Observation of microstructure evolution during inertia friction welding using in-situ synchrotron X-ray diffraction.

The widespread use and development of inertia friction welding is currently restricted by an incomplete understanding of the deformation mechanisms and microstructure evolution during the process. Understanding phase transformations and lattice strains during inertia friction welding is essential for the development of robust numerical models capable of determining optimized process parameters and reducing the requirement for costly experimental trials. A unique compact rig has been designed and used in-situ with a high-speed synchrotron X-ray diffraction instrument to investigate the microstructure evolution during inertia friction welding of a high-carbon steel (BS1407). At the contact interface, the transformation from ferrite to austenite was captured in great detail, allowing for analysis of the phase fractions during the process. Measurement of the thermal response of the weld reveals that the transformation to austenite occurs 230 °C below the equilibrium start temperature of 725 °C. It is concluded that the localization of large strains around the contact interface produced as the specimens deform assists this non-equilibrium phase transformation.

A comparison of methods for early prediction of anaerobic biogas potential on biologically treated municipal solid waste.

Anaerobic gas production tests, generically Biochemical Methane Potential (BMP) or Biogas Potential (BP) tests, are often used to assess biodegradability, though long duration limits their utility. This research investigated whether simple modelling approaches could provide a reliable earlier prediction of total biogas production. Data were assessed from a non-automated biogas test on a large number of both fresh and processed municipal solid waste (MSW) samples, sourced from a mechanical biological treatment (MBT) plant. Non-linear models of biogas production curves were useful in identifying a suitable test endpoint, supporting a test duration of 50 days. Biogas production at 50 days (B50) was predicted using the first 14 days of test data, using (a) linear correlation, (b) a new linearisation process, and (c) non-linear kinetic models. Prediction errors were quantified as relative root mean squared error of prediction (rRMSEP), and bias. Predictions from most models were improved by removing the initial exponential increase phase. Linear correlation gave the most precise and accurate predictions at 14 days (rRMSEP = 2.8%, bias under 0.05%) and allowed acceptable prediction (rRMSEP <10%) both at 8 days, and at 6 days using separate correlations for each sample type. Of the other predictions, the new linearisation process gave the lowest rRMSEP (10.6%) at 14 days. More complex non-linear models conferred no advantage in prediction of B50. These results demonstrate that early prediction of anaerobic gas production is possible for a well-optimised test, using only basic equipment and without recourse to external data sources or complex mathematical modelling.

Staff Perceptions of Improving Emergency Care for Children: A Qualitative Study.

The objective of this study was to identify staff perceptions of a service improvement for pediatric emergency care at a university teaching hospital. Semistructured qualitative interviews of stakeholders were conducted, and grounded theory approach was used for analysis. Forty-one interviews were conducted with physicians, nurses, managers, and health care workers. Major themes emerging from the analysis included the physical space of and flow within the pediatric emergency department (ED), impact of technology, staffing in the ED, the effects of frontline pediatricians and emergency physicians managing children in the ED, and the need for and expectations of a pediatric emergency medicine (PEM) consultant. Human interactions among health care providers, leadership, and teaching are considered as equally important as providing the appropriate environment and qualified professionals for improving care for children in the ED. Appointment of a PEM consultant was suggested to provide leadership and education to manage relationships and implement changes. Subsequent to the study, the model of care for PEM was changed, the pediatric care delivery became more integrated with the main ED, and two PEM consultants were appointed to the institution.

A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3.

The Loeys-Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor-ß (TGF-ß) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF-ß signaling. More recently, TGF-ß ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF-ß pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF-ß signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database.

Germline SMARCE1 mutations predispose to both spinal and cranial clear cell meningiomas.

