Multi-GeV Electron Acceleration in Wakefields Strongly Driven by Oversized Laser Spots.

Experiments were performed on laser wakefield acceleration in the highly nonlinear regime. With laser powers P<250 TW and using an initial spot size larger than the matched spot size for guiding, we were able to accelerate electrons to energies E_{max}>2.5 GeV, in fields exceeding 500 GV m^{-1}, with more than 80 pC of charge at energies E>1 GeV. Three-dimensional particle-in-cell simulations show that using an oversized spot delays injection, avoiding beam loss as the wakefield undergoes length oscillation. This enables injected electrons to remain in the regions of highest accelerating fields and leads to a doubling of energy gain as compared to results from using half the focal length with the same laser.

High-resolution inelastic x-ray scattering at the high energy density scientific instrument at the European X-Ray Free-Electron Laser.

We introduce a setup to measure high-resolution inelastic x-ray scattering at the High Energy Density scientific instrument at the European X-Ray Free-Electron Laser (XFEL). The setup uses the Si (533) reflection in a channel-cut monochromator and three spherical diced analyzer crystals in near-backscattering geometry to reach a high spectral resolution. An energy resolution of 44 meV is demonstrated for the experimental setup, close to the theoretically achievable minimum resolution. The analyzer crystals and detector are mounted on a curved-rail system, allowing quick and reliable changes in scattering angle without breaking vacuum. The entire setup is designed for operation at 10 Hz, the same repetition rate as the high-power lasers available at the instrument and the fundamental repetition rate of the European XFEL. Among other measurements, it is envisioned that this setup will allow studies of the dynamics of highly transient laser generated states of matter.

Tumefactive Primary Central Nervous System Vasculitis: Imaging Findings of a Rare and Underrecognized Neuroinflammatory Disease.

Primary central nervous system vasculitis (PCNSV) is a poorly understood neuroinflammatory disease of the CNS affecting the intracranial vasculature. Although PCNSV classically manifests as a multifocal beaded narrowing of the intracranial vessels, some patients may not have angiographic abnormalities. A rare subset of patients with PCNSV present with masslike brain lesions mimicking a neoplasm. In this article, we retrospectively review 10 biopsy-confirmed cases of tumefactive PCNSV (t-PCNSV). All cases of t-PCNSV in our series that underwent CTA or MRA were found to have normal large and medium-sized vessels. T-PCNSV had a variable MR imaging appearance with most cases showing cortical/subcortical enhancing masslike lesion (70%), often with microhemorrhages (80%). Diffusion restriction was absent in all lesions. In summary, normal vascular imaging does not exclude the diagnosis of t-PCNSV. Advanced imaging techniques including MR perfusion and MR spectroscopy failed to demonstrate specific findings for t-PCNSV but assisted in excluding neoplasm in the differential diagnosis. Biopsy remains mandatory for definitive diagnosis.

An approach for the measurement of the bulk temperature of single crystal diamond using an X-ray free electron laser.

We present a method to determine the bulk temperature of a single crystal diamond sample at an X-Ray free electron laser using inelastic X-ray scattering. The experiment was performed at the high energy density instrument at the European XFEL GmbH, Germany. The technique, based on inelastic X-ray scattering and the principle of detailed balance, was demonstrated to give accurate temperature measurements, within [Formula: see text] for both room temperature diamond and heated diamond to 500 K. Here, the temperature was increased in a controlled way using a resistive heater to test theoretical predictions of the scaling of the signal with temperature. The method was tested by validating the energy of the phonon modes with previous measurements made at room temperature using inelastic X-ray scattering and neutron scattering techniques. This technique could be used to determine the bulk temperature in transient systems with a temporal resolution of 50 fs and for which accurate measurements of thermodynamic properties are vital to build accurate equation of state and transport models.

Observation of Laser Power Amplification in a Self-Injecting Laser Wakefield Accelerator.

We report on the depletion and power amplification of the driving laser pulse in a strongly driven laser wakefield accelerator. Simultaneous measurement of the transmitted pulse energy and temporal shape indicate an increase in peak power from 187±11 TW to a maximum of 318±12 TW after 13 mm of propagation in a plasma density of 0.9×10^{18} cm^{-3}. The power amplification is correlated with the injection and acceleration of electrons in the nonlinear wakefield. This process is modeled by including a localized redshift and subsequent group delay dispersion at the laser pulse front.

