A 2-4 keV multilayer mirrored channel for the NIF Dante system.

During inertial confinement fusion experiments at the National Ignition Facility (NIF), a capsule filled with deuterium and tritium (DT) gas, surrounded by a DT ice layer and a high-density carbon ablator, is driven to the temperature and densities required to initiate fusion. In the indirect method, 2 MJ of NIF laser light heats the inside of a gold hohlraum to a radiation temperature of 300 eV; thermal x rays from the hohlraum interior couple to the capsule and create a central hotspot at tens of millions degrees Kelvin and a density of 100-200 g/cm3. During the laser interaction with the gold wall, m-band x rays are produced at ∼2.5 keV; these can penetrate into the capsule and preheat the ablator and DT fuel. Preheat can impact instability growth rates in the ablation front and at the fuel-ablator interface. Monitoring the hohlraum x-ray spectrum throughout the implosion is, therefore, critical; for this purpose, a Multilayer Mirror (MLM) with flat response in the 2-4 keV range has been installed in the NIF 37° Dante calorimeter. Precision engineering and x-ray calibration of components mean the channel will report 2-4 keV spectral power with an uncertainty of ±8.7%.

Increased Ion Temperature and Neutron Yield Observed in Magnetized Indirectly Driven D_{2}-Filled Capsule Implosions on the National Ignition Facility.

The application of an external 26 Tesla axial magnetic field to a D_{2} gas-filled capsule indirectly driven on the National Ignition Facility is observed to increase the ion temperature by 40% and the neutron yield by a factor of 3.2 in a hot spot with areal density and temperature approaching what is required for fusion ignition [1]. The improvements are determined from energy spectral measurements of the 2.45 MeV neutrons from the D(d,n)^{3}He reaction, and the compressed central core B field is estimated to be ∼4.9 kT using the 14.1 MeV secondary neutrons from the D(T,n)^{4}He reactions. The experiments use a 30 kV pulsed-power system to deliver a ∼3 µs current pulse to a solenoidal coil wrapped around a novel high-electrical-resistivity AuTa_{4} hohlraum. Radiation magnetohydrodynamic simulations are consistent with the experiment.

Uncertain in the face of change: Lack of contingency shift awareness during extinction is associated with higher fear-potentiated startle and PTSD symptoms in children.

Intolerance of uncertainty is a transdiagnostic risk factor for fear-related disorders and is associated with higher levels of anxiety in children and adolescents. It is unclear how uncertainty relates to development of psychopathology in children who have experienced trauma in early life. The present study used a fear-potentiated startle paradigm in children to examine associations between uncertainty (assessed as unawareness of a change in reinforcement during fear extinction) and symptoms of anxiety and posttraumatic stress disorder (PTSD), as well as startle potentiation to threat and safety cues. Results showed that unaware children had strong positive associations between trauma exposure and PTSD symptoms, whereas aware children did not. Uncertainty interacted with anxiety in that children who were both unaware and had higher anxiety displayed higher fear-potentiated startle to safety cues and did not show discrimination between threat and safety during fear conditioning. These results suggest that anxious children who persist in associating a threat cue with an aversive event during extinction, after repeated presentations of the no longer reinforced conditioned stimulus, may express psychophysiological phenotypes related to PTSD.

Population trends in emergency cancer diagnoses: The role of changing patient case-mix.

BACKGROUND: Diagnosis of cancer through an emergency presentation is associated with worse clinical and patient experience outcomes. The proportion of patients with cancer who are diagnosed through emergency presentations has consequently been introduced as a routine cancer surveillance measure in England. Welcome reductions in this metric have been reported over more than a decade but whether reductions reflect true changes in how patients are diagnosed rather than the changing case-mix of incident cohorts in unknown. METHODS: We analysed 'Routes to Diagnosis' data on cancer patients (2006-2015) and used logistic regression modelling to determine the contribution of changes in four case-mix variables (sex, age, deprivation, cancer site) to time-trends in emergency presentations. RESULTS: Between 2006 and 2015 there was an absolute 4.7 percentage point reduction in emergency presentations (23.8%-19.2%). Changing distributions of the four case-mix variables explained 19.0% of this reduction, leaving 81.0% unexplained. Changes in cancer site case-mix alone explained 16.0% of the total reduction. CONCLUSION: Changes in case-mix (particularly that of cancer sites) account for about a fifth of the overall reduction in emergency presentations. This would support the use of adjustment/standardisation of reported statistics to support their interpretation and help appreciate the influence of case-mix, particularly regarding cancer sites with changing incidence. However, most of the reduction in emergency presentations remains unaccounted for, and likely reflects genuine changes during the study period in how patients were being diagnosed.

Leydig cell insufficiency in hypospermatogenesis: a paracrine effect of activin-inhibin signaling?

