting Massive Particles (WIMPs). We report the results from the first physics run taken at the Laboratoire Souterrain de Modane (LSM) with SEDINE, a 60 cm diameter prototype SPC operated with a mixture of $\mathrm{Ne}+\mathrm{CH}_{4}$ (0.7 %) at 3.1 bars for a total exposure of $9.7\;\mathrm{kg\cdot days}$. New constraints are set on the spin-independent WIMP-nucleon scattering cross-section in the sub-$\mathrm{GeV/c^2}$ mass region. We exclude cross-sections above $4.4 \times \mathrm{10^{-37}\;cm^2}$ at 90 % confidence level (C.L.) for a 0.5 $\mathrm{GeV/c^2}$ WIMP. The competitive results obtained with SEDINE are promising for the next phase of the NEWS-G experiment: a 140 cm diameter SPC to be installed at SNOLAB by summer 2018., Comment: 18 pages, 10 figures, acknowledgments section updated

The requirement for the enzyme label to carry out a chemical reaction directly at the signaling region of the enzyme substrate in order to produce a large change in its detectability places a significant constraint on the scope of enzyme-linked immunosorbent assays (ELISAs). In particular, this requirement limits the kinds of enzyme label-substrate couples employable in ELISAs and prevents their independent optimization with respect to the enzyme reaction and the detectability of the enzyme reaction substrate/product. The detection limit and multiplexing capabilities of the assay are consequently restricted in addition to rendering the technique applicable to a narrow range of assay conditions/samples. Attempting to address some of these limitations, the current article describes a microfluidic ELISA method that does not require the enzyme label to act around the signaling region of the substrate molecule. A highly detectable rhodamine based substrate was synthesized to demonstrate the reported assay which upon cleavage by the enzyme label, alkaline phosphatase, transformed from a monoanionic to a monocationic species both of which had nearly identical fluorescence properties. These species were later separated based on their charge difference using capillary zone electrophoresis in an integrated device yielding a quantitative measure for the analyte (human TNF-α) in our sample. Impressively, the noted approach not only enabled the use of a new kind of enzyme substrate for ELISAs but also allowed the detection of human TNF-α at concentrations over 54-fold smaller than that possible on commercial microwell plates primarily due to the better detectability of the rhodamine dye.

To determine the frequency and risk factors for non-home discharge (NHD) and its association with clinical outcomes and quality of life (QOL) at 1 year following cardiac surgery in patients with ischemic mitral regurgitation (IMR).Discharge disposition was evaluated in 552 patients enrolled in trials of severe or moderate IMR. Patient and in-hospital factors associated with NHD were identified using logistic regression. Subsequently, association of NHD with 1-year mortality, serious adverse events (SAEs), and QOL was assessed.NHD was observed in 30% (154/522) with 25% (n = 71/289) in moderate and 36% (n = 83/233) in patients with severe IMR (unadjusted P = .006), a difference not significant after including age (5-year change: adjusted odds ratio [adjOR], 1.52; 95% confidence interval [CI], 1.35-1.72; P .001), diabetes (adjOR, 1.94; 95% CI, 1.27-2.94; P = .002), and previous heart failure (adjOR, 1.64; 95% CI, 1.06-2.52; P = .03). Odds of NHD were increased for patients with postoperative SAEs (adjOR, 1.85; 95% CI, 1.19-2.86; P = .01) but not based on type of cardiac surgery. Greater rates of death and SAEs were observed in NHD patients at 1 year: adjusted hazard ratio, 4.29 (95% CI, 2.14-8.59; P .001) and adjusted rate ratio, 1.45 (95% CI, 1.03-2.02; P = .03), respectively. QOL did not differ significantly between groups.NHD is common following surgery for IMR, influenced by older age, diabetes, previous heart failure, and postoperative SAEs. These patients may be at greater risk of death and subsequent SAEs after discharge. Discussion of NHD with patients may have important implications for decision-making and guiding expectations following cardiac surgery.