We recently reported SMARCE1 mutations as a cause of spinal clear cell meningiomas. Here, we have identified five further cases with non-NF2 spinal meningiomas and six with non-NF2 cranial meningiomas. Three of the spinal cases and three of the cranial cases were clear cell tumours. We screened them for SMARCE1 mutations and investigated copy number changes in all point mutation-negative samples. We identified two novel mutations in individuals with spinal clear cell meningiomas and three mutations in individuals with cranial clear cell meningiomas. Copy number analysis identified a large deletion of the 5' end of SMARCE1 in two unrelated probands with spinal clear cell meningiomas. Testing of affected and unaffected relatives of one of these individuals identified the same deletion in two affected female siblings and their unaffected father, providing further evidence of incomplete penetrance of meningioma disease in males. In addition, we found loss of SMARCE1 protein in three of 10 paraffin-embedded cranial clear cell meningiomas. Together, these results demonstrate that loss of SMARCE1 is relevant to cranial as well as spinal meningiomas. Our study broadens the spectrum of mutations in the SMARCE1 gene and expands the phenotype to include cranial clear cell meningiomas.

High-sensitivity Raman spectrometer to study pristine and irradiated interstellar ice analogs.

We discuss the novel design of a sensitive, normal-Raman spectrometer interfaced to an ultra-high vacuum chamber (5 × 10(-11) Torr) utilized to investigate the interaction of ionizing radiation with low temperature ices relevant to the solar system and interstellar medium. The design is based on a pulsed Nd:YAG laser which takes advantage of gating techniques to isolate the scattered Raman signal from the competing fluorescence signal. The setup incorporates innovations to achieve maximum sensitivity without detectable heating of the sample. Thin films of carbon dioxide (CO2) ices of 10 to 396 nm thickness were prepared and characterized using both Fourier transform infrared (FT-IR) spectroscopy and HeNe interference techniques. The ν+ and ν- Fermi resonance bands of CO2 ices were observed by Raman spectroscopy at 1385 and 1278 cm(-1), respectively, and the band areas showed a linear dependence on ice thickness. Preliminary irradiation experiments are conducted on a 450 nm thick sample of CO2 ice using energetic electrons. Both carbon monoxide (CO) and the infrared inactive molecular oxygen (O2) products are readily detected from their characteristic Raman bands at 2145 and 1545 cm(-1), respectively. Detection limits of 4 ± 3 and 6 ± 4 monolayers of CO and O2 were derived, demonstrating the unique power to detect newly formed molecules in irradiated ices in situ. The setup is universally applicable to the detection of low-abundance species, since no Raman signal enhancement is required, demonstrating Raman spectroscopy as a reliable alternative, or complement, to FT-IR spectroscopy in space science applications.

On the formation of ozone in oxygen-rich solar system ices via ionizing radiation.

The irradiation of pure molecular oxygen (O(2)) and carbon dioxide (CO(2)) ices with 5 keV H(+) and He(+) ions was investigated experimentally to simulate the chemical processing of oxygen rich planetary and interstellar surfaces by exposure to galactic cosmic ray (GCR), solar wind, and magnetospheric particles. Deposited at 12 K under ultra-high vacuum conditions (UHV), the irradiated condensates were monitored on-line and in situ in the solid-state by Fourier transform infrared spectroscopy (FTIR), revealing the formation of ozone (O(3)) in irradiated oxygen ice; and ozone, carbon monoxide (CO), and cyclic carbon trioxide (c-CO(3)) in irradiated carbon dioxide. In addition to these irradiation products, evolution of gas-phase molecular hydrogen (H(2)), atomic helium (He) and molecular oxygen (O(2)) were identified in the subliming oxygen and carbon dioxide condensates by quadrupole mass spectrometry (QMS). Temporal abundances of the oxygen and carbon dioxide precursors and the observed molecular products were compiled over the irradiation period to develop reaction schemes unfolding in the ices. These reactions were observed to be dependent on the generation of atomic oxygen (O) by the homolytic dissociation of molecular oxygen induced by electronic, S(e), and nuclear, S(n), interaction with the impinging ions. In addition, the destruction of the ozone and carbon trioxide products back to the molecular oxygen and carbon dioxide precursors was promoted over an extended period of ion bombardment. Finally, destruction and formation yields were calculated and compared between irradiation sources (including 5 keV electrons) which showed a surprising correlation between the molecular yields (∼10(-3)-10(-4) molecules eV(-1)) created by H(+) and He(+) impacts. However, energy transfer by isoenergetic, fast electrons typically generated ten times more product molecules per electron volt (∼10(-2)-10(-3) molecules eV(-1)) than exposure to the ions. Implications of these findings to Solar System chemistry are also discussed.

