Ultrafast time-resolved 2D imaging of laser-driven fast electron transport in solid density matter using an x-ray free electron laser.

High-power, short-pulse laser-driven fast electrons can rapidly heat and ionize a high-density target before it hydrodynamically expands. The transport of such electrons within a solid target has been studied using two-dimensional (2D) imaging of electron-induced Kα radiation. However, it is currently limited to no or picosecond scale temporal resolutions. Here, we demonstrate femtosecond time-resolved 2D imaging of fast electron transport in a solid copper foil using the SACLA x-ray free electron laser (XFEL). An unfocused collimated x-ray beam produced transmission images with sub-micron and ∼10 fs resolutions. The XFEL beam, tuned to its photon energy slightly above the Cu K-edge, enabled 2D imaging of transmission changes induced by electron isochoric heating. Time-resolved measurements obtained by varying the time delay between the x-ray probe and the optical laser show that the signature of the electron-heated region expands at ∼25% of the speed of light in a picosecond duration. Time-integrated Cu Kα images support the electron energy and propagation distance observed with the transmission imaging. The x-ray near-edge transmission imaging with a tunable XFEL beam could be broadly applicable for imaging isochorically heated targets by laser-driven relativistic electrons, energetic protons, or an intense x-ray beam.

Ultrafast multi-cycle terahertz measurements of the electrical conductivity in strongly excited solids.

Key insights in materials at extreme temperatures and pressures can be gained by accurate measurements that determine the electrical conductivity. Free-electron laser pulses can ionize and excite matter out of equilibrium on femtosecond time scales, modifying the electronic and ionic structures and enhancing electronic scattering properties. The transient evolution of the conductivity manifests the energy coupling from high temperature electrons to low temperature ions. Here we combine accelerator-based, high-brightness multi-cycle terahertz radiation with a single-shot electro-optic sampling technique to probe the evolution of DC electrical conductivity using terahertz transmission measurements on sub-picosecond time scales with a multi-undulator free electron laser. Our results allow the direct determination of the electron-electron and electron-ion scattering frequencies that are the major contributors of the electrical resistivity.

Uncaptured rates of postpartum venous thromboembolism: a US national analysis.

OBJECTIVE: To quantify the proportion of postpartum venous thromboembolism (VTE) readmissions, including those that occur at different hospitals from index admission, and describe risk factors for this outcome. DESIGN: Retrospective observational study. SETTING: US hospitals included in the Nationwide Readmissions Database. SAMPLE: A total of 3 719 238 patients >14 years of age with a delivery-associated hospitalisation in 2014. METHODS: Univariate analysis was performed to identify patient and hospital factors associated with readmissions. Significant factors were included in multivariate logistic regression to identify independent risk factors. Results were weighted for national estimates. MAIN OUTCOME MEASURES: Readmission with VTE to both index and different hospitals at 30, 60 and 90 days. RESULTS: The VTE cumulative readmission rate was 0.053% (n = 1477), 0.063% (n = 1765) and 0.069% (n = 1938) at 30, 60 and 90 days, respectively. Patients were readmitted to different hospitals 31% of the time within 90 days. Risk factors for different hospital VTE readmission were unique and included younger age and initial admission to a small/medium-sized hospital. Initial admission to a for-profit hospital increased the likelihood of readmission to a different hospital. CONCLUSIONS: Nearly one in three postpartum VTEs are missed by the current quality metrics, with significant implications for outcomes and quality. For-profit hospitals have a significant portion of their VTE readmissions hidden, falsely lowering their readmission rates relative to public hospitals. TWEETABLE ABSTRACT: US analysis shows 1 in 3 readmissions for postpartum venous thromboembolism currently missed.

2D monochromatic x-ray imaging for beam monitoring of an x-ray free electron laser and a high-power femtosecond laser.