Clinical findings and a variety of experimental models indicate that Leydig cell dysfunction accompanies damage to the seminiferous tubules with increasing severity. Most studies support the idea that intratesticular signaling from the seminiferous tubules to Leydig cells regulates steroidogenesis, which is disrupted when hypospermatogenesis occurs. Sertoli cells seem to play a pivotal role in this process. In this review, we summarize relevant clinical and experimental observations and present evidence to support the hypothesis that testicular activin signaling and its regulation by testicular inhibin may link seminiferous tubular dysfunction to reduced testosterone biosynthesis.

Assessment of a rapid liquid-based cytology method for measuring sputum cell counts.

Differential sputum cell counting is not widely available despite proven clinical utility in the management of asthma. We compared eosinophil counts obtained using liquid-based cytology (LBC), a routine histopathological processing method, and the current standard method. Eosinophil counts obtained using LBC were a strong predictor of sputum eosinophilia (≥3%) determined by the standard method suggesting LBC could be used in the management of asthma.

The influence of corporate structure and quality improvement activities on outcome improvement in residential care homes.

OBJECTIVE: To examine the impact of corporate structure and quality improvement (QI) activities on improvements in client-reported and professional indicators between 2007 and 2009. DESIGN: A cross-sectional study using organizational survey and indicator multilevel modelling to test relationships between corporate structure, QI activities and performance improvements on indicators. SETTING: In total, 169 residential care homes for the elderly in the Netherlands. MAIN OUTCOME MEASURES: Change between 2007 and 2009 in client-reported and professional indicators. RESULTS: A middle-size corporate structure was associated with QI. The QI activity 'multidisciplinary team meetings' was positively correlated with the indicator 'safety environment' for somatic and psycho-geriatric care. The QI activities 'educational material' and 'direct work instructions' were associated negatively with the indicator 'availability of personnel' for somatic clients, but positively for psycho-geriatric clients. QI activities such as 'health plan activities', 'clinical lessons' and 'financial activities' had no relationship to improved performance. For psycho-geriatric clients mainly organizational QI activities were positively associated with QI. The mediating role of the corporate structure for performing QI activities appeared stronger for the change in client-reported than for professional indicators. CONCLUSION: This study reveals associations between QI activities and corporate structure and changes in indicator performance. A corporate structure was associated with improvement in client-reported indicators, but less on professional indicators, which assumes a central policy at corporate level with impact on client-reported indicators, in contrast to a more local level approach towards activities that result in QI on professional indicators. Tailoring QI activities at the right managerial level may be important to achieve improvement.

Assessment of risk factors for post-rewarming "rebound hyperthermia" in cardiac arrest patients undergoing therapeutic hypothermia.

INTRODUCTION: The outcomes associated with therapeutic hypothermia (TH) after cardiac arrest, while overwhelmingly positive, may be associated with adverse events. The incidence of post-rewarming rebound hyperthermia (RH) has been relatively unstudied and may worsen survival and neurologic outcome. The purpose of this study was to determine the incidence and risk factors associated with RH as well as its relationship to mortality, neurologic morbidity, and hospital length of stay (LOS). METHODS: A retrospective, observational study was performed of adult patients who underwent therapeutic hypothermia after an out-of-hospital cardiac arrest. Data describing 17 potential risk factors for RH were collected. The primary outcome was the incidence of RH while the secondary outcomes were mortality, discharge neurologic status, and LOS. RESULTS: 141 patients were included. All 17 risk factors for RH were analyzed and no potential risk factors were found to be significant at a univariate level. 40.4% of patients without RH experienced any cause of death during the initial hospitalization compared to 64.3% patients who experienced RH (OR: 2.66; 95% CI: 1.26-5.61; p=0.011). The presence of RH is not associated with an increase in LOS (10.67 days vs. 9.45 days; absolute risk increase=-1.21 days, 95% CI: -1.84 to 4.27; p=0.434). RH is associated with increased neurologic morbidity (p=0.011). CONCLUSIONS: While no potential risk factors for RH were identified, RH is a marker for increased mortality and worsened neurologic morbidity in cardiac arrest patients who have underwent TH.

Value of subtraction MRI in assessing treatment response following image-guided loco-regional therapies for hepatocellular carcinoma.

