Examination of the short-range structure of molten salts: ThF4, UF4, and related alkali actinide fluoride systems.

The short-range structures of LiF-ThF4, NaF-AnF4, KF-AnF4, and Cs-AnF4 (An = Th, U), were probed using in situ high temperature Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy. Signally, the EXAFS spectra of pure molten ThF4 and UF4 were measured for the first time. The data were interpreted with the aid of Molecular Dynamics (MD) and standard fitting of the EXAFS equation. As in related studies, a speciation distribution dominated by [AnFx]4-x (x = 7, 8, 9) coordination complexes was observed. The average coordination number was found to decrease with the increasing size of the alkali cation, and increase with AnF4 content. An average coordination number close to 6, which had not been detected before in melts of alkali actinide fluorides, was seen when CsF was used as solvent.

Flexible sample cell for real-time GISAXS, GIWAXS and XRR: design and construction.

Since the properties of functional materials are highly dependent on their specific structure, and since the structural changes, for example during crystallization, induced by coating and annealing processes are significant, the study of structure and its formation is of interest for fundamental and applied science. However, structure analysis is often limited to ex situ determination of final states due to the lack of specialized sample cells that enable real-time investigations. The lack of such cells is mainly due to their fairly complex design and geometrical restrictions defined by the beamline setups. To overcome this obstacle, an advanced sample cell has been designed and constructed; it combines automated doctor blading, solvent vapor annealing and sample hydration with real-time grazing-incidence wide- and small-angle scattering (GIWAXS/GISAXS) and X-ray reflectivity (XRR). The sample cell has limited spatial requirements and is therefore widely usable at beamlines and laboratory-scale instruments. The cell is fully automatized and remains portable, including the necessary electronics. In addition, the cell can be used by interested scientists in cooperation with the Institute for Crystallography and Structural Physics and is expandable with regard to optical secondary probes. Exemplary research studies are presented, in the form of coating of P3HT:PC61PM thin films, solvent vapor annealing of DRCN5T:PC71BM thin films, and hydration of supported phospholipid multilayers, to demonstrate the capabilities of the in situ cell.

[Treatment of supine position-related obstructive sleep apnea with smartphone applications]. / Therapie rückenlagebezogener obstruktiver Schlafapnoe mittels Smartphone-App.

BACKGROUND: Positional obstructive sleep apnea (POSA) is common in mild and moderate forms of obstructive sleep apnea (OSA). Two smartphone applications (apps) professing to avoid the supine position (SP) are available: for Android the "Apnea Sleep Position Trainer" and for iOS the "SomnoPose-Sleep Position Monitor". The smartphone needs to be attached to the chest to recognize SP, which then triggers a vibration alarm. This is intended to encourage the patient to change position and the vibration stops as soon as SP is left. These apps, however, have not yet undergone a systematic evaluation. METHODS: Adult patients with polysomnographically diagnosed POSA were invited to participate in the study. POSA was defined as an apnea-hypopnea index (AHI) in SP >10, with AHI in a lateral position <10 and doubling of the AHI in SP. After 1 month, a control polysomnography (PSG) was performed and compliance (at least 4 h/night on 5 of 7 days) was evaluated after 6 months by phone. A sufficient therapy was defined as reduction in SP to <10% of the total sleep time and to an overall AHI <10. RESULTS: Although 57 patients entered the study, 24 did not appear to the PSG control; therefore, 33 patients finished the study, of whom 25 were treated successfully. The overall AHI in 33 patients was reduced from 14.5 ± 9.0 to 9.5 ± 12.6 and the time in SP decreased significantly from 71.1 ± 50.5 to 25.4 ± 65.0 min. Compliance among the 25 continuously treated patients after 6 months was 79.2%. CONCLUSION: Both smartphone apps have the capability to prevent PS in POSA patients and can potentially offer a cost-effective option in the treatment of POSA.

Identification of a haplotype associated with cholesterol deficiency and increased juvenile mortality in Holstein cattle.