In pump-probe experiments with an X-ray Free Electron Laser (XFEL) and a high-power optical laser, spatial overlap of the two beams must be ensured to probe a pumped area with the x-ray beam. A beam monitoring diagnostic is particularly important in short-pulse laser experiments where a tightly focused beam is required to achieve a relativistic laser intensity for generation of energetic particles. Here, we report the demonstration of on-shot beam pointing measurements of an XFEL and a terawatt class femtosecond laser using 2D monochromatic Kα imaging at the Matter in Extreme Conditions end-station of the Linac Coherent Light Source. A thin solid titanium foil was irradiated by a 25-TW laser for fast electron isochoric heating, while a 7.0 keV XFEL beam was used to probe the laser-heated region. Using a spherical crystal imager (SCI), the beam overlap was examined by measuring 4.51 keV Kα x rays produced by laser-accelerated fast electrons and the x-ray beam. Measurements were made for XFEL-only at various focus lens positions, laser-only, and two-beam shots. Successful beam overlapping was observed on ∼58% of all two-beam shots for 10 µm thick samples. It is found that large spatial offsets of laser-induced Kα spots are attributed to imprecise target positioning rather than shot-to-shot laser pointing variations. By applying the Kα measurements to x-ray Thomson scattering measurements, we found an optimum x-ray beam spot size that maximizes scattering signals. Monochromatic x-ray imaging with the SCI could be used as an on-shot beam pointing monitor for XFEL-laser or multiple short-pulse laser experiments.

Optimization of radiochromic film stacks to diagnose high-flux laser-accelerated proton beams.

Here, we extend flatbed scanner calibrations of GafChromic EBT3, MD-V3, and HD-V2 radiochromic films using high-precision x-ray irradiation and monoenergetic proton bombardment. By computing a visibility parameter based on fractional errors, optimal dose ranges and transitions between film types are identified. The visibility analysis is used to design an ideal radiochromic film stack for the proton energy spectrum expected from the interaction of a petawatt laser with a cryogenic hydrogen jet target.

Setup for meV-resolution inelastic X-ray scattering measurements and X-ray diffraction at the Matter in Extreme Conditions endstation at the Linac Coherent Light Source.

We describe a setup for performing inelastic X-ray scattering and X-ray diffraction measurements at the Matter in Extreme Conditions (MEC) endstation of the Linac Coherent Light Source. This technique is capable of performing high-, meV-resolution measurements of dynamic ion features in both crystalline and non-crystalline materials. A four-bounce silicon (533) monochromator was used in conjunction with three silicon (533) diced crystal analyzers to provide an energy resolution of ∼50 meV over a range of ∼500 meV in single shot measurements. In addition to the instrument resolution function, we demonstrate the measurement of longitudinal acoustic phonon modes in polycrystalline diamond. Furthermore, this setup may be combined with the high intensity laser drivers available at MEC to create warm dense matter and subsequently measure ion acoustic modes.

Whole-exome sequencing is a valuable diagnostic tool for inherited peripheral neuropathies: Outcomes from a cohort of 50 families.

The inherited peripheral neuropathies (IPNs) are characterized by marked clinical and genetic heterogeneity and include relatively frequent presentations such as Charcot-Marie-Tooth disease and hereditary motor neuropathy, as well as more rare conditions where peripheral neuropathy is associated with additional features. There are over 250 genes known to cause IPN-related disorders but it is estimated that in approximately 50% of affected individuals a molecular diagnosis is not achieved. In this study, we examine the diagnostic utility of whole-exome sequencing (WES) in a cohort of 50 families with 1 or more affected individuals with a molecularly undiagnosed IPN with or without additional features. Pathogenic or likely pathogenic variants in genes known to cause IPN were identified in 24% (12/50) of the families. A further 22% (11/50) of families carried sequence variants in IPN genes in which the significance remains unclear. An additional 12% (6/50) of families had variants in novel IPN candidate genes, 3 of which have been published thus far as novel discoveries (KIF1A, TBCK, and MCM3AP). This study highlights the use of WES in the molecular diagnostic approach of highly heterogeneous disorders, such as IPNs, places it in context of other published neuropathy cohorts, while further highlighting associated benefits for discovery.