AIM: To compare contrast-enhanced subtraction magnetic resonance imaging (MRI) with contrast-enhanced standard MRI in assessing treatment response following loco-regional therapies for hepatocellular carcinoma (HCC). METHOD AND MATERIALS: Institutional review board approval was obtained and informed consent was waived for this retrospective study. All patients were analysed from our institution's liver tumour database that had loco-regional HCC therapy and the following: (1) a contrast-enhanced MRI ≤6 weeks post-treatment, (2) an unenhanced T1-weighted high-signal treatment zone (TZ) ≥1 cm, (3) follow-up contrast-enhanced MRI performed ≥6 months post-treatment. Randomized standard and subtraction TZ datasets were independently assessed by three blinded radiology readers for either complete treatment necrosis or residual disease. The standard of reference (SOR) comprised a consensus read by two radiologists with knowledge of the follow-up MRI and all available clinical data. Statistical analyses were performed using receiver operating characteristics (ROC), t-test, and kappa statistic. RESULTS: Twenty-six patients (19 male and seven female patients; mean age 60 years, standard deviation 10.9 years, range 46-88 years) had a total of 45 corresponding HCCs and TZs. For ROC, the area under the curve (AUC) was 0.93 (subtraction protocol) versus 0.90 (standard protocol; p = 0.49). For the t-test, the mean reader confidence level was 4.4, 3.6, and 4.4 (subtraction protocol) versus 3, 3, and 3.7 (standard protocol; p ≤ 0.011). The kappa statistic for reader-to-SOR agreement was 0.83, 0.63, and 0.71 (subtraction protocol) versus 0.51, 0.36, and 0.64 (standard protocol). CONCLUSION: Subtraction MRI significantly improves the reader confidence level in the assessment of treatment response following loco-regional therapies for HCC.

Importance of Fungicide Seed Treatment and Environment on Seedling Diseases of Cotton.

The importance of fungicide seed treatments on cotton was examined using a series of standardized fungicide trials from 1993 to 2004. Fungicide seed treatments increased stands over those from seed not treated with fungicides in 119 of 211 trials. Metalaxyl increased stands compared to nontreated seed in 40 of 119 trials having significant fungicide responses, demonstrating the importance of Pythium spp. on stand establishment. Similarly, PCNB seed treatment increased stands compared to nontreated seed for 44 of 119 trials with a significant response, indicating the importance of Rhizoctonia solani in stand losses. Benefits from the use of newer seed treatment chemistries, azoxystrobin and triazoles, were demonstrated by comparison with a historic standard seed treatment, carboxin + PCNB + metalaxyl. Little to no stand improvement was found when minimal soil temperatures averaged 25°C the first 3 days after planting. Stand losses due to seedling pathogens increased dramatically as minimal soil temperatures decreased to 12°C and rainfall increased. The importance of Pythium increased dramatically as minimal soil temperature decreased and rainfall increased, while the importance of R. solani was not affected greatly by planting environment. These multi-year data support the widespread use of seed treatment fungicides for the control of the seedling disease complex on cotton.

Identification of gene networks modulated by activin in LbetaT2 cells using DNA microarray analysis.

Activins, members of the TGFbeta family of proteins, are widely expressed in a variety of tissues. First identified based on their ability to regulate biosynthesis and secretion of follicle-stimulating hormone (FSH), activins have also been shown to modulate development, cell growth, apoptosis, and inflammation. Despite their many known functions, the precise mechanisms and downstream signaling pathways by which activins mediate their diverse effects remain unknown. We have used a DNA microarray assay to identify genes that are regulated by activin, alone or in combination with gonadotropin-releasing hormone (GnRH), another major regulator of FSH, in a murine gonadotrope-derived cell line (LbetaT2). We used mRNA from these cells to screen Affymetrix Mu74av2 mouse Gene Chip oligonucleotide microarrays, representing approximately 12,400 mouse genes. Treatment of LbetaT2 cells with activin A, a gonadotropin-releasing hormone agonist (GnRHA) or activin A plus GnRHA resulted in alterations in levels of gene expression that ranged in magnitude from 15 to 67-fold. Data analysis identified 268 transcripts that were up- or down-regulated by two-fold or more. Distinct sets of genes were affected by treatment with activin, GnRHA and activin plus GnRHA, suggesting interactions between activin and GnRHA. Changes in expression of seven randomly selected representative genes identified by the microarray technique were confirmed by real-time quantitative PCR and semi-quantitative reverse transcription/PCR (RT/PCR). Modulation of expression of genes by activin suggests that activin may mediate its effects through a variety of signaling pathways.

Testosterone, sex hormone-binding globulin, and body composition in young adult African American and Caucasian men.