On the interaction of methyl azide (CH3N3) ices with ionizing radiation: formation of methanimine (CH2NH), hydrogen cyanide (HCN), and hydrogen isocyanide (HNC).

Methyl azide (CH(3)N(3)) might be a potential precursor in the synthesis of prebiotic molecules via nonequilibrium reactions on interstellar ices initiated by energetic galactic cosmic rays (GCR) and photons. Here, we investigate the effects of energetic electrons as formed in the track of cosmic ray particles and 193 nm photons with solid methyl azide at 10 K and the inherent formation of methanimine (CH(2)NH), hydrogen cyanide (HCN), and hydrogen isocyanide (HNC). We present a systematic kinetic study and outline feasible reaction pathways to these molecules. These processes might be also important in solar system analogue ices.

Long-term resistance to simulated climate change in an infertile grassland.

Climate shifts over this century are widely expected to alter the structure and functioning of temperate plant communities. However, long-term climate experiments in natural vegetation are rare and largely confined to systems with the capacity for rapid compositional change. In unproductive, grazed grassland at Buxton in northern England (U.K.), one of the longest running experimental manipulations of temperature and rainfall reveals vegetation highly resistant to climate shifts maintained over 13 yr. Here we document this resistance in the form of: (i) constancy in the relative abundance of growth forms and maintained dominance by long-lived, slow-growing grasses, sedges, and small forbs; (ii) immediate but minor shifts in the abundance of several species that have remained stable over the course of the experiment; (iii) no change in productivity in response to climate treatments with the exception of reduction from chronic summer drought; and (iv) only minor species losses in response to drought and winter heating. Overall, compositional changes induced by 13-yr exposure to climate regime change were less than short-term fluctuations in species abundances driven by interannual climate fluctuations. The lack of progressive compositional change, coupled with the long-term historical persistence of unproductive grasslands in northern England, suggests the community at Buxton possesses a stabilizing capacity that leads to long-term persistence of dominant species. Unproductive ecosystems provide a refuge for many threatened plants and animals and perform a diversity of ecosystem services. Our results support the view that changing land use and overexploitation rather than climate change per se constitute the primary threats to these fragile ecosystems.

Mechanistical studies on the formation and destruction of carbon monoxide (CO), carbon dioxide (CO2), and carbon trioxide (CO3) in interstellar ice analog samples.

A series of ice mixtures containing carbon monoxide (CO), carbon dioxide (CO(2)), and molecular oxygen (O(2)) with varying carbon-to-oxygen ratios from 1 : 1.5 to 1 : 4 were irradiated at 10 K with energetic electrons to derive formation mechanisms and destruction pathways of carbon monoxide (CO), carbon dioxide (CO(2)), and carbon trioxide (CO(3)) in extraterrestrial, low temperature ices. Reactants and products were analyzed on line and in situ via absorption-reflection-absorption FTIR spectroscopy in the solid state, while the gas phase was sampled by a quadrupole mass spectrometer (QMS). Additionally, isotopically mixed ices consisting of (i) (13)CO ratio C(18)O ratio CO(2), (ii) CO(2)ratio C(18)O(2), and (iii) CO(2)ratio(18)O(2) were irradiated in order to derive mechanistical and kinetic information on the production and destruction pathways of the following species: (i) (13)CO, C(18)O, CO(2), CO, (13)CO(2), (18)OCO, and (13)CO(3) (C(2v)), (ii) CO(2), C(18)O(2), CO, C(18)O, (18)OCO, CO(3) (C(2v)), OC(18)OO (C(2v)), OC(18)O(2) (C(2v)), (18)OCO(2) (C(2v)), (18)OC(18)OO (C(2v)), and C(18)O(3) (C(2v)), and (iii) CO(2), CO, (18)OCO, C(18)O, and C(18)O(2).