Fuel-Cladding Chemical Interaction (FCCI) in metallic nuclear fuels is a key phenomenon that limits the maximum burn-up and operating power as it can cause premature failure of the fuel cladding. Therefore, being able to accurately predict the interactions of the fuel-cladding system by means of thermodynamic calculations contributes to our understanding of how to mitigate this failure mechanism. In order to test the capabilities of the Thermodynamic of Advanced Fuels – International Database (TAF-ID) to predict these interactions, calculations have been performed on two irradiated metallic fuels: U-5Fs in SS316 cladding and U-10Zr in HT9 cladding, for which experimental observations are available in the literature. TAF-ID calculations have allowed the confirmation of some of the phases that were observed during experimental characterizations and the identification of unknown ones: Particularly for the U-5Fs fuel, two primary Fe-rich phases have been predicted: (i) FeU6, that extends up to 120 μm into the fuel, and (ii) UFe2 with >30 wt.% Fe, likely to be the Fe-rich layer observed experimentally adjacent to the cladding on the fuel side. Also, minor phases that have been experimentally observed, such as U-Mo, U-Ru, and lanthanoid-noble metals (Nd,Ce-Pd), have been predicted to be stable. As for the U-10Zr fuel, calculations predicted several U-Fe-Zr phases (e.g., FeU6, UFe2, and χ-FeUZr), Fe-(Ce,Nd) phases (e.g., Fe17Ln2), and a FCC phase consisting of Ce, Nd, La, Y, and Sr. These predicted phases are in excellent agreement with experimental observations.

In the chemometric context in which spectral loadings of the analytes are already known, spectral filter functions may be constructed which allow the scores of mixtures of analytes to be determined in on-the-fly fashion directly, by applying a compressive detection strategy. Rather than collecting the entire spectrum over the relevant region for the mixture, a filter function may be applied within the spectrometer itself so that only the scores are recorded. Consequently, compressive detection shrinks data sets tremendously. The Walsh functions, the binary basis used in Walsh–Hadamard transform spectroscopy, form a complete orthonormal set well suited to compressive detection. A method for constructing filter functions using binary fourfold linear combinations of Walsh functions is detailed using mathematics borrowed from genetic algorithm work, as a means of optimizing said functions for a specific set of analytes. These filter functions can be constructed to automatically strip the baseline from analysis. Monte Carlo simulations were performed with a mixture of four highly overlapped Raman loadings and with ten excitation–emission matrix loadings; both sets showed a very high degree of spectral overlap. Reasonable estimates of the true scores were obtained in both simulations using noisy data sets, proving the linearity of the method.

The thermodynamically equilibrium precipitates that form in the Zr-Excel alloy after long-term (2500 h) annealing at 550 °C were investigated with transmission electron microscopy and X-ray diffraction techniques. The equilibrium precipitates were found to be a form of cubic Zr(Mo,Nb,Fe) 2 with about 26.5 at.% Mo substituted by Nb. Differential scanning calorimetry (DSC) heating curves show that the phase transformation sequence is αZr + Zr(Mo,Nb,Fe) 2 → αZr + Zr(Mo,Nb,Fe) 2 + βZr → αZr + βZr → βZr upon heating the long-term annealing alloy. With the heating rate of 10 °C/min, the αZr is found to transform into βZr at 530 °C, and Zr(Mo,Nb,Fe) 2 completely dissolves at a temperature higher than 771 °C, while the αZr disappears at 969 °C.

Introduction: This study explored the nature of the association between intraoperative usage of red blood cell, fresh frozen plasma, cryoprecipitate or platelet transfusions and acute kidney injury. Methods: A total of 1175 patients who underwent cardiac surgery between 2008 and 2013 were retrospectively analyzed. We assessed the association between: (1) preoperative patient characteristics and acute kidney injury, (2) intraoperative blood product usage and acute kidney injury, (3) acute kidney injury and 30-day mortality or re-hospitalization. Results: In our cohort of 1175 patients, 288 patients (24.5%) developed acute kidney injury. This included 162 (13.8%), 69 (5.9%) and 57 (4.9%) developing stage 1, stage 2 or stage 3 acute kidney injury, respectively. Increased red blood cell, fresh frozen plasma or platelet transfusions increased the odds of developing acute kidney injury. Specifically, every unit of red blood cells, fresh frozen plasma or platelets transfused was associated with an increase in the covariate-adjusted odds ratio of developing ⩾ stage 2 kidney injury of 1.18, 1.19 and 1.04, respectively. Conclusions: Intraoperative blood product transfusions were independently associated with an increased odds of developing acute kidney injury following cardiac surgery. Further randomized studies are needed to better define intraoperative transfusion criteria.