High-intensity laser-accelerated ion beam produced from cryogenic micro-jet target.

We report on the successful operation of a newly developed cryogenic jet target at high intensity laser-irradiation. Using the frequency-doubled Titan short pulse laser system at Jupiter Laser Facility, Lawrence Livermore National Laboratory, we demonstrate the generation of a pure proton beam a with maximum energy of 2 MeV. Furthermore, we record a quasi-monoenergetic peak at 1.1 MeV in the proton spectrum emitted in the laser forward direction suggesting an alternative acceleration mechanism. Using a solid-density mixed hydrogen-deuterium target, we are also able to produce pure proton-deuteron ion beams. With its high purity, limited size, near-critical density, and high-repetition rate capability, this target is promising for future applications.

A single-shot spatial chirp method for measuring initial AC conductivity evolution of femtosecond laser pulse excited warm dense matter.

To study the rapid evolution of AC conductivity from ultrafast laser excited warm dense matter (WDM), a spatial chirp single-shot method is developed utilizing a crossing angle pump-probe configuration. The pump beam is shaped individually in two spatial dimensions so that it can provide both sufficient laser intensity to excite the material to warm dense matter state and a uniform time window of up to 1 ps with sub-100 fs FWHM temporal resolution. Temporal evolution of AC conductivity in laser excited warm dense gold was also measured.

Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: toward recommendation for molecular testing and management.

SHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had four or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included intrauterine growth restriction (IUGR) <10th percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended.

Reduction of plasma aldosterone and arterial stiffness in obese pre- and stage1 hypertensive subjects after aerobic exercise.

Obesity-related hypertension is associated with increased activity of the renin-angiotensin-aldosterone system (RAAS), increasing arterial stiffness. Aerobic exercise decreases pulse wave velocity (PWV), therefore a treatment option for hypertension and obesity. Assess RAAS activity and PWV before and after 4 weeks of aerobic training in unmedicated, pre-to-stage-1 hypertensives. Ten obese subjects (52±3.2 years, body mass index=33.5±1.4) performed 30 min of aerobic exercise on a treadmill 3 days per week at 65% of peak oxygen consumption (VO2peak). Descriptive characteristics, systolic and diastolic blood pressure (SBP and DBP), PWV, and a blood draw was performed at baseline, following the 4-week control and training interventions. No differences in descriptive characteristics during the control period were observed, however, a significant decrease in plasma aldosterone (ALDO) (255.4±75 to 215.8±66 pg ml(-1), P=0.001), SBP (140±12 to 136±10.4 mm Hg; P=0.02), DBP (89±4.2 to 85±6.3 mm Hg; P=0.03) and central PWV (11.2±0.6 to 9.8±0.8 m s(-1); P=0.04) was shown pre-to-post exercise training. Four weeks of moderate-intensity aerobic training in obese, hypertensives decreases plasma ALDO independently of body weight and is significantly correlated to decreases in PWV reductions.

Setting up an Emergency Medicine Training Program.

This article presents the foundations for building an emergency medicine training program, particularly in an environment with limited resources. It describes the history of the development of EM, what it is, how EM is practised in a typical hospital emergency department and who else is building EM training programs. The experience of establishing EM training in Papua New Guinea provides a model for development in other resource-limited environments. Strategies to establish training and to build the credibility and role of EM within the health system are described.

Breaking the 'harmony' of TNF-α signaling for cancer treatment.