A chemical dynamics, kinetics, and theoretical study on the reaction of the cyano radical (CN; X(2)Sigma+) with phenylacetylene (C6H5CCH; X(1)A1).

The chemical reaction dynamics to form o-, m-, and p-cyanophenylacetylene via the neutral-neutral reaction of ground state cyano radicals with phenylacetylene and D(1)-phenylacetylene were investigated in crossed beam experiments; these studies were combined with kinetics measurements of the rate coefficients at temperatures of 123, 200, and 298 K and supplemented by electronic structure calculations. The data suggest that the reaction is initiated by a barrier-less addition of the electrophilic cyano radical to the o-, m-, or p-position of the aromatic ring. The eventually fragmented via atomic hydrogen elimination to form o-, m-, and p-cyanophenylacetylene via tight exit transition states with the hydrogen atom being ejected almost perpendicularly to the molecular plane of the rotating complex. The overall reaction to form o-, m-, and p-cyanophenylacetylene was found to be exoergic by 89 +/- 18 kJ mol(-1) in nice agreement with the calculations. The o-cyanophenylacetylene isomer is of particular relevance as a potential building block to the formation of nitrogen-substituted didehydronaphthalene molecules in analogy to didehydronaphthalene in Titan's aerosol layers--a pathway hitherto neglected by the planetary science modeling community.

Keeping in touch. Cell phone use in people with schizophrenia disorders.

There is limited research exploring telephone intervention for psychiatric clients; no studies specific to cell phone use have been conducted. This pilot study examined the feasibility and acceptability of cell phone use in individuals with schizophrenia spectrum disorders (SSDs). Ten outpatients with SSDs were provided with previously activated cell phones for 5 months; trained nurses contacted participants weekly. Seven participants completed the 5-month follow-up period. A minority of participants reported difficulty retrieving messages and answering or charging their phone. These preliminary findings indicate the majority of individuals with SSDs are willing to use this method of communication and are able to do so with few problems. Possible barriers to the use of cell phones with this group include lifestyle factors and poor decision making. Future investigations should examine the use of cell phone access to foster personal safety, gain a sense of connectedness to others, and enhance quality of life.

Multimodal x-ray and electron microscopy of the Allende meteorite.

Multimodal microscopy that combines complementary nanoscale imaging techniques is critical for extracting comprehensive chemical, structural, and functional information, particularly for heterogeneous samples. X-ray microscopy can achieve high-resolution imaging of bulk materials with chemical, magnetic, electronic, and bond orientation contrast, while electron microscopy provides atomic-scale spatial resolution with quantitative elemental composition. Here, we combine x-ray ptychography and scanning transmission x-ray spectromicroscopy with three-dimensional energy-dispersive spectroscopy and electron tomography to perform structural and chemical mapping of an Allende meteorite particle with 15-nm spatial resolution. We use textural and quantitative elemental information to infer the mineral composition and discuss potential processes that occurred before or after accretion. We anticipate that correlative x-ray and electron microscopy overcome the limitations of individual imaging modalities and open up a route to future multiscale nondestructive microscopies of complex functional materials and biological systems.

Cranio-osteoarthropathy in sibs.

