Time-resolved X-ray diffraction diagnostic development for the National Ignition Facility.

We present the development of an experimental platform that can collect four frames of x-ray diffraction data along a single line of sight during laser-driven, dynamic-compression experiments at the National Ignition Facility. The platform is comprised of a diagnostic imager built around ultrafast sensors with a 2-ns integration time, a custom target assembly that serves also to shield the imager, and a 10-ns duration, quasi-monochromatic x-ray source produced by laser-generated plasma. We demonstrate the performance with diffraction data for Pb ramp compressed to 150 GPa and illuminated by a Ge x-ray source that produces ∼7 × 1011, 10.25-keV photons/ns at the 400 µm diameter sample.

Optimized x-ray emission from 10 ns long germanium x-ray sources at the National Ignition Facility.

This study investigates methods to optimize quasi-monochromatic, ∼10 ns long x-ray sources (XRS) for time-resolved x-ray diffraction measurements of phase transitions during dynamic laser compression measurements at the National Ignition Facility (NIF). To support this, we produce continuous and pulsed XRS by irradiating a Ge foil with NIF lasers to achieve an intensity of 2 × 1015 W/cm2, optimizing the laser-to-x-ray conversion efficiency. Our x-ray source is dominated by Ge He-α line emission. We discuss methods to optimize the source to maintain a uniform XRS for ∼10 ns, mitigating cold plasma and higher energy x-ray emission lines.

Long duration x-ray source development for x-ray diffraction at the National Ignition Facility.

We present the results of experiments to produce a 10 ns-long, quasi-monochromatic x-ray source. This effort is needed to support time-resolved x-ray diffraction (XRDt) measurements of phase transitions during laser-driven dynamic compression experiments at the National Ignition Facility. To record XRDt of phase transitions as they occur, we use high-speed (∼1 ns) gated hybrid CMOS detectors, which record multiple frames of data over a timescale of a few to tens of ns. Consequently, to make effective use of these imagers, XRDt needs the x-ray source to be narrow in energy and uniform in time as long as the sensors are active. The x-ray source is produced by a laser irradiated Ge foil. Our results indicate that the x-ray source lasts during the whole duration of the main laser pulse. Both time-resolved and time-integrated spectral data indicate that the line emission is dominated by the He-α complex over higher energy emission lines. Time-integrated spectra agree well with a one-dimensional Cartesian simulation using HYDRA that predicts a conversion efficiency of 0.56% when the incident intensity is 2 × 1015 W/cm2 on a Ge backlighter.

Timing characterization of fast hCMOS sensors.

We describe a method of analyzing gate profile data for ultrafast x-ray imagers that allows pixel-by-pixel determination of temporal sensitivity in the presence of substantial background oscillations. With this method, systematic timing errors in gate width and gate arrival time of up to 1 ns (in a 2 ns wide gate) can be removed. In-sensor variations in gate arrival and gate width are observed, with variations in each up to 0.5 ns. This method can be used to estimate the coarse timing of the sensor, even if errors up to several ns are present.

Upgrade of the gated laser entrance hole imager G-LEH-2 on the National Ignition Facility.

A major upgrade has been implemented for the ns-gated laser entrance hole imager on the National Ignition Facility (NIF) to obtain high-quality data for Hohlraum physics study. In this upgrade, the single "Furi" hCMOS sensor (1024 × 448 pixel arrays with two-frame capability) is replaced with dual "Icarus" sensors (1024 × 512 pixel arrays with four-frame capability). Both types of sensors were developed by Sandia National Laboratories for high energy density physics experiments. With the new Icarus sensors, the new diagnostic provides twice the detection area with improved uniformity, wider temporal coverage, flexible timing setup, and greater sensitivity to soft x rays (<2 keV). These features, together with the fact that the diagnostic is radiation hardened and can be operated on the NIF for high neutron yield deuterium-triterium experiments, enable significantly greater return of data per experiment.

Where is the 'wisdom' in wisdom tooth surgery? A review of national and international third molar surgery guidelines.