Tumor necrosis factor-alpha (TNF-α) binds to two distinct receptors, TNFR1/p55 and TNFR2/p75. TNF-α is implicated in the processes of tumor growth, survival, differentiation, invasion, metastases, secretion of cytokines and pro-angiogenic factors. We have shown that TNFR2/p75 signaling promotes ischemia-induced angiogenesis via modulation of several angiogenic growth factors. We hypothesized that TNFR2/p75 may promote tumor growth and angiogenesis. Growth of mouse Lewis lung carcinoma (LLC1) and/or mouse melanoma B16 cell was evaluated in wild type (WT), p75 knockout (KO) and double p55KO/p75KO mouse tumor xenograft models. Compared with WT and p55KO/p75KO mice, growth of tumors in p75KO mice was significantly decreased (twofold) in both LLC and B16 tumors. Tumor growth inhibition was correlated with decreases in vascular endothelial growth factor (VEGF) expression and capillary density, as well as bone marrow-derived endothelial progenitor cells incorporation into the functional capillary network, and an increase in apoptotic cells in LLC xenografts. Gene array analysis of tumor tissues showed a decrease in gene expression in pathways that promote tumor angiogenesis and cell survival. Blocking p75 by short-hairpin RNA in cultured LLCs led to increases in TNF-mediated apoptosis, as well as decreases in the constitutive and TNF-mediated expression of angiogenic growth factors (VEGF, HGF, PLGF), and SDF-1α receptor CXCR4. In summary, p75 is essential for tumor angiogenesis and survival in highly vascularized murine lung tumor xenografts. Blocking p75 expression may lead to tumor regression. This may represent new and effective therapy against lung neoplasms and potentially tumors of other origin.

Setting up an Emergency Medicine training program.

MRI is the preferred modality to investigate seizure as diagnostic yield is higher and more specific due to its varied applications. Total of 160 brain MR images of patients suffering from seizure during one year period was evaluated. All seizure cases underwent specific protocol for imaging that targeted hippocampal/mesial temporal lobe imaging.

Lethal acantholytic epidermolysis bullosa due to a novel homozygous deletion in DSP: expanding the phenotype and implications for desmoplakin function in skin and heart.

Desmoplakin is the major linker in desmosomes in epithelia and myocardium, anchoring intermediate filaments by the C-terminus to plakoglobin and plakophilin in the desmosomal plaque. Mutations in the gene DSP encoding desmoplakin have been associated with various phenotypes affecting skin and/or heart. One of these phenotypes, lethal acantholytic epidermolysis bullosa (LAEB), is characterized by extensive postnatal shedding of epidermis leading to early demise and is caused by recessive mutations in the gene DSP resulting in truncation of the desmoplakin C-terminus. Here we describe two infants born to the same consanguinous parents who suffered extensive epidermal dislodgment and died shortly after birth. In addition, universal alopecia, anonychia, malformed ears and cardiomyopathy were observed. As the clinical diagnosis was LAEB, DSP mutation analysis was performed. A homozygous deletion (c.2874del5) abrogating the donor splice site of exon 20 was found. The deletion is predicted to cause read-through in intron 20 with subsequent recognition of a premature termination codon, resulting in desmoplakin lacking its rod domain and C-terminus (p.Lys959MetfsX5). Electron microscopic analysis of skin biopsies showed absence of the desmosomal inner dense plaque and lack of tonofilament insertion. This is the second report of LAEB. These findings suggest DSP mutations as the aetiology of LAEB and cardiomyopathy as part of the phenotype. Furthermore, they indicate that in addition to the desmoplakin C-terminus, the rod domain is dispensable for intrauterine development but is essential for the inner dense plaque of desmosomes.

Long term visual and neurological prognosis in patients with treated and untreated cavernous sinus aneurysms.