This study examined the diurnal variation in circulating total and free testosterone and sex hormone-binding globulin (SHBG) levels in young adult African American and Caucasian men in order to investigate whether there are differences in the secretion of these plasma hormones in populations at different risks of developing prostate cancer as they age. A significant and similar diurnal rhythm for total and free testosterone was found for both groups. Serum levels of total testosterone were 29.4% and 23.9% lower at 8:00 PM than at 8:00 AM in African American and Caucasian men, respectively. Significantly higher serum levels of total testosterone (P<.01) and SHBG (P <.02) were found in the African American than in the Caucasian men in both the morning and evening, whereas free testosterone levels were similar in both groups. The higher SHBG levels appear to have an environmental/metabolic basis in that the waist circumference, waist-to-hip ratio, and fasting insulin concentration were lower (P <.05) in African Americans than in Caucasians. In summary, these data indicate that racial differences in central adiposity in men are established in early adulthood and influence circulating SHBG and thereby testosterone levels. In light of the findings by others that SHBG increases cyclic adenosine monophosphate (cAMP) production in the prostate and that cAMP-dependent protein kinase A is a coactivator of the androgen receptor, these studies provide a possible mechanism by which circulating androgens may contribute to the increased risk for prostate cancer among African American men.

Technical challenges of hepatic venous outflow reconstruction in right lobe adult living donor liver transplantation.

A right lobe graft that is drained by the right hepatic vein (RHV) is obtained by transecting the liver on the right side of the middle hepatic vein (MHV). On occasion, a small RHV that only drains a portion of the right lobe, with the predominant outflow achieved by the MHV, is encountered. If such variation is not recognized while performing right lobe liver transplantation and the RHV only is used for reconstruction, venous outflow obstruction with subsequent graft congestion and eventual graft failure will occur. Additionally, preservation of the main MHV and its branch drainage of the left lobe is crucial to avoid outflow blockage to the remaining segment 4 in the donor. We report 4 cases showing a variant type of small RHV and large MHV branch that drain not only segments 5 and 8, but also segments 6 and 7. These variations were simultaneously associated with a large-caliber inferior RHV that also required reconstruction. The methods used to diagnose such anatomic variations and the techniques for reconstruction in the donor and recipient are described.

Pituitary follistatin and activin gene expression, and the testicular regulation of FSH in the adult Rhesus monkey (Macaca mulatta).

In rats, FSHbeta gene expression and FSH secretion are increased and decreased, respectively, by pituitary activin and follistatin. Because little information is available on the paracrine control of FSH secretion in the primate, follistatin and activin/inhibin beta(B) messenger RNA (mRNA) levels were measured in pituitaries of adult male rhesus monkeys 6 weeks after castration or sham surgery (n = 5/group). Follistatin mRNA was determined by quantitative RT-PCR assay using oligonucleotide primers designed to span exons 3-5 of the human follistatin gene. Activin/inhibin beta(B) mRNA levels were measured by ribonuclease protection. Orchidectomy resulted in a 100-fold increase in plasma FSH concentrations and a 60-fold rise in those of LH. In castrated monkeys, levels of mRNA encoding FSHbeta, LHbeta, alpha- subunit, and GnRH receptor (GnRH-R) were increased 21-, 2.1-, 1.7-, and 1.7-fold, respectively (P < 0.01). Levels of pituitary follistatin and activin/inhibin beta(B) mRNAs, however, were similar in castrated and intact animals. These data suggest that the paracrine control of FSH secretion in the male differs substantially in primates and rodents. Specifically, the relatively greater postcastration rise in FSHbeta gene expression and FSH secretion in the adult male monkey may result because in this species pituitary follistatin gene expression does not increase after orchidectomy, as it does in the rat.

Follistatin production by skin fibroblasts and its regulation by dexamethasone.

Activin and follistatin (FS) appear to play a role in the development of the skin and its appendages, in the inflammatory process, angiogenesis, and in wound healing. Although there is information on the expression of activin subunits and receptors in fibroblasts and keratinocytes, there are no reports on the regulation of FS expression in these cells. In the present study we analyzed the splicing variants of FS mRNAs in fibroblasts from genital and nongenital skin by RT-PCR and northern analysis, and examined the induction of FS mRNA and protein by hormones and growth factors in skin fibroblasts from human and nonhuman primates. FS mRNA was highly expressed in all fibroblast strains with similar expression regardless of donor species (human or monkey), donor age (neonate or adult), or the organ from which the fibroblast strains were established (skin or pituitary, genital or non-genital skin). Moreover, the band density corresponding to FS-288 was <5-10% of the value for FS-315 in skin fibroblasts as in all other tissues examined. Fibroblast FS mRNA and protein production were biphasically regulated by dexamethasone: low concentrations (0.01 and 0.1 nM) increased whereas higher concentrations (>1 nM) suppressed FS expression. On the other hand, androgens, activin and PACAP38 were without effect. These data establish cultured skin fibroblasts as a model to study FS gene expression in humans, and support a role for follistatin in the normal immune response and in the anti-inflammatory actions of glucocorticoids.

Characterization of 3-[(123)I]iodo-L-alpha-methyl tyrosine transport in astrocytes of neonatal rats.

3-[(123)I]Iodo-L-alpha-methyl tyrosine ((123)I-IMT) is used for diagnosis and monitoring of brain tumours by means of