Risk of Injury According to Attention Deficit Hyperactivity Disorder, Comorbid Mental Illness, and Medication Therapy.

INTRODUCTION: We identify the risk of selected types of injuries among patients with ADHD or ADHD and comorbid mental illness. We also assess whether selected medications used by patients with ADHD increase the risk of comorbid mental illness or influence the association between ADHD and injury. METHODS: A retrospective cohort study design was conducted using medical claims data from the Deseret Mutual Benefit Administrators (DMBA). ADHD diagnosis, injury, medication, and demographic data were extracted from claims files during 2001-2013. Rate ratios were adjusted for age, sex, and calendar year. RESULTS: Patients with ADHD were 7.9 (95% CI 7.6-8.2) times more likely to have psychosis, 5.5 (3.9-7.8) times more likely to have alcohol- or drug-induced psychosis, and 6.0 (5.9-6.2) times more likely to have neurotic or personality disorder. Therapy with amphetamine was positively associated with neurotic or personality disorder (rate ratio=1.08, 1.02-1.15); methylphenidate was negatively associated with neurotic or personality disorder (0.90, 0.84-0.97); and atomoxetine was positively associated with psychosis (1.33, 1.21-1.46), alcohol- or drug-induced psychosis (2.38, 1.04-5.43), and neurotic or personality disorder (2.38, 1.04-5.43). ADHD was associated with an increased risk of injury, with ADHD and comorbid mental illness having a stronger increased risk of injury. Psychostimulants ameliorated the increased risk of injury for patients with ADHD. CONCLUSION: Patients with ADHD have an increased risk of injury, significantly more so for those with ADHD and comorbid mental illness. Psychostimulants can lower the risk of injury among patients with ADHD.

Rayleigh-Taylor instability of an ultrathin foil accelerated by the radiation pressure of an intense laser.

We report experimental evidence for a Rayleigh-Taylor-like instability driven by radiation pressure of an ultraintense (10(21) W/cm(2)) laser pulse. The instability is witnessed by the highly modulated profile of the accelerated proton beam produced when the laser irradiates a 5 nm diamondlike carbon (90% C, 10% H) target. Clear anticorrelation between bubblelike modulations of the proton beam and transmitted laser profile further demonstrate the role of the radiation pressure in modulating the foil. Measurements of the modulation wavelength, and of the acceleration from Doppler-broadening of back-reflected light, agree quantitatively with particle-in-cell simulations performed for our experimental parameters and which confirm the existence of this instability.

Diet and caries-associated bacteria in severe early childhood caries.

Frequent consumption of cariogenic foods and bacterial infection are risk factors for early childhood caries (ECC). This study hypothesized that a short diet survey focused on frequency of foods, categorized by putative cariogenicity, would differentiate severe ECC (S-ECC) from caries-free children. Children's diets were obtained by survey and plaque bacteria detected by PCR from 72 S-ECC and 38 caries-free children. S-ECC children had higher scores for between-meal juice (p < 0.01), solid-retentive foods (p < 0.001), eating frequency (p < 0.005), and estimated food cariogenicity (p < 0.0001) than caries-free children. S-ECC children with lesion recurrence ate fewer putative caries-protective foods than children without new lesions. Streptococcus mutans (p < 0.005), Streptococcus sobrinus (p < 0.005), and Bifidobacteria (p < 0.0001) were associated with S-ECC, and S. mutans with S. sobrinus was associated with lesion recurrence (p < 0.05). S. mutans-positive children had higher food cariogenicity scores. Food frequency, putative cariogenicity, and S. mutans were associated with S-ECC individually and in combination.

Complete temporal characterization of asymmetric pulse compression in a laser wakefield.

We present complete experimental characterization of the temporal shape of an intense ultrashort 200-TW laser pulse driving a laser wakefield. The phase of the pulse was uniquely measured by using (second-order) frequency-resolved optical gating. The pulses are asymmetrically compressed and exhibit a positive chirp consistent with the expected asymmetric self-phase-modulation due to photon acceleration or deceleration in a relativistic plasma wave. The measured pulse duration decreases linearly with increasing length and density of the plasma, in quantitative agreement with the intensity-dependent group velocity variation in the plasma wave.