Over the last decades, several genetic disorders have been discovered in cattle. However, the genetic background of disorders in calves is less reported. Recently, German cattle farmers reported on calves from specific matings with chronic diarrhea and retarded growth of unknown etiology. Affected calves did not respond to any medical treatment and died within the first months of life. These calves were underdeveloped in weight and showed progressive and severe emaciation despite of normal feed intake. Hallmark findings of the blood biochemical analysis were pronounced hypocholesterolemia and deficiency of fat-soluble vitamins. Results of the clinical and blood biochemical examination had striking similarities with findings reported in human hypobetalipoproteinemia. Postmortem examination revealed near-complete atrophy of the body fat reserves including the spinal canal and bone marrow. To identify the causal region, we performed a genome-wide association study with 9 affected and 21,077 control animals genotyped with the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA), revealing a strong association signal on BTA 11. Subsequent autozygosity mapping identified a disease-associated haplotype encompassing 1.01 Mb. The segment of extended homozygosity contains 6 transcripts, among them the gene APOB, which is causal for cholesterol disorders in humans. However, results from multi-sample variant calling of 1 affected and 47 unaffected animals did not detect any putative causal mutation. The disease-associated haplotype has an important adverse effect on calf mortality in the homozygous state when comparing survival rates of risk matings vs. non-risk matings. Blood cholesterol values of animals are significantly associated with the carrier status indicating a codominant inheritance. The frequency of the haplotype in the current Holstein population was estimated to be 4.2%. This study describes the identification and phenotypic manifestation of a new Holstein haplotype characterized by pronounced hypocholesterolemia, chronic emaciation, growth retardation, and increased mortality in young cattle, denominated as cholesterol deficiency haplotype. Our genomic investigations and phenotypic examinations provide additional evidence for a mutation within the APOB gene causing cholesterol deficiency in Holstein cattle.

Characterization of large deletions in the DHCR7 gene.

Pathogenic variants in the DHCR7 gene cause Smith-Lemli-Opitz syndrome (SLOS), a defect of cholesterol biosynthesis resulting in an autosomal recessive congenital metabolic malformation disorder. In approximately 4% of patients, the second mutation remains unidentified. In this study, 12 SLOS patients diagnosed clinically and/or by elevated 7-dehydrocholesterol (7-DHC) have been investigated by customized multiplex ligation-dependent probe amplification (MLPA) analysis, because only one DHCR7 sequence variant has been detected. Two unrelated patients of this cohort carry different large deletions in the DHCR7 gene. One patient showed a deletion of exons 3-6. The second patient has a deletion of exons 1 and 2 (non-coding) and lacks the major part of the promoter. These two patients show typical clinical and biochemical phenotypes of SLOS. Second disease-causing mutations are p.(Arg352Trp) and p.(Thr93Met), respectively. Deletion breakpoints were characterized successfully in both cases. Such large deletions are rare in the DHCR7 gene but will resolve some of the patients in whom a second mutation has not been detected.

LC-MS/MS-based quantification of cholesterol and related metabolites in dried blood for the screening of inborn errors of sterol metabolism.

Smith-Lemli-Opitz syndrome (SLOS) is an inherited metabolic disease in the cholesterol biosynthesis pathway which is characterised by accumulation of 7- and 8-dehydrocholesterol and by reduced cholesterol concentrations in all tissues and body fluids. With this study, we developed a new, rapid, robust and high-throughput tandem mass spectrometric method as routine application for the selective SLOS screening and therapy monitoring in serum and dried blood. After protein precipitation of 10 µL serum or 4.7 mm dried blood spot, the sum of 7- and 8-dehydrocholesterol (DHC) was analysed by rapid chromatography combined with tandem mass spectrometry. Method comparison with GC-MS was performed for 46 serum samples. A comparison between serum and corresponding dried blood spots for DHC and cholesterol was performed with 40 samples from SLOS patients. Concentrations of DHC and cholesterol were analysed in 2 dried blood samples from newborns with SLOS and 100 unaffected newborns. Intra- and inter-assay variabilities ranged between 3.7 and 17.7% for serum and dried blood spots. Significant correlations between the new LC-MS/MS method and GC-MS were determined for DHC (r = 0.937, p < 0.001) and for cholesterol (r = 0.946, p < 0.001). Significant coefficients of correlation between serum and dried blood spot samples above 0.8 were calculated for both analytes. A cut-off value of 5.95 for the ratio of DHC/cholesterol (multiplied by 1000) was found to distinguish newborns diagnosed with SLOS from normal newborns in a retrospective analysis after 5 years. The developed method enables a rapid quantification of the sum parameter 7- and 8-DHC in newborns and SLOS patients under therapy in serum as well as dried blood spot samples.