Thermodynamic models of complex chemical systems provide an elegant and cost effective means to predict chemical interactions of materials and to provide guidance to experimental research to minimise costs. Starting in 1995 at the Royal Military College of Canada, a thermodynamic treatment of irradiated nuclear fuel has been developed that not only describes the thermochemistry of the fuel at elevated temperatures during a potential Loss-of-Coolant Accident (LOCA), but it can also be used to help predict the oxidation environment for fresh fuel measurements, irradiated fuel behaviour, the aqueous chemistry of fuel debris in coolant, nuclear waste disposal, and other systems involving nuclear fuel. Furthermore, this treatment was supported by several experimental campaigns at the Canadian Nuclear Laboratories and the Institute of Transuranium Elements for validation purposes. This paper will trace the development of this treatment and demonstrate its current practice and future potential in the general context of performance and safety of nuclear fuel.

A series of laboratory-scale combustion tests were conducted under well-controlled conditions to measure the release of 90 Sr and 137 Cs nuclides to the atmosphere (air) from combustion of vegetation and organic soil samples contaminated with radioactivity. These vegetation and soil samples were collected from a controlled contaminated forest area within the Canadian Nuclear Laboratories – Chalk River site. The combustion products including ash and smoke particulates, along with gaseous emissions, were collected and then analyzed for 137 Cs and 90 Sr concentrations by radiometric techniques. The experimental results reveal that the releases of 90 Sr to the atmosphere (air) from combustion of vegetation are very low with most of the 90 Sr activity remaining in ash residues, even at a temperature of 800 °C. The detailed combustion experiments with surface litter and twigs, alder twigs, alder leaves, and organic soil indicate that 0.5 ± 0.1%, 0.3 ± 0.1%, 0.9 ± 0.1%, and 0.3 ± 0.1% of 90 Sr is released to the atmosphere (air), respectively. On the other hand, the releases of 137 Cs are found to be highly dependent on the combustion temperature as well as the nature of vegetation. The releases of 137 Cs obtained at 800 °C are 45 ± 7%, 77 ± 9%, 92 ± 5%, and 2.4 ± 0.5% for surface litter and twigs, alder twigs, alder leaves, and organic soil, respectively. The mechanism associated with the high release of 137 Cs at a high temperature of 800 °C was explored.

A delayed neutron counting (DNC) system, where the sample to be analyzed remains stationary in a thermal neutron beam outside of the reactor, has been developed at the National Research Universal (NRU) reactor of the Canadian Nuclear Laboratories (CNL) at Chalk River. The new in-beam DNC is a novel approach for non-destructive characterization of special nuclear materials (SNM) that could enable identification and quantification of fissile isotopes within a large and shielded sample. Despite the orders of magnitude reduction in neutron flux, the in-beam DNC method can be as informative as the conventional in-core DNC for most cases while offering practical advantages and mitigated risk when dealing with large radioactive samples of unknown origin. This paper addresses (1) the qualification of in-beam DNC using a monochromatic thermal neutron beam in conjunction with a proven counting apparatus designed originally for in-core DNC, and (2) application of in-beam DNC to an examination of large sealed capsules containing unknown radioactive materials. Initial results showed that the in-beam DNC setup permits non-destructive analysis of bulky and gamma shielded samples. The method does not lend itself to trace analysis, and at best could only reveal the presence of a few milligrams of 235U via the assay of in-beam DNC total counts. Through analysis of DNC count rates, the technique could be used in combination with other neutron or gamma techniques to quantify isotopes present within samples.