Primary hypertrophic osteoarthropathy is a condition characterized by clubbing, arthropathy and periostosis of long tubular bones. Three variants of primary hypertrophic osteoarthropathy are distinguished: pachydermoperiostosis, which shows as additional symptom pachydermia; cranio-osteoarthropathy, which has a decreased neurocranium ossification as additional feature; and a secondary form. Primary hypertrophic osteoarthropathy is also genetically heterogeneous, with evidence for both autosomal dominant and autosomal recessive inheritance. We describe two sibs with cranio-osteoarthropathy and briefly review previously reported cases. The present cases demonstrate the phenotypic variability of the condition. The consanguinity in the present family and analysis of previously described cases support autosomal recessive inheritance for cranio-osteoarthropathy.

Ethnic-Specific WRN Mutations in South Asian Werner Syndrome Patients: Potential Founder Effect in Patients with Indian or Pakistani Ancestry.

Werner syndrome is a rare autosomal recessive disorder characterized by multiple features consistent with accelerated aging. It is caused by mutations in the WRN gene, which encodes a RecQ type helicase. To date, more than 70 disease-causing mutations have been reported. While founder mutations and a corresponding relatively high incidence of WS have been reported in Japan and Sardinia, such mutations have not been previously described among patients of South Asian descent. Here we report two novel WRN mutations in three pedigrees. A homozygous c.561A>G mutation in exon 6 was identified both in a pedigree from Kerala, India and in a British patient of Pakistani ancestry. Although c.561A>G does not alter the corresponding amino acid (p.K187K), it creates a cryptic splice site resulting in a 98bp deletion at the mRNA level (r.557-654del98) followed by a frameshift (p.K187fs). These two cases shared the same haplotype across the WRN gene, and were distinct from another Indian Werner patient with a homozygous stop codon mutation, c.2855 C>A (p.S952*) in exon 24. As the Indian population increases and the awareness of Werner syndrome grows, we anticipate that more cases will be identified with these founder mutations among South Asian Werner syndrome patients.

Boot camp translation: a method for building a community of solution.

OBJECTIVE: A crucial yet currently insufficient step in biomedical research is the translation of scientific, evidence-based guidelines and recommendations into constructs and language accessible to every-day patients. By building a community of solution that integrates primary care with public health and community-based organizations, evidence-based medical care can be translated into language and constructs accessible to community members and readily implemented to improve health. METHODS: Using a community-based participatory research approach, the High Plains Research Network (HPRN) and its Community Advisory Council developed a process to translate evidence into messages and dissemination methods to improve health in rural Colorado. This process, called Boot Camp Translation, has brought together various community members, organizations, and primary care practices to build a community of solution to address local health problems. RESULTS: The HPRN has conducted 4 Boot Camp Translations on topics including colon cancer prevention, asthma diagnosis and management, hypertension, and the patient-centered medical home. Thus far, the HPRN has used Boot Camp Translations to engage more than 1000 rural community members and providers. Dissemination of boot camp messaging through the community of solution has led to increased colon cancer screening, improved care for asthma, and increased rates of controlled blood pressure. CONCLUSIONS: Boot Camp Translation successfully engages community members in a process to translate evidence-based medical care into locally relevant and culturally appropriate language and constructs. Boot Camp Translation is an appropriate method for engaging community members in patient-centered outcomes research and may be an appropriate first step in building a local or regional community of solution.

Founder mutations and genotype-phenotype correlations in Meckel-Gruber syndrome and associated ciliopathies.