The objective of this narrative review was to identify and evaluate published international guidelines on mandibular third molars (M3M) and to assess their clinical scope and the validity of the recommendations. The search strategy used data obtained from a variety of sources including MEDLINE, national regulatory bodies, national dental and surgical colleges and associations, and military medical departments. Adherence to clinical guideline development was investigated using the AGREE II instrument (Appraisal of Guidelines for Research and Evaluation). Sixteen guidelines pertaining to M3M were included in this review. The guidelines produced by the Faculty of Dental Surgery of the Royal College of Surgeons of England (FDS RCS) and Scottish Intercollegiate Guidelines Network (SIGN) were recommended as meeting the criteria for use. Seven other guidelines were recommended but required modifications. The AGREE II instrument provides an excellent framework for guideline assessment. Unfortunately, very few guidelines scored highly across all domains and therefore were not believed to be of high quality. Due to the significant lack of structure and variable standards in guideline development, the conclusions and recommendations of these guidelines are compromised. There is a need for organizations involved in developing M3M guidelines to update guidance periodically in order to ensure that the information available to clinicians and patients is accurate and relevant to clinical practice.

The phenotypical implications of immune dysregulation in fragile X syndrome.

BACKGROUND AND PURPOSE: Immune system dysfunction and inflammatory dysregulation have been shown in several animal models of fragile X syndrome (FXS). However, the phenotypical implications of this dysregulation have not been systematically evaluated in a large patient cohort. METHODS: Five thousand seven hundred thirty-six FXS patients from a nationwide health insurance database were identified and compared to 573 600 age- and sex-matched controls. The phenome-wide association studies codes of FXS patients and those without FXS were compared and the false discovery rate was controlled at 0.05 using the Benjamini-Hochberg procedure. RESULTS: In addition to the commonly reported comorbidities of FXS, an over-representation of infectious diseases, including otitis media, cellulitis and abscess of fingers or toes, viral enteritis, candidiasis and pneumonia, was discovered. In addition, there was an under-representation of autoimmune disorders in FXS patients. CONCLUSIONS: Our systematic comorbidity analyses identified immunologically-based phenotypes associated with FXS. Our findings align with previous observations of compromised immunity and phagocytic defects in animal models of FXS. These results suggest the importance of immune-related pathways in FXS patients and their relevance to the FMR1 gene.

Off-pump technique and replacement therapy for coronary artery bypass surgery in a patient with hemophilia B.

Antithrombotic treatment and perioperative management in patients with hemophilia remains a challenge. As life expectancy in these patients is increasing, a concern about cardiovascular diseases is emerging. Herein we present the case of a 68 year-old patient with mild hemophilia B and multivessel coronary disease who underwent coronary artery bypass grafting (CABG) surgery. Off-pump surgery with continuous infusion FIX treatment was performed successfully with stable factor IX levels, and no bleeding or thrombotic complications. There is a paucity of cases reported regarding management of CABG in this population. To our knowledge, this is the first patient with mild hemophilia B that underwent CABG surgery with off-pump technique, that seems to be a secure and effective procedure.

Effects of Drug Policy Changes on Evolution of Molecular Markers of Plasmodium falciparum Resistance to Chloroquine, Amodiaquine, and Sulphadoxine-Pyrimethamine in the South West Region of Cameroon.

BACKGROUND: As a result of the spread of parasites resistant to antimalarial drugs, Malaria treatment guidelines in Cameroon evolved from nonartemisinin monotherapy to artemisinin-based combination therapy. The aim of this study was to assess the effect of these therapy changes on the prevalence of molecular markers of resistance from 2003 to 2013 in Mutengene, Cameroon. METHODOLOGY: Dry blood samples (collected in 2003-2005 and 2009-2013) were used for parasite DNA extraction. Drug resistance genes were amplified by PCR and hybridized with oligonucleotide probes or subjected to restriction digestion. The prevalence of individual marker polymorphisms and haplotypes was compared in these two study periods using the Chi square test. RESULTS: Alleles conferring resistance to 4-aminoquinolines in the Pfcrt 76T and Pfmdr1 86Y, 184F, and 1246Y genotypes showed a significant reduction of 97.0% to 66.9%, 83.6% to 45.2%, 97.3% to 56.0%, and 3.1% to 0.0%, respectively (P < 0.05). No difference was observed in SNPs associated with antifolate drugs resistance 51I, 59R, 108N, or 540E (P > 0.05). Haplotype analysis in the Pfmdr1 gene showed a reduction in the YFD from 75.90% to 42.2%, P < 0.0001, and an increase in the NYD (2.9% to 30.1%; P < 0.0001). CONCLUSIONS: The results indicated a gradual return of the 4-aminoquinoline sensitive genotype while the antifolate resistant genotypes increased to saturation.