Near-GeV acceleration of electrons by a nonlinear plasma wave driven by a self-guided laser pulse.

The acceleration of electrons to approximately 0.8 GeV has been observed in a self-injecting laser wakefield accelerator driven at a plasma density of 5.5x10(18) cm(-3) by a 10 J, 55 fs, 800 nm laser pulse in the blowout regime. The laser pulse is found to be self-guided for 1 cm (>10zR), by measurement of a single filament containing >30% of the initial laser energy at this distance. Three-dimensional particle in cell simulations show that the intensity within the guided filament is amplified beyond its initial focused value to a normalized vector potential of a0>6, thus driving a highly nonlinear plasma wave.

Isolated central nervous system posttransplant lymphoproliferative disorder treated with high-dose intravenous methotrexate.

Posttransplant lymphoproliferative disorder (PTLD) is an uncommon neoplastic complication of kidney transplantation, affecting about 1% of recipients. It is generally associated with Epstein-Barr virus (EBV) infection of B-lineage lymphocytes. Central nervous system (CNS) involvement is rare. There is little clinical experience with treatment of CNS PTLD due to the relative rarity of the disease other than reduction or withdrawal of immunosuppression, but it is usually fatal. We describe six patients with renal allografts and histologically proven isolated CNS PTLD. Tissue analysis from the biopsy specimens was positive for EBV material in five of the six patients. All six patients were treated with high-dose intravenous methotrexate (HD IV MTX). Methotrexate was initiated at 8 g/m2, with later adjustments for creatinine clearance. With MTX therapy, four patients have had a sustained complete response, and two had progressive disease and were referred for radiation therapy. This finding suggests a subgroup of patients may benefit from MTX but our case series is inadequate to describe overall efficacy. No unexpected toxicities were encountered in 37 courses of treatment. HD IV MTX chemotherapy should be considered as an alternative for treatment of CNS PTLD.

A new genetic disorder in mitochondrial fatty acid beta-oxidation: ACAD9 deficiency.

The acyl-CoA dehydrogenases are a family of multimeric flavoenzymes that catalyze the alpha,beta -dehydrogenation of acyl-CoA esters in fatty acid beta -oxidation and amino acid catabolism. Genetic defects have been identified in most of the acyl-CoA dehydrogenases in humans. Acyl-CoA dehydrogenase 9 (ACAD9) is a recently identified acyl-CoA dehydrogenase that demonstrates maximum activity with unsaturated long-chain acyl-CoAs. We now report three cases of ACAD9 deficiency. Patient 1 was a 14-year-old, previously healthy boy who died of a Reye-like episode and cerebellar stroke triggered by a mild viral illness and ingestion of aspirin. Patient 2 was a 10-year-old girl who first presented at age 4 mo with recurrent episodes of acute liver dysfunction and hypoglycemia, with otherwise minor illnesses. Patient 3 was a 4.5-year-old girl who died of cardiomyopathy and whose sibling also died of cardiomyopathy at age 21 mo. Mild chronic neurologic dysfunction was reported in all three patients. Defects in ACAD9 mRNA were identified in the first two patients, and all patients manifested marked defects in ACAD9 protein. Despite a significant overlap of substrate specificity, it appears that ACAD9 and very-long-chain acyl-CoA dehydrogenase are unable to compensate for each other in patients with either deficiency. Studies of the tissue distribution and gene regulation of ACAD9 and very-long-chain acyl-CoA dehydrogenase identify the presence of two independently regulated functional pathways for long-chain fat metabolism, indicating that these two enzymes are likely to be involved in different physiological functions.

Necrotizing neurosarcoid: three cases with varying presentations.

BACKGROUND: Neurosarcoid affects approximately 5% of patients with sarcoidosis. A significantly more rare entity, necrotizing sarcoidosis affecting the central nervous system, has been confirmed previously in only three case reports. This paper documents three additional cases of necrotizing neurosarcoid, involving a wide spectrum of central nervous system (CNS) locations. RESULTS: One patient presented to the emergency department after being found unresponsive. The second patient was referred due to hearing loss and the third patient sought care due to weakness and numbness of his left lower extremity. Locations of involvement were diverse and included diffuse leptomeningeal involvement, a cerebellopontine angle mass and a thoracic spinal cord lesion. All patients eventually underwent surgical biopsy, and histologic review of tissue samples revealed necrotizing granulomatous inflammation. Serum ACE levels were available for two of the patients and were within normal limits. Once the diagnosis of necrotizing neurosarcoid was confirmed, all patients were treated with systemic corticosteroid therapy; one patient was also treated with an immunosuppressive agent. CONCLUSIONS: Necrotizing neurosarcoid may occur more commonly than previously described and should be considered in the differential diagnosis of patients without systemic manifestations of sarcoidosis.

