Recent developments in X-ray diffraction/scattering computed tomography for materials science

X-ray diffraction/scattering computed tomography (XDS-CT) methods are a non-destructive class of chemical imaging techniques that have the capacity to provide reconstructions of sample cross-sections with spatially resolved chemical information. While X-ray diffraction CT (XRD-CT) is the most well-established method, recent advances in instrumentation and data reconstruction have seen greater use of related techniques like small angle X-ray scattering CT and pair distribution function CT. Additionally, the adoption of machine learning techniques for tomographic reconstruction and data analysis are fundamentally disrupting how XDS-CT data is processed. The following narrative review highlights recent developments and applications of XDS-CT with a focus on studies in the last five years. This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 2)'

Ready or not? Expectations of faculty and medical students for clinical skills preparation for clerkships

Background: Preclerkship clinical-skills training has received increasing attention as a foundational preparation for clerkships. Expectations among medical students and faculty regarding the clinical skills and level of skill mastery needed for starting clerkships are unknown. Medical students, faculty teaching in the preclinical setting, and clinical clerkship faculty may have differing expectations of students entering clerkships. If students' expectations differ from faculty expectations, students may experience anxiety. Alternately, congruent expectations among students and faculty may facilitate integrated and seamless student transitions to clerkships. Aims: To assess the congruence of expectations among preclerkship faculty, clerkship faculty, and medical students for the clinical skills and appropriate level of clinical-skills preparation needed to begin clerkships. Methods: Investigators surveyed preclinical faculty, clerkship faculty, and medical students early in their basic clerkships at a North American medical school that focuses on preclerkship clinical-skills development. Survey questions assessed expectations for the appropriate level of preparation in basic and advanced clinical skills for students entering clerkships. Results: Preclinical faculty and students had higher expectations than clerkship faculty for degree of preparation in most basic skills. Students had higher expectations than both faculty groups for advanced skills preparation. Conclusions: Preclinical faculty, clerkship faculty, and medical students appear to have different expectations of clinical-skills training needed for clerkships. As American medical schools increasingly introduce clinical-skills training prior to clerkships, more attention to alignment, communication, and integration between preclinical and clerkship faculty will be important to establish common curricular agendas and increase integration of student learning. Clarification of skills expectations may also alleviate student anxiety about clerkships and enhance their learning

Two specific mutations are prevalent causes of recessive retinitis pigmentosa in North American patients of Jewish ancestry.

PURPOSE: Retinitis pigmentosa is a Mendelian disease with a very elevated genetic heterogeneity. Most mutations are responsible for less than 1% of cases, making molecular diagnosis a multigene screening procedure. In this study, we assessed whether direct testing of specific alleles could be a valuable screening approach in cases characterized by prevalent founder mutations. METHODS: We screened 275 North American patients with recessive/isolate retinitis pigmentosa for two mutations: an Alu insertion in the MAK gene and the p.Lys42Glu missense in the DHDDS gene. All patients were unrelated; 35 reported Jewish ancestry and the remainder reported mixed ethnicity. RESULTS: We identified the MAK and DHDDS mutations homozygously in only 2.1% and 0.8%, respectively, of patients of mixed ethnicity, but in 25.7% and 8.6%, respectively, of cases reporting Jewish ancestry. Haplotype analyses revealed that inheritance of the MAK mutation was attributable to a founder effect. CONCLUSION: In contrast to most mutations associated with retinitis pigmentosa-which are, in general, extremely rare-the two alleles investigated here cause disease in approximately one-third of North American patients reporting Jewish ancestry. Therefore, their screening constitutes an alternative procedure to large-scale tests for patients belonging to this ethnic group, especially in time-sensitive situations.Genet Med 17 4, 285-290

Association of New Loci Identified in European Genome-Wide Association Studies with Susceptibility to Type 2 Diabetes in the Japanese

Several novel susceptibility loci for type 2 diabetes have been identified through genome-wide association studies (GWAS) for type 2 diabetes or quantitative traits related to glucose metabolism in European populations. To investigate the association of the 13 new European GWAS-derived susceptibility loci with type 2 diabetes in the Japanese population, we conducted a replication study using 3 independent Japanese case-control studies. locus, had nominal association with type 2 diabetes in the present Japanese samples (P<0.05). locus may be common locus for type 2 diabetes across different ethnicities

Transient Increase in Cyclic AMP Localized to Macrophage Phagosomes

Cyclic AMP (cAMP) regulates many biological processes and cellular functions. The importance of spatially localized intracellular gradients of cAMP is increasingly appreciated. Previous work in macrophages has shown that cAMP is produced during phagocytosis and that elevated cAMP levels suppress host defense functions, including generation of proinflammatory mediators, phagocytosis and killing. However, the spatial and kinetic characteristics of cAMP generation in phagocytosing macrophages have yet to be examined. Using a Förster resonance energy transfer (FRET)-based cAMP biosensor, we measured the generation of cAMP in live macrophages. We detected no difference in bulk intracellular cAMP levels between resting cells and cells actively phagocytosing IgG-opsonized particles. However, analysis with the biosensor revealed a rapid decrease in FRET signal corresponding to a transient burst of cAMP production localized to the forming phagosome. cAMP levels returned to baseline after the particle was internalized. These studies indicate that localized increases in cAMP accompany phagosome formation and provide a framework for a more complete understanding of how cAMP regulates macrophage host defense functions

Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2

<p>Abstract</p> <p>Background</p> <p>Neonates and young infants manifest increased susceptibility to bacterial, viral and fungal lung infections. Previous work has identified a role for eicosanoids in mediating host defense functions of macrophages. This study examines the relationship between alveolar macrophage (AM) host defense and production of lipid mediators during the neonatal period compared to adult AMs.</p> <p>Methods</p> <p>AMs were harvested from young (day 7 and day 14) and adult (~10 week) rats. The functionality of these cells was assessed by examining their ability to phagocytose opsonized targets, produce cytokines, eicosanoids and intracellular cAMP measured by enzyme immunoassays, and gene expression of proteins, enzymes and receptors essential for eicosanoid generation and phagocytosis measured by real time RT-PCR.</p> <p>Results</p> <p>AMs from young animals (day 7 and 14) were defective in their ability to phagocytose opsonized targets and produce tumor necrosis factor (TNF)- α. In addition, young AMs produce more prostaglandin (PG) E₂, a suppressor of host defense, and less leukotriene (LT) B₄, a promoter of host defense. Young AMs express higher levels of enzymes responsible for the production of PGE₂and LTB₄; however, there was no change in the expression of E prostanoid (EP) receptors or LT receptors. Despite the similar EP profiles, young AMs are more responsive to PGE₂as evidenced by their increased production of the important second messenger, cyclic AMP. In addition, young AMs express higher levels of PDE3B and lower levels of PDE4C compared to adult AMs. However, even though the young AMs produced a skewed eicosanoid profile, neither the inhibition of PGE₂by aspirin nor the addition of exogenous LTB₄rescued the defective opsonized phagocytosis. Examination of a receptor responsible for mediating opsonized phagocytosis showed a significant decrease in the gene expression levels of the Fcgamma receptor in young (day 7) AMs compared to adult AMs.</p> <p>Conclusion</p> <p>These results suggest that elevated production of PGE₂and decreased production of LTB₄do not contribute to impaired opsonized macrophage phagocytosis and highlight an important difference between young and adult AMs.</p

The effect of a clinical pharmacist discharge service on medication discrepancies in patients with heart failure

Objective: Heart failure patients are regularly admitted to hospital and frequently use multiple medication. Besides intentional changes in pharmacotherapy, unintentional changes may occur during hospitalisation. The aim of this study was to investigate the effect of a clinical pharmacist discharge service on medication discrepancies and prescription errors in patients with heart failure. Setting: A general teaching hospital in Tilburg, the Netherlands. Method: An open randomized intervention study was performed comparing an intervention group, with a control group receiving regular care by doctors and nurses. The clinical pharmacist discharge service consisted of review of discharge medication, communicating prescribing errors with the cardiologist, giving patients information, preparation of a written overview of the discharge medication and communication to both the community pharmacist and the general practitioner about this medication. Within 6 weeks after discharge all patients were routinely scheduled to visit the outpatient clinic and medication discrepancies were measured. Main outcome measure: The primary endpoint was the frequency of prescription errors in the discharge medication and medication discrepancies after discharge combined. Results: Forty-four patients were included in the control group and 41 in the intervention group. Sixty-eight percent of patients in the control group had at least one discrepancy or prescription error against 39% in the intervention group (RR 0.57 (95% CI 0.37-0.88)). The percentage of medications with a discrepancy or prescription error in the control group was 14.6% and in the intervention group it was 6.1% (RR 0.42 (95% CI 0.27-0.66)). Conclusion: This clinical pharmacist discharge service significantly reduces the risk of discrepancies and prescription errors in medication of patients with heart failure in the 1st month after discharge

Sintering mechanisms of metals under electric currents

International audienceThis chapter concerns the microscopic mechanisms involved in densifi-cation of metallic powders submitted to high electric current pulses like in the SPS technique. Because metallic systems exhibit high electric conductivity, focus is made on evaluating the sensitivity of the densification mechanisms on the current. Thus, a first part is devoted to the influence of electric currents on elementary met-allurgical phenomena (diffusion, plasticity…) which are involved in densification. Then, after recalling the micromechanical models of densification, the SPS kinetics is described, and analyzed in the framework of these models, with emphasis on the role of the current. Finally, theoretical and experimental investigations on electrically induced mechanisms at the scale of the powder particle contacts, are presented: dielectric breakdown of oxide layers, arcs and plasma, Joule overheating, electroplasticity and electromigration. Then, conclusions are drawn on the most probable mechanisms, and on the role of the current