Steam reforming of DOE complex waste simulants

Sandia National Laboratories has worked with Synthetica Technologies and Manufacturing and Technology Conversion International (MTCl) to demonstrate the applicability of their commercial steam reforming technologies for treating DOE low-level mixed wastes. Previously, Synthetica successfully demonstrated destruction of a Sandia formulated lab trash simulant. During November 1994 Synthetica did not adequately process the aqueous halogenated organic liquid mixed waste simulant (MWTP-2110) formulated by the DOE Mixed Waste Integrated Program (MWIP). Testing at MTCl is ongoing and initial results appear to be favorable. Approximately 200 lbs each of the MWIP aqueous halogenated organic liquids (MWTP-2110), and absorbed aqueous and organic liquids (MWTP-3113/3114) simulants have been processed. At 1650{degree}F, destruction efficiencies of greater than 99% were obtained for tetrachloroethylene, toluene, and 1,2 dichlorobenzene. Product cases consisted primarily of H{sub 2}, C0{sub 2}, CO, and CH{sub 4} and had higher heating values of up to 355 BTU/SCF. Conclusions concerning the suitability of the MTCI process for treating DOE mixed wastes will be drawn upon the completion of testing

Analysis of the technical capabilities of DOE sites for disposal of residuals from the treatment of mixed low-level waste

The US Department of Energy (DOE) has stored or expects to generate over the next five years more than 130,000 m{sup 3} of mixed low-level waste (MLLW). Before disposal, MLLW is usually treated to comply with the land disposal restrictions of the Resource Conservation and Recovery Act. Depending on the type of treatment, the original volume of MLLW and the radionuclide concentrations in the waste streams may change. These changes must be taken into account in determining the necessary disposal capacity at a site. Treatment may remove the characteristic in some waste that caused it to be classified as mixed. Treatment of some waste may, by reduction of the mass, increase the concentrations of some transuranic radionuclides sufficiently so that it becomes transuranic waste. In this report, the DOE MLLW streams were analyzed to determine after-treatment volumes and radionuclide concentrations. The waste streams were reclassified as residual MLLW or low-level or transuranic waste resulting from treatment. The volume analysis indicated that about 89,000 m{sup 3} of waste will require disposal as residual MLLW. Fifteen DOE sites were then evaluated to determine their capabilities for hosting disposal facilities for some or all of the residual MLLW. Waste streams associated with about 90% of the total residual MLLW volume are likely to present no significant issues for disposal and require little additional analysis. Future studies should focus on the remaining waste streams that are potentially problematic by examining site-specific waste acceptance criteria, alternative treatment processes, alternative waste forms for disposal, and pending changes in regulatory requirements

A rapid turnaround gene panel for severe autoinflammation: Genetic results within 48 hours

There is an important unmet clinical need for fast turnaround next generation sequencing (NGS) to aid genetic diagnosis of patients with acute and sometimes catastrophic inflammatory presentations. This is imperative for patients who require precise and targeted treatment to prevent irreparable organ damage or even death. Acute and severe hyper- inflammation may be caused by primary immunodeficiency (PID) with immune dysregulation, or more typical autoinflammatory diseases in the absence of obvious immunodeficiency. Infectious triggers may be present in either immunodeficiency or autoinflammation. We compiled a list of 25 genes causing monogenetic immunological diseases that are notorious for their acute first presentation with fulminant inflammation and which may be amenable to specific treatment, including hemophagocytic lymphohistiocytosis (HLH); and autoinflammatory diseases that can present with early-onset stroke or other irreversible neurological inflammatory complications. We designed and validated a pipeline that enabled return of clinically actionable results in hours rather than weeks: the Rapid Autoinflammation Panel (RAP). We demonstrated accuracy of this new pipeline, with 100% sensitivity and 100% specificity. Return of results to clinicians was achieved within 48-hours from receiving the patient's blood or saliva sample. This approach demonstrates the potential significant diagnostic impact of NGS in acute medicine to facilitate precision medicine and save "life or limb" in these critical situations