Functional regulation of xanthine oxidoreductase expression and localization in the mouse mammary gland: evidence of a role in lipid secretion.

Xanthine oxidoreductase (XOR), a key enzyme of purine metabolism, has been implicated in the secretion of the milk fat droplet in lactating mammary epithelial cells, possibly through structural interactions with other milk fat globule proteins including butyrophilin (Btn) and adipophilin (ADPH). To help determine the mechanism by which XOR is regulated, we examined the expression and localization of XOR in the non-secretory states of late pregnancy and induced involution compared with the state of active secretion. XOR mRNA levels started to increase at mid-pregnancy, turned sharply upwards at the onset of lactation and decreased rapidly with forced involution, indicating transcriptional control of the enzyme level by differentiation and secretory function. During pregnancy and involution the enzyme was diffusely distributed in the cytoplasm, but moved rapidly to the apical membrane of the cells when secretion was activated, where it colocalized with both Btn and ADPH, similar to the situation in the milk fat globule itself. Size-exclusion chromatography of solubilized milk fat globule membrane proteins showed that XOR formed a sulphydryl-bond-dependent complex with Btn and ADPH in the milk fat globule membrane. XOR returned to a diffuse cytoplasmic localization shortly after induced involution, while Btn remained localized to the apical membrane, suggesting that localization of XOR is not dependent on the presence of Btn in the apical membrane. Our findings indicate that the expression and membrane association of XOR in the mammary gland are tightly regulated by secretory activity, and suggest that the apical membrane association of XOR regulates the coupling of lipid droplets to the apical plasma membrane during milk lipid secretion.

Neuropathology of occipital horn syndrome.

Occipital horn syndrome, formerly known as Ehlers-Danlos syndrome type IX or X-linked cutis laxa, is an allelic variant of Menkes' syndrome. Although the clinical symptomatology and systemic pathology findings have been well described in occipital horn syndrome, the neuropathology has not previously been reported. A kindred affected by the X-linked occipital horn syndrome is followed at the University of Alabama at Birmingham. A severely mentally retarded dysmorphic man, who died at the age of 26 years, never gained the ability to walk or talk. Among other findings at autopsy, the patient had the skeletal anomalies previously described with occipital horn syndrome. Neuropathologic findings included neovascularization and extreme reduplication of the cerebral arteries, in conjunction with cystic medial degeneration; bilateral cerebellar hypoplasia; focal cortical dysplasia, and cerebellar heterotopias. These findings are similar to those seen in the brains of patients with Menkes' syndrome, which is not surprising, given the known phenotypic overlap and the proven allelism of occipital horn syndrome with classic Menkes' syndrome.

Histological appearance of a chronically stimulated vagus nerve in a pediatric patient.

Histological analysis of chronically stimulated human vagus nerves is lacking in the literature. In this study, we describe the first microscopic findings in a chronically stimulated left vagus nerve from a pediatric patient. Our results show many histological changes in and around the stimulated nerve with severe demyelination. Further long-term clinical and postmortem examinations of chronically stimulated vagus nerves in both children and adults are needed to ascertain whether prolonged exposure to electrical current can cause clinical dysfunction of this nerve.

Exuberant transverse ligament degeneration causing high cervical myelopathy.

Two patients with cervical myelopathy and C1-C2 retro-odontoid masses were examined. Preoperative magnetic resonance imaging studies suggested soft tissue pannus, as might be seen in rheumatoid arthritis; however, the results of serologic testing for rheumatoid factor were negative in both patients. Intraoperative findings and pathologic examination revealed degenerative fibrocartilage without inflammation or neoplasia. Similar lesions reported in the literature have been described as retro-odontoid disk hernia, damaged transverse ligaments, transverse ligament degeneration, synovial cysts, ganglion cysts, and degenerative articular cysts. These lesions may share a common pathophysiologic origin and represent a single disease process, namely exuberant degeneration of the transverse ligament.