Perspectives on greenhouse gas emission estimates based on Australian wastewater treatment plant operating data.

Primary operating data were collected from forty-six wastewater treatment plants (WWTPs) located across three states within Australia. The size range of plants was indicatively from 500 to 900,000 person equivalents. Direct and indirect greenhouse gas emissions were calculated using a mass balance approach and default emission factors, based on Australia's National Greenhouse Energy Reporting (NGER) scheme and IPCC guidelines. A Monte Carlo-type combined uncertainty analysis was applied to the some of the key emission factors in order to study sensitivity. The results suggest that Scope 2 (indirect emissions due to electrical power purchased from the grid) dominate the emissions profile for most of the plants (indicatively half to three quarters of the average estimated total emissions). This is only offset for the relatively small number of plants (in this study) that have significant on-site power generation from biogas, or where the water utility purchases grid electricity generated from renewable sources. For plants with anaerobic digestion, inventory data issues around theoretical biogas generation, capture and measurement were sometimes encountered that can skew reportable emissions using the NGER methodology. Typically, nitrous oxide (N(2)O) emissions dominated the Scope 1 (direct) emissions. However, N(2)O still only accounted for approximately 10 to 37% of total emissions. This conservative estimate is based on the 'default' NGER steady-state emission factor, which amounts to 1% of nitrogen removed through biological nitrification-denitrification processing in the plant (or indicatively 0.7 to 0.8% of plant influent total nitrogen). Current research suggests that true N(2)O emissions may be much lower and certainly not steady-state. The results of this study help to place in context research work that is focused on direct emissions from WWTPs (including N(2)O, methane and carbon dioxide of non-biogenic origin). For example, whereas non-biogenic CO(2) contributions are relatively minor, it appears that opportunities to reduce indirect emissions as a result of modest savings in power consumption are at least in the same order as those from reducing N(2)O emissions. To avoid potentially high reportable emissions under NGER guidelines, particularly for methane, the onus is placed on WWTP managers to ensure that accurate plant monitoring operating records are kept.

Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.

STUDY QUESTION: What is the length of the diagnostic delay for endometriosis in Austria and Germany, and what are the reasons for the delay? SUMMARY ANSWER: The diagnostic delay for endometriosis in Austria and Germany is surprisingly long, due to both medical and psychosocial reasons. WHAT IS KNOWN ALREADY: Diagnostic delay of endometriosis is a problematic phenomenon which has been evaluated in several European countries and in the USA, but has not been reported for Germany and Austria. STUDY DESIGN, SIZE, DURATION: A cross-sectional, questionnaire-based multicentre study was conducted in tertiary referral centers in Austria and Germany. From September 2010 to February 2012, 171 patients with histologically confirmed endometriosis were included. PARTICIPANTS, SETTING, METHODS: Patients with a previous history of surgically proven endometriosis, internal diseases such as rheumatic disorders, pain symptoms of other origin, gynecological malignancy or post-menopausal status were excluded from the analysis. Patients with histologically confirmed endometriosis completed a questionnaire about their psychosocial and clinical characteristics and experiences. Of 173 patients, two did not provide informed consent and were excluded from the study. MAIN RESULTS AND THE ROLE OF CHANCE: The median interval from the first onset of symptoms to diagnosis was 10.4 (SD: 7.9) years, and 74% of patients received at least one false diagnosis. Factors such as misdiagnosis, mothers considering menstruation as a negative event and normalization of dysmenorrhea by patients significantly prolonged the diagnostic delay. No association was found between either superficial and deep infiltrating endometriosis or oral contraceptive use and the prolongation of diagnosis. LIMITATIONS AND REASONS FOR CAUTION: There was a possible selection bias due to inclusion of surgically treated patients only. WIDER IMPLICATIONS OF THE FINDINGS: Several factors causing prolongation of diagnosis of endometriosis have been reported to date. The principal factors observed in the present study are false diagnosis and normalization of symptoms. Teaching programs for doctors and public awareness campaigns might reduce diagnostic delay in Central Europe. STUDY FUNDING/COMPETING INTEREST(S): No competing interests exist.