Spin-liquid-like state in a square lattice antiferromagnet

Collective behavior of spins, frustration-induced strong quantum fluctuations and subtle interplay between competing degrees of freedom in quantum materials can lead to correlated quantum states with fractional excitations that are essential ingredients for establishing paradigmatic models and have immense potential for quantum technologies. Quenched randomness is a new paradigm in elucidating the emergence of spin-liquidlike states in geometrically frustrated magnets. Herein, we report magnetization, specific heat, electron spin resonance, and muon spin resonance studies on a 3d-electron-based square lattice antiferromagnet Sr3CuTa2O9. In this material, S = 1/2 Cu2+ nearest-neighbor ions constitute a two-dimensional square lattice. The negative value of Curie-Weiss temperature, obtained from the Curie-Weiss fit of high-temperature magnetic susceptibility data indicates the presence of antiferromagnetic interaction between Cu2+ moments. Specific heat data show the absence of long-range magnetic ordering down to 64 mK despite a reasonably strong exchange interaction between Cu2+ spins as reflected from a Curie-Weiss temperature of -27 K. The power-law behavior and the data collapse of specific heat and magnetization data evince the emergence of a random-singlet state in Sr3CuTa2O9. The power-law-like spin auto-correlation function and the data collapse of muon polarization asymmetry with longitudinal field dependence of t/({\mu}0H){\gamma} further support credence to the presence of a randomness-induced liquid-like state. Our results suggest that randomness induced by disorder is a viable route to realize quantum spin liquid-like state in this square lattice antiferromagnet

The pediatric glucocorticoid toxicity index

Objectives: To develop a Pediatric glucocorticoid toxicity index (pGTI), a standardized, weighted clinical outcome assessment that measures change in glucocorticoid (GC) toxicity over time. Methods: Fourteen physician experts from 7 subspecialties participated. The physician experts represented multiple subspecialties in which GCs play a major role in the treatment of inflammatory disease: nephrology, rheumatology, oncology, endocrinology, genetics, psychiatry, and maternal-fetal medicine. Nine investigators were from Canada, Europe, or New Zealand, and 5 were from the United States. Group consensus methods and multi-criteria decision analysis were used. The pGTI is an aggregate assessment of GC toxicities that are common, important, and dynamic. These toxicities are organized into health domains graded as minor, moderate, or major and are weighted according to severity. The relative weights were derived by group consensus and multi-criteria decision analysis using the 1000MindsTM software platform. Two quantitative scores comprise the overall toxicity profile derived from pGTI data: (1) the Cumulative Worsening Score; and (2) the Aggregate Improvement Score. The pGTI also includes a qualitative, unweighted record of GC side-effects known as the Damage Checklist, which documents less common toxicities that, although potentially severe, are unlikely to change with varying GC dosing. Results: One hundred and seven (107) toxicity items were included in the pGTI and thirty-two (32) in the Damage Checklist. To assess the degree to which the pGTI corresponds to expert clinical judgement, the investigators ranked 15 cases by clinical judgement from highest to lowest GC toxicity. Expert rankings were then compared to case ranking by the pGTI, yielding excellent agreement (weighted kappa 0.86). The pGTI was migrated to a digital environment following its development and initial validation. The digital platform is designed to ensure ease-of-use in the clinic, rigor in application, and accuracy of scoring. Clinic staff enter vital signs, laboratory results, and medication changes relevant to pGTI scoring. Clinicians record findings for GC myopathy, skin toxicity, mood dysfunction, and infection. The pGTI algorithms then apply the weights to these raw data and calculate scores. Embedded logic accounts for the impact of age- and sex-related reference ranges on several health domains: blood pressure, lipid metabolism, and bone mineral density. Other algorithms account for anticipated changes in the height Z-scores used in the growth domain, thereby addressing a concern unique to GC toxicity in children. The Damage Checklist ensures comprehensive measurement of GC toxicity but does not contribute to pGTI scoring, because the scored domains emphasize manifestations of GC toxicity that are likely to change over the course of a trial. Conclusions: We describe the development and initial evaluation of a weighted, composite toxicity index for the assessment of morbidity related to GC use in children and adolescents. Developing the pGTI digital platform was essential for performing the nuanced calculations necessary to ensure rigor, accuracy, and ease-of-use in both clinic and research settings

Neuroinflammation, autoinflammation, splenomegaly and anemia caused by bi-allelic mutations in IRAK4