Wisconsin Card Sorting performance in patients with temporal lobe epilepsy: clinical and neuroanatomical correlates.

PURPOSE: A sizable proportion of patients with temporal lobe epilepsy (TLE) display impairments on tests of executive function. Previous studies have suggested several factors that may explain such performance, including the presence of hippocampal sclerosis, electrophysiological disruption to extratemporal regions, and early age of seizure onset. However, no clear determinants have been found that consistently explain such executive dysfunction. The present study investigated the contribution of several clinical variables and temporal lobe neuroanatomic features to performance on the Wisconsin Card Sorting Test (WCST) in a series of patients with TLE. METHODS: Eighty-nine patients with lateralized TLE (47 left, 42 right) were examined. Seventy-two patients from this series underwent anterior temporal lobectomy (ATL). Regression analysis was used to examine the effects of age, education, age at seizure onset, seizure duration, seizure laterality, history of secondary generalized seizures, and MRI-based volumes of the right and left hippocampi on preoperative WCST performance (number of categories completed, perseverative errors). Further univariate analyses examined whether the presence of bilateral hippocampal sclerosis, mesial temporal lobe abnormalities beyond the hippocampus, or temporal neocortical abnormalities affected preoperative WCST performance. In addition, we examined whether becoming seizure free after ATL affected change in WCST performance. RESULTS: Overall regression analysis was not significant. However, an examination of individual partial correlations revealed that patients with a history of secondary generalized seizures performed more poorly on the preoperative WCST than did patients without such history. In addition, patients who were seizure free after ATL did not exhibit better WCST outcome than patients who did not become seizure free. The presence of bilateral hippocampal sclerosis, extrahippocampal mesial temporal atrophy, or temporal neocortical lesions did not affect WCST performance. CONCLUSIONS: These results indicate that the presence of temporal lobe structural abnormalities do not significantly affect executive function as measured by the WCST. The present study does suggests that the critical determinants of WCST performance in patients with TLE lie outside the temporal lobe and likely relate to metabolic disruption to frontostriatal neural network systems.

Dietary determinants of dental caries and dietary recommendations for preschool children.

OBJECTIVES: The purpose of this review, commissioned by the Administration for Children and Families, the Health Resources and Services Administration, the Health Care Financing Administration, and the Department of Agriculture's Food and Nutrition Service, was to update the evidence of the dietary factors that affect dental caries, and subsequently formulate dietary recommendations for preschool children based on principles of cariology. METHODS: Literature on the dental caries process, dietary factors affecting dental caries initiation and progression, and nutrition education and counseling were reviewed and synthesized. Dietary guidelines for children at various ages were then constructed based on the review. RESULTS: Dental caries in preschool children is due to a combination of factors, including colonization of teeth with cariogenic bacteria, type of foods and frequency of exposure of these foods to the cariogenic bacteria, and susceptible teeth. Caries risk is greatest if sugars are consumed at high frequency and are in a form that is retained in the mouth for long periods. Sucrose is the most cariogenic sugar because it can form glucan that enables firm bacterial adhesion to teeth and limits diffusion of acid and buffers in the plaque. There is emerging interest in the effects of tooth development and its role in the future dental caries risk of the child. CONCLUSIONS: Nutrition education and counseling for the purposes of reducing caries in children is aimed at teaching parents the importance of reducing high frequency exposures to obvious and hidden sugars. Guidelines include: avoiding frequent consumption of juice or other sugar-containing drinks in the bottle or sippy cup, discouraging the behavior of a child sleeping with a bottle, promoting noncariogenic foods for snacks, fostering eating patterns consistent with the Food Guide Pyramid, limiting cariogenic foods to mealtimes, rapidly clearing cariogenic foods from the child's oral cavity either by toothbrushing or by consumption of protective foods, and restricting sugar-containing snacks that are slowly eaten (e.g., candy, cough drops, lollipops, suckers). Along with nutritional factors, a comprehensive approach to preventing dental caries in preschool children must include improved general dietary habits, good oral hygiene, appropriate use of fluorides, and access to preventive and restorative dental care.