International audience; The chemical behaviour of the main elements present in a PWR irradiated fuel sample (UO$_2$ fuel, Zr from the Zircaloy-cladding, Pu, Np, and fission products such as Ba, Ce, Cs, Gd, I, La, Mo, Nd, Pd, Rh, Ru, Sr, Tc, Te, etc.) submitted to a nuclear severe accident type sequence (VERDON-1 experiment) has been investigated by thermodynamic calculations using the TAF-ID database. Particular emphasis has been placed on the chemical behaviour of the fission products Ba, Cs, Mo, and Zr, and the interactions between the Zircaloy-cladding and the UO$_2$ matrix. Calculation results have been compared to experimental observations completed during the VERDON-1 experiment (instantaneous release of fission products and final chemical state of elements in the sample). Results presented in this manuscript do not account for non-equilibrium phenomena that have a major impact on fission product behaviour (e.g., chemical diffusion, mass transport induced by temperature gradients in the fuel pellet, etc.). None the less, these TAF-ID calculations have described accurately the melting of the sample following the formation of a mixed (U,Zr)O$_2$-x phase because of the interaction between the fuel and the Zircaloy-cladding. Furthermore, calculations have assisted in the explanation of the instantaneous released fractions observed for Ba and Mo during the experiment (as a function of the experiment atmosphere and temperature).

Objective The Cardiothoracic Surgical Trials Network reported that left ventricular reverse remodeling at 2 years did not differ between patients with moderate ischemic mitral regurgitation randomized to coronary artery bypass grafting plus mitral valve repair (n = 150) or coronary artery bypass grafting alone (n = 151). To address health resource use implications, we compared costs and quality-adjusted survival. Methods We used individual patient data from the Cardiothoracic Surgical Trials Network trial on survival, hospitalizations, quality of life, and US hospitalization costs to estimate cumulative costs and quality-adjusted life years. A microsimulation model was developed to extrapolate to 10 years. Bootstrap and deterministic sensitivity analyses were performed to address uncertainty. Results In-hospital costs were $59,745 for coronary artery bypass grafting plus mitral valve repair versus $51,326 for coronary artery bypass grafting alone (difference $8419; 95% uncertainty interval, 2259-18,757). Two-year costs were $81,263 versus $67,341 (difference 13,922 [2370 to 28,888]), and quality-adjusted life years were 1.35 versus 1.30 (difference 0.05; −0.04 to 0.14), resulting in an incremental cost-effectiveness ratio of $308,343/quality-adjusted life year for coronary artery bypass grafting plus mitral valve repair. At 10 years, its costs remained higher ($107,733 vs $88,583, difference 19,150 [−3866 to 56,826]) and quality-adjusted life years showed no difference (−0.92 to 0.87), with 5.08 versus 5.08. The likelihood that coronary artery bypass grafting plus mitral valve repair would be considered cost-effective at 10 years based on a cost-effectiveness threshold of $100K/quality-adjusted life year did not exceed 37%. Only when this procedure reduces the death rate by a relative 5% will the incremental cost-effectiveness ratio fall below $100K/quality-adjusted life year. Conclusions: The addition of mitral valve repair to coronary artery bypass grafting for patients with moderate ischemic mitral regurgitation is unlikely to be cost-effective. Only if late mortality benefits can be demonstrated will it meet commonly used cost-effectiveness criteria.

Heterotopic cardiac xenotransplantation in the intra-abdominal position has been studied extensively in a pig-to-baboon model to define the optimal donor genetics and immunosuppressive regimen to prevent xenograft rejection. Extensive investigation using this model is a necessary stepping stone toward the development of a life-supporting animal model, with the ultimate goal of demonstrating suitability for clinical cardiac xenotransplantation trials. Aspects of surgical technique, pre- and post-operative care, graft monitoring, and minimization of infectious risk have all required refinement and optimization of heterotopic cardiac xenotransplantation over time. This review details non-immunologic obstacles relevant to this model described by our group and in the literature, as well as strategies that have been developed to address these specific challenges.