OBJECTIVE: To determine the long term visual and neurological outcome of patients diagnosed with cavernous sinus aneurysms (CCAs). METHODS: Prospective follow up for at least five years or until death of 31 retrospectively recruited patients (27 women, 4 men) with treated and untreated CCAs. RESULTS: There were 40 aneurysms in all. Mean age at diagnosis was 60.4 years (range 25 to 86; median 64). The most common symptoms were diplopia (61%), headache (53%), and facial or orbital pain (32%). Fifteen patients (48%) were diagnosed after they developed cranial nerve pareses, four (13%) after they developed carotid-cavernous sinus fistulas (CCFs), and 12 (39%) by neuroimaging studies done for unrelated symptoms. Twenty one patients (68%) had treatment to exclude the aneurysm from circulation, 10 shortly after diagnosis and 11 after worsening symptoms. Immediate complications of treatment occurred in six patients and included neurological impairment, acute ophthalmoparesis, and visual loss. Ten patients (32%) were observed without intervention. Over a mean (SD) follow up period of 11.8 (7.7) years, eight had improvement in symptoms, five remained stable, and eight deteriorated. Among the 10 patients followed without intervention, none improved spontaneously, three remained stable, and seven worsened. CONCLUSIONS: Most treated patients in this series improved or remained stable after treatment, but none improved without treatment. The long term prognosis for treated cases is relatively good, with most complications occurring immediately after the procedure. Endovascular surgery has decreased the morbidity and mortality of treatment so should be considered for any patient with a CCA.

Uptake of psychosocial referrals in an outpatient cancer setting: improving service accessibility via the referral process.

The object of this study was to identify factors which influence the uptake of psychosocial services in an ambulatory cancer setting and to identify potential barriers to the access of support services in the referral process. To this end, 202 individuals attending outpatient clinics of a cancer hospital were randomised to the intervention arm of a study to assess the impact of providing co-ordinated, targeted psychosocial referrals and interventions. Qualitative and quantitative analysis of the reasons for failure to offer services and for nonacceptance of services was undertaken. Individuals accepted 22% of offered services, refused 38% of offered services, indicated that services were in place in 31% of cases, and were not offered 9% of identified services. The major response from patients refusing services was "not now". Female patients ( P < 0.01), and individuals with a moderate to high level of depression ( P = 0.02), were more likely to accept services. A variety of factors impact on decisions on utilisation of support services. Recommendations on how individuals' access to these services might be improved are offered, based on an analysis of the reasons given by patients for refusal.

Could tourist boots act as vectors for disease transmission in Antarctica?

BACKGROUND: Over the last decade there has been a rapid increase in the number of visitors landing at wildlife sites on the Antarctic continent, and concern has been raised that tourists may transmit important pathogens to or between wildlife colonies. The aim of this study was to determine if tourist activities pose a potential threat to Antarctic wildlife, or possibly to human populations through carriage of pathogens on boots. METHODS: In two trips conducted to Antarctica in the summer season of 2000/2001, swabs were collected from tourist boots: prior to landing, to determine baseline level of bacterial flora on the boots (A isolates); immediately on return to the ship, to quantify the level of contamination (B isolates); and after the boots were washed in seawater to determine the recovery of the organisms after cleaning (C isolates). Swabs were cultured for coliforms, and isolates identified using the API system. RESULTS: Twenty organisms resembling coliforms were isolated from 15 of 72 pairs of boots. Two isolates were recovered from group A, 4 from group B, and 14 from group C. Of these 20 isolates, 11 could be identified using the API identification method. The remaining 9 isolates all produced an unknown but identical profile number. CONCLUSION: These results indicate that current practices for cleaning the boots of tourists visiting Antarctic wildlife colonies may not be sufficient to prevent the transmission of pathogens, and indicate that further studies are needed to define the best method of disinfection.

Cerebrovascular disorders in children with the factor V Leiden mutation.

Since 1995, at least 128 children with a cerebrovascular disorder, cerebral palsy, or both and the factor V Leiden mutation have been reported. The majority of these strokes were in the first year of life, many of them in the perinatal period. Two thirds had an additional exogenous risk factor for thrombosis, and 42% had another recognized endogenous prothrombotic risk factor in combination with the mutation. We review the association of the factor V Leiden mutation and a cerebrovascular disorder in children younger than 16 years of age and describe the clinical features of 8 children with cerebral palsy and the Leiden mutation. This mutation should be considered in the evaluation of children with a stroke or its sequelae, including infants with perinatal stroke.