BACKGROUND: Meckel-Gruber syndrome (MKS) is an autosomal recessive lethal condition that is a ciliopathy. MKS has marked phenotypic variability and genetic heterogeneity, with mutations in nine genes identified as causative to date. METHODS: Families diagnosed with Meckel-Gruber syndrome were recruited for research studies following informed consent. DNA samples were analyzed by microsatellite genotyping and direct Sanger sequencing. RESULTS: We now report the genetic analyses of 87 individuals from 49 consanguineous and 19 non-consanguineous families in an unselected cohort with reported MKS, or an associated severe ciliopathy in a kindred. Linkage and/or direct sequencing were prioritized for seven MKS genes (MKS1, TMEM216, TMEM67/MKS3, RPGRIP1L, CC2D2A, CEP290 and TMEM237) selected on the basis of reported frequency of mutations or ease of analysis. We have identified biallelic mutations in 39 individuals, of which 13 mutations are novel and previously unreported. We also confirm general genotype-phenotype correlations. CONCLUSIONS: TMEM67 was the most frequently mutated gene in this cohort, and we confirm two founder splice-site mutations (c.1546 + 1 G > A and c.870-2A > G) in families of Pakistani ethnic origin. In these families, we have also identified two separate founder mutations for RPGRIP1L (c. 1945 C > T p.R649X) and CC2D2A (c. 3540delA p.R1180SfsX6). Two missense mutations in TMEM67 (c. 755 T > C p.M252T, and c. 1392 C > T p.R441C) are also probable founder mutations. These findings will contribute to improved genetic diagnosis and carrier testing for affected families, and imply the existence of further genetic heterogeneity in this syndrome.

Clinical expression of Menkes disease in females with normal karyotype.

BACKGROUND: Menkes Disease (MD) is a rare X-linked recessive fatal neurodegenerative disorder caused by mutations in the ATP7A gene, and most patients are males. Female carriers are mosaics of wild-type and mutant cells due to the random X inactivation, and they are rarely affected. In the largest cohort of MD patients reported so far which consists of 517 families we identified 9 neurologically affected carriers with normal karyotypes. METHODS: We investigated at-risk females for mutations in the ATP7A gene by sequencing or by multiplex ligation-dependent probe amplification (MLPA). We analyzed the X-inactivation pattern in affected female carriers, unaffected female carriers and non-carrier females as controls, using the human androgen-receptor gene methylation assay (HUMAR). RESULTS: The clinical symptoms of affected females are generally milder than those of affected boys with the same mutations. While a skewed inactivation of the X-chromosome which harbours the mutation was observed in 94% of 49 investigated unaffected carriers, a more varied pattern was observed in the affected carriers. Of 9 investigated affected females, preferential silencing of the normal X-chromosome was observed in 4, preferential X-inactivation of the mutant X chromosome in 2, an even X-inactivation pattern in 1, and an inconclusive pattern in 2. The X-inactivation pattern correlates with the degree of mental retardation in the affected females. Eighty-one percent of 32 investigated females in the control group had moderately skewed or an even X-inactivation pattern. CONCLUSION: The X- inactivation pattern alone cannot be used to predict the phenotypic outcome in female carriers, as even those with skewed X-inactivation of the X-chromosome harbouring the mutation might have neurological symptoms.

Mechanistical studies on the formation of carbon dioxide in extraterrestrial carbon monoxide ice analog samples.

Binary ice mixtures of two carbon monoxide isotopomers, (13)C(16)O and (12)C(18)O, were subjected at 10 K to energetic electrons to investigate the interaction of ionizing radiation with extraterrestrial, carbon monoxide bearing ices. The chemical modifications were monitored on line and in situ via absorption-reflection-absorption Fourier transform infrared spectroscopy as well as in the gas-phase via a quadrupole mass spectrometer. Detected products include two newly formed carbon monoxide isotopomers ((12)C(16)O and (13)C(18)O), carbon dioxide ((12)C(16)O(2), (12)C(18)O(16)O, (12)C(18)O(2), (13)C(16)O(2), (13)C(18)O(16)O, and (13)C(18)O(2)), and dicarbon monoxide ((12)C(13)C(16)O and (13)C(13)C(16)O). Kinetic profiles of carbon monoxide and of carbon dioxide were extracted and fit to derive reaction mechanisms and information on the decomposition of carbon monoxide and on the formation of carbon dioxide in extraterrestrial ice analog samples.