A high-speed two-frame, 1-2 ns gated X-ray CMOS imager used as a hohlraum diagnostic on the National Ignition Facility (invited).

A novel x-ray imager, which takes time-resolved gated images along a single line-of-sight, has been successfully implemented at the National Ignition Facility (NIF). This Gated Laser Entrance Hole diagnostic, G-LEH, incorporates a high-speed multi-frame CMOS x-ray imager developed by Sandia National Laboratories to upgrade the existing Static X-ray Imager diagnostic at NIF. The new diagnostic is capable of capturing two laser-entrance-hole images per shot on its 1024 × 448 pixels photo-detector array, with integration times as short as 1.6 ns per frame. Since its implementation on NIF, the G-LEH diagnostic has successfully acquired images from various experimental campaigns, providing critical new information for understanding the hohlraum performance in inertial confinement fusion (ICF) experiments, such as the size of the laser entrance hole vs. time, the growth of the laser-heated gold plasma bubble, the change in brightness of inner beam spots due to time-varying cross beam energy transfer, and plasma instability growth near the hohlraum wall.

Spatial resolution measurements of the advanced radiographic capability x-ray imaging system at energies relevant to Compton radiography.

Compton radiography provides a means to measure the integrity, ρR and symmetry of the DT fuel in an inertial confinement fusion implosion near peak compression. Upcoming experiments at the National Ignition Facility will use the ARC (Advanced Radiography Capability) laser to drive backlighter sources for Compton radiography experiments and will use the newly commissioned AXIS (ARC X-ray Imaging System) instrument as the detector. AXIS uses a dual-MCP (micro-channel plate) to provide gating and high DQE at the 40-200 keV x-ray range required for Compton radiography, but introduces many effects that contribute to the spatial resolution. Experiments were performed at energies relevant to Compton radiography to begin characterization of the spatial resolution of the AXIS diagnostic.

Improving the off-axis spatial resolution and dynamic range of the NIF X-ray streak cameras (invited).

We report simulations and experiments that demonstrate an increase in spatial resolution of the NIF core diagnostic x-ray streak cameras by at least a factor of two, especially off axis. A design was achieved by using a corrector electron optic to flatten the field curvature at the detector plane and corroborated by measurement. In addition, particle in cell simulations were performed to identify the regions in the streak camera that contribute the most to space charge blurring. These simulations provide a tool for convolving synthetic pre-shot spectra with the instrument function so signal levels can be set to maximize dynamic range for the relevant part of the streak record.

An investigation of the clinical experiences of dentists within the national dental foundation training programme in the North West of England.

Objective To investigate the clinical experiences of foundation dentists (FDs) in the North West of England.Methods Three research methods were used: a questionnaire completed by FDs at the end of their training; an analysis of the clinical logs of experience recorded in the educational portfolios; and analysis of NHS Business Services Authority (NHSBSA) activity data for the 12 month period of training of FDs.Results A response rate of 100% (N = 50) was achieved for the questionnaire and complete data for 49 of the 50 FDs was available from the NHSBSA and clinical logs in the educational portfolios.Discussion Trainees were satisfied with the clinical experience and believed their workload and patient mix provided a broad experience of clinical conditions, although 40% felt there were gaps in their clinical experience. There were wide ranges in the number of individual clinical procedures performed by FDs with some providing very few endodontic treatments, crowns, bridges, metal dentures and fissure sealants. There was a statistically significant difference (P <0.0005) in self- reporting of procedures recorded in the portfolio log when compared to the NHSBSA data.Conclusion The results from this study suggest that there is satisfaction amongst FDs with FT, but there is wide range in the level of clinical experience amongst FDs with some gaps which need to be addressed. In order to provide a consistent, cost effective approach to the delivery of FT changes are required to ensure minimum levels of clinical procedures are achieved during FT. The information collected in the training portfolio must be robust in order to make valid judgements on progress.