We describe a novel, severe autoinflammatory syndrome characterized by neuroinflammation, systemic autoinflammation, splenomegaly, and anemia (NASA) caused by bi-allelic mutations in IRAK4. IRAK-4 is a serine/threonine kinase with a pivotal role in innate immune signaling from toll-like receptors and production of pro-inflammatory cytokines. In humans, bi-allelic mutations in IRAK4 result in IRAK-4 deficiency and increased susceptibility to pyogenic bacterial infections, but autoinflammation has never been described. We describe 5 affected patients from 2 unrelated families with compound heterozygous mutations in IRAK4 (c.C877T (p.Q293*)/c.G958T (p.D320Y); and c.A86C (p.Q29P)/c.161 + 1G>A) resulting in severe systemic autoinflammation, massive splenomegaly and severe transfusion dependent anemia and, in 3/5 cases, severe neuroinflammation and seizures. IRAK-4 protein expression was reduced in peripheral blood mononuclear cells (PBMC) in affected patients. Immunological analysis demonstrated elevated serum tumor necrosis factor (TNF), interleukin (IL) 1 beta (IL-1β), IL-6, IL-8, interferon α2a (IFN-α2a), and interferon β (IFN-β); and elevated cerebrospinal fluid (CSF) IL-6 without elevation of CSF IFN-α despite perturbed interferon gene signature. Mutations were located within the death domain (DD; p.Q29P and splice site mutation c.161 + 1G>A) and kinase domain (p.Q293*/p.D320Y) of IRAK-4. Structure-based modeling of the DD mutation p.Q29P showed alteration in the alignment of a loop within the DD with loss of contact distance and hydrogen bond interactions with IRAK-1/2 within the myddosome complex. The kinase domain mutation p.D320Y was predicted to stabilize interactions within the kinase active site. While precise mechanisms of autoinflammation in NASA remain uncertain, we speculate that loss of negative regulation of IRAK-4 and IRAK-1; dysregulation of myddosome assembly and disassembly; or kinase active site instability may drive dysregulated IL-6 and TNF production. Blockade of IL-6 resulted in immediate and complete amelioration of systemic autoinflammation and anemia in all 5 patients treated; however, neuroinflammation has, so far proven recalcitrant to IL-6 blockade and the janus kinase (JAK) inhibitor baricitinib, likely due to lack of central nervous system penetration of both drugs. We therefore highlight that bi-allelic mutation in IRAK4 may be associated with a severe and complex autoinflammatory and neuroinflammatory phenotype that we have called NASA (neuroinflammation, autoinflammation, splenomegaly and anemia), in addition to immunodeficiency in humans

Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression

Population genomics of domestic and wild yeasts

The natural genetics of an organism is determined by the distribution of sequences of its genome. Here we present one- to four-fold, with some deeper, coverage of the genome sequences of over seventy isolates of the domesticated baker's yeast, _Saccharomyces cerevisiae_, and its closest relative, the wild _S. paradoxus_, which has never been associated with human activity. These were collected from numerous geographic locations and sources (including wild, clinical, baking, wine, laboratory and food spoilage). These sequences provide an unprecedented view of the population structure, natural (and artificial) selection and genome evolution in these species. Variation in gene content, SNPs, indels, copy numbers and transposable elements provide insights into the evolution of different lineages. Phenotypic variation broadly correlates with global genome-wide phylogenetic relationships however there is no correlation with source. _S. paradoxus_ populations are well delineated along geographic boundaries while the variation among worldwide _S. cerevisiae_ isolates show less differentiation and is comparable to a single _S. paradoxus_ population. Rather than one or two domestication events leading to the extant baker's yeasts, the population structure of _S. cerevisiae_ shows a few well defined geographically isolated lineages and many different mosaics of these lineages, supporting the notion that human influence provided the opportunity for outbreeding and production of new combinations of pre-existing variation

Advances in small lasers

M.T.H was supported by an Australian Research council Future Fellowship research grant for this work. M.C.G. is grateful to the Scottish Funding Council (via SUPA) for financial support.Small lasers have dimensions or modes sizes close to or smaller than the wavelength of emitted light. In recent years there has been significant progress towards reducing the size and improving the characteristics of these devices. This work has been led primarily by the innovative use of new materials and cavity designs. This Review summarizes some of the latest developments, particularly in metallic and plasmonic lasers, improvements in small dielectric lasers, and the emerging area of small bio-compatible or bio-derived lasers. We examine the different approaches employed to reduce size and how they result in significant differences in the final device, particularly between metal- and dielectric-cavity lasers. We also present potential applications for the various forms of small lasers, and indicate where further developments are required.PostprintPeer reviewe