Extended sagittal saw cut significantly reduces fracture load in cementless unicompartmental knee arthroplasty compared to cemented tibia plateaus: an experimental cadaver study.

PURPOSE: Periprosthetic tibial plateau fractures represent a rare but serious complication in unicompartmental knee arthroplasty and are associated with extended sagittal tibial bone cuts. These can occur during the surgery, weaken the posterior cortex of the tibia and are associated with periprosthetic tibial plateau fractures. Although excellent long-term results have been reported with cemented unicompartmental knee arthroplasty, there is high interest in cementless fixation. The aim of the study was to compare fracture loads of cementless and cemented unicompartmental knee arthroplasty. METHODS: Tibial components of the Oxford Uni were implanted in six paired fresh-frozen tibiae with a defined extended saw cut (10°) at the dorsal cortex of each specimen. In one set, surgery was performed with cement fixation, and in the other, cementless components were implanted. Vertical loads were then applied under standardised conditions to fracture the specimens. RESULTS: Median loads of 3.7 (0.7-6.9) kN led to fractures in the cemented group, whereas cementless fixated tibiae fractured with a median load of 1.6 (0.2-4.3) kN (P = 0.02). CONCLUSION: The loading capacity in tibiae with cementless components is significantly less compared to cemented fixation. The results show that in case of an extended sagittal bone cut patients especially those with poor bone quality who are treated with a cementless unicompartmental knee arthroplasty are at higher risk for periprosthetic tibial fractures.

Cardiometabolic health after first pregnancy: Associations with social determinants of health. A nuMoM2b-HHS study.

Study objective: This study sought to evaluate the associations between social determinants of health (SDOH) at the time of first pregnancy and subsequent cardiometabolic health, defined as the development of metabolic syndrome. Design: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study- Monitoring Mothers-to-Be-Heart Health Study) is an ongoing prospective cohort study. Setting: Eight academic medical centers enrolled and continue to follow participants. Participants: 4484 participants followed a mean of 3.2 years from the time of their first pregnancy. Interventions: N/a. Main outcome measure: Unadjusted and adjusted Poisson regression models with robust standard errors were used to obtain relative risks and 95% confidence intervals estimating the risk of metabolic syndrome for each baseline SDOH. In secondary analyses we examined the associations between SDOH and incident hypertension, obesity, and diabetes mellitus. Results: Metabolic syndrome developed in 13.6% of participants. Higher socioeconomic position at the time of pregnancy was associated with lower rates of metabolic syndrome [income > 200% poverty level aRR 0.55 (95% CI, 0.42-0.71), attainment of a bachelor's degree aRR 0.62 (0.46-0.84) or higher aRR 0.50 (0.35-0.71)], while being single [aRR 1.45 (95% CI, 1.18-1.77)] and having low health literacy were associated with a greater risk of metabolic syndrome [aRR 1.98 (95% CI, 1.28-3.07)]. Conclusions: Over a short interval following first pregnancy, participants accumulated high proportions of cardiovascular risk factors and metabolic syndrome, with some risk associated with SDOH. The impact of interventions addressing SDOH in pregnant people on cardiometabolic health should be tested as a means of reducing health inequities at the population level.

ANKAphase: software for single-distance phase retrieval from inline X-ray phase-contrast radiographs.

A computer program named ANKAphase is presented that processes X-ray inline phase-contrast radiographs by reconstructing the projected thickness of the object(s) imaged. The program uses a single-distance non-iterative phase-retrieval algorithm described by David Paganin et al. [(2002), J. Microsc. 206, 33-40]. Allowing for non-negligible absorption in the sample, this method is strictly valid only for monochromatic illumination and single-material objects but tolerates deviations from these conditions, especially polychromaticity. ANKAphase is designed to be applied to tomography data (although it does not perform tomographic reconstruction itself). It can process series of images and perform flat-field and dark-field correction. Written in Java, ANKAphase has an intuitive graphical user interface and can be run either as a stand-alone application or as a plugin to ImageJ, a widely used scientific image-processing program. A description of ANKAphase is given and example applications are shown.

Effect of PaCO2 and PaO2 on lidocaine and articaine toxicity.