Background The incidence of permanent pacemaker (PPM) implantation is higher following mitral valve surgery (MVS) with ablation for atrial fibrillation (AF) compared with MVS alone. Objectives This study identified risk factors and outcomes associated with PPM implantation in a randomized trial that evaluated ablation for AF in patients who underwent MVS. Methods A total of 243 patients with AF and without previous PPM placement were randomly assigned to MVS alone (n = 117) or MVS + ablation (n = 126). Patients in the ablation group were further randomized to pulmonary vein isolation (PVI) (n = 62) or the biatrial maze procedure (n = 64). Using competing risk models, this study examined the association among PPM and baseline and operative risk factors, and the effect of PPM on time to discharge, readmissions, and 1-year mortality. Results Thirty-five patients received a PPM within the first year (14.4%), 29 (83%) underwent implantation during the index hospitalization. The frequency of PPM implantation was 7.7% in patients randomized to MVS alone, 16.1% in MVS + PVI, and 25% in MVS + biatrial maze. The indications for PPM were similar among patients who underwent MVS with and without ablation. Ablation, multivalve surgery, and New York Heart Association functional (NYHA) functional class III/IV were independent risk factors for PPM implantation. Length of stay post-surgery was longer in patients who received PPMs, but it was not significant when adjusted for randomization assignment (MVS vs. ablation) and age (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.61 to 1.08; p = 0.14). PPM implantation did not increase 30-day readmission rate (HR: 1.43; 95% CI: 0.50 to 4.05; p = 0.50). The need for PPM was associated with a higher risk of 1-year mortality (HR: 3.21; 95% CI: 1.01 to 10.17; p = 0.05) after adjustment for randomization assignment, age, and NYHA functional class. Conclusions AF ablation, multivalve surgery, and NYHA functional class III/IV were associated with an increased risk for permanent pacing. PPM implantation following MVS was associated with a significant increase in 1-year mortality. (Surgical Ablation Versus No Surgical Ablation for Patients With Atrial Fibrillation Undergoing Mitral Valve Surgery; NCT00903370)

International audience; Spherical proportional counters (SPCs) are a novel gaseous detector technology employed by the NEWS-G low-mass dark matter search experiment for their high sensitivity to single electrons from ionization. In this paper, we report on the first characterization of the single electron response of SPCs with unprecedented precision, using a UV-laser calibration system. The experimental approach and analysis methodology are presented along with various direct applications for the upcoming next phase of the experiment at SNOLAB. These include the continuous monitoring of the detector response and electron drift properties during dark matter search runs, as well as the experimental measurement of the trigger threshold efficiency. We measure a mean ionization energy of W=27.6±0.2 eV in Ne+CH4 (2%) for 2.8 keV x-rays, and demonstrate the feasibility of performing similar precision measurements at sub-keV energies for future gas mixtures to be used for dark matter searches at SNOLAB.

The hydrogen isotopic composition of lake water (δ2Hlw) reflects hydrological processes, which can yield information about evaporation and precipitation changes through time when preserved in lake sediment archives. Unfortunately, few proxies exist that record only δ2Hlw. Instead, most δ2Hlw records represent a mix of aquatic and terrestrial material. Highly branched isoprenoids (HBIs), known to be produced by diatoms in marine and lacustrine settings, may be used as a lake water proxy to directly reconstruct hydroclimate, if the hydrogen isotopic composition of HBIs (δ2HHBI) reflects the δ2Hlw. We test this hypothesis by analyzing 78 sediment samples from 12 lakes in the Adirondack Mountains in New York, for HBI concentrations and δ2H. δ2HHBI was compared to δ2Hlw, which showed an average fractionation (eHBI/lw) of −127.3 ± 15.0‰ (1σ) for all samples in all lakes. Consistency in eHBI/lw between samples implies that δ2HHBI may be used to reconstruct δ2Hlw through time, to help assess how lake systems have changed in the past. Sediment samples collected from deeper (>4 m) zones within the lake had smaller variability in eHBI/lw (±11.9‰, 1σ) than samples from shallower zones, suggesting that eHBI/lw may be sensitive to other factors, such as light availability, which may be related to differences in diatom growth habit (e.g., benthic, planktonic). Similarly, the carbon isotopes of HBIs (δ13CHBI) were higher for sediment samples collected in deeper zones in the lake, suggesting that δ13CHBI can be used to further understand differences in HBI synthesis in diatom communities living in different growth habitats.