Regulation of the Embryonic Cell Cycle During Mammalian Preimplantation Development.

The preimplantation development stage of mammalian embryogenesis consists of a series of highly conserved, regulated, and predictable cell divisions. This process is essential to allow the rapid expansion and differentiation of a single-cell zygote into a multicellular blastocyst containing cells of multiple developmental lineages. This period of development, also known as the germinal stage, encompasses several important developmental transitions, which are accompanied by dramatic changes in cell cycle profiles and dynamics. These changes are driven primarily by differences in the establishment and enforcement of cell cycle checkpoints, which must be bypassed to facilitate the completion of essential cell cycle events. Much of the current knowledge in this area has been amassed through the study of knockout models in mice. These mouse models are powerful experimental tools, which have allowed us to dissect the relative dependence of the early embryonic cell cycles on various aspects of the cell cycle machinery and highlight the extent of functional redundancy between members of the same gene family. This chapter will explore the ways in which the cell cycle machinery, their accessory proteins, and their stimuli operate during mammalian preimplantation using mouse models as a reference and how this allows for the usually well-defined stages of the cell cycle to be shaped and transformed during this unique and critical stage of development.

Effects of Type 2 Diabetes on Brain Structure and Cognitive Function: African American-Diabetes Heart Study MIND.

BACKGROUND AND PURPOSE: Rates of type 2 diabetes are higher among African Americans compared with individuals of European ancestry. The purpose of this investigation was to determine the relationship between MR imaging measures of brain structure (volume of GM, WM, WM lesions) and cognitive function in a population of African Americans with type 2 diabetes. These MR imaging measures of brain structure are affected by type 2 diabetes-associated macrovascular and microvascular disease and may be associated with performance on tasks of cognitive function in the understudied African American population. MATERIALS AND METHODS: African Americans with type 2 diabetes enrolled in the African American-Diabetes Heart Study MIND study (n = 263) were evaluated across a broad range of cognitive domains and imaged with brain MR imaging. Associations between cognitive parameters and MR imaging measures of whole-brain GM, WM, and WM lesion volumes were assessed by using adjusted multivariate models. RESULTS: Lower GM volume was associated with poorer performance on measures of general cognitive function, working memory, and executive function. Higher WM lesion volume was associated with poorer performance on a smaller subset of cognitive domains compared with GM volume but included aspects of working memory and executive function. There were no statistically significant associations with WM volume. CONCLUSIONS: Markers of cortical atrophy and WM lesion volume are associated with cognitive function in African Americans with type 2 diabetes. These associations are described in an African American cohort with disease control similar to that of individuals of European ancestry, rather than underserved African Americans with poor access to health care. Interventions to reduce cortical atrophy and WM disease may improve cognitive outcomes in this understudied population.

Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure.

Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes.

United Kingdom nationwide study of avascular necrosis of the jaws including bisphosphonate-related necrosis.

We aimed to record all new patients who presented to departments of oral surgery, oral medicine, and oral and maxillofacial surgery, and to dental hospitals in the UK, with avascular necrosis of the jaws including bisphosphonate-related necrosis (BRONJ) over a 2-year period (1 June 2009-31 May 2011). They were eligible irrespective of age, cause, or coexisting conditions. Data on incidence, clinical characteristics, risk factors, and coexisting conditions were collected. A total of 383 cases were registered: 369 were described as BRONJ, 5 as avascular necrosis, and 9 were unknown. Bisphosphonates had been given orally in 207 (56%), intravenously in 125 (34%), both orally and intravenously in 27 (7%), and was unknown in 9 (2%); one had been given denosumab. The main risk factor was dental extraction, and the mandible was commonly affected. The median duration of administration until onset of BRONJ was 3 years in those treated intravenously and 4 years in those treated orally. Levels of engagement with the study varied between regions, and extrapolation from the 2 most involved (Merseyside and Northern Ireland) found around 8.2-12.8 cases/million/year, which is 508-793 patients/year across the UK. To our knowledge this is one of the first studies to estimate national rates of BRONJ. It confirms that the risk and incidence are low. With changes in trends for antiresorptive bone medication, and increasing numbers of elderly people, it would be useful to repeat the registration in the future.