Alterations in arterial PaCO2 can influence local anesthetic toxicity. The objective of this study was to evaluate the effect of stress-induced changes in PaCO2 and PaO2 on the seizure threshold of lidocaine and articaine. Lidocaine (2% with 1 : 100,000 epinephrine) or articaine (4% with 1 : 100,000 epinephrine) was administered intravenously under rest or stress conditions to 36 rats separated into 4 groups. Propranolol and prazosin were administered preoperatively to minimize cardiovascular effects of epinephrine. Mean arterial pressure (MAP), heart rate (HR), and arterial pH, PaCO2, and PaO2 were measured. Results showed no differences in MAP, HR, or pH. Stress significantly increased the latency period for the first tonic-clonic seizure induced by a toxic dose of both lidocaine and articaine (P < .05). Seizures were brought on more rapidly by articaine. No significant difference between toxic doses of lidocaine and articaine was noted. Stress raised the seizure threshold dose for both drugs and significantly (P < .01) increased arterial PaO2 from 94.0 ± 1.90 mm Hg to 113.0 ± 2.20 mm Hg, and reduced PaCO2 from 36.0 ± 0.77 mm Hg to 27.0 ± 0.98 mm Hg. In conclusion, reduction in PaCO2 and/or increase in PaO2 raised the seizure threshold of lidocaine and articaine. This study also confirmed that lidocaine and articaine have equipotent central nervous system toxicity.

(+)-alpha-(N-1-phenethyl) urea stereospecifically inhibits Ca2+ - but not ADP-stimulated mitochondrial respiration.

The (+) isomer of alpha-(N-1-phenethyl) urea is a moderately potent inhibitor of Ca2+ -stimulated mitochondrial respiration of 45Ca2+ uptake (50 percent inhibition at 0.18 mM) while having no effect on adenosine diphosphate-stimulated respiration; the (-) isomer is without effect up to 4 mM. beta-Phenethylurea does not inhibit with either stimulus. The data support the involvement of a Ca2+ -specific protein in energized mitochondrial Ca2+ uptake.

Molecular dynamics in liquids: spin-lattice relaxation of nitroxide spin labels.

Time domain pulsed saturation recovery and electron-electron double resonance spectroscopies were used to measure the spin-lattice relaxation rates of the electron and the nitrogen nucleus in nitroxide spin labels in liquids. The rotational correlation time range covered is from picoseconds to milliseconds. These rates are quantitatively explained by isotropic rotational Brownian dynamics, which modulate the interactions between the electron spin and the molecular angular momentum; the nitrogen and electron spins; and the solvent protons with both the electron and the nitrogen spins. This solves a 20-year-old problem that has limited scientific applications of nitroxides.

Coenzyme Q(10) is decreased in fibroblasts of patients with methylmalonic aciduria but not in mevalonic aciduria.

The content of coenzyme Q(10) (CoQ(10)) was examined in skin fibroblasts of 10 patients with mevalonic aciduria (MVA) and of 22 patients with methylmalonic aciduria (MMA). Patients with these inborn errors of metabolism are thought to be at risk for CoQ(10) depletion either by direct inhibition of the proximal pathway of CoQ(10) synthesis (MVA) or indirectly by inhibition of mitochondrial energy metabolism (MMA). We demonstrated that CoQ(10) concentrations were not significantly different from controls in MVA patients, suggesting that there may be upregulatory effects. On the other hand the CoQ(10) content in fibroblasts of patients with MMA was significantly reduced.

A feasibility study on the determination of 90Sr food-chain transfer using stable strontium as a surrogate and neutron activation analysis.

We evaluated the applicability of neutron activation analysis for investigating the potential mobility of 90Sr in a pasture area in Hungary. To measure strontium concentrations, we made use of the 84Sr(n,γ)85Sr radiative capture reaction using neutron activation analysis and performed gamma spectroscopy using Compton-suppression techniques on the resulting 514.0 keV gamma ray. Our values for soil-to-plant transfer factors value of 1.6 (2.2) kg kg-1 were in agreement with recommended values from the ICRP and IAEA, as well as similar studies performed by independent researchers. Our values for plant-to-animal transfer coefficients and concentration ratios varied from suggested values by several orders of magnitude to agreement with other values. Based on our results the utilized transfer of stable strontium could not be regarded as a convenient substitute to help clarify the long-term transfer of radioactive strontium in the environment, because short term dosing was applied. Neutron activation analysis provides a unique niche as a technique with very little chemical processing and short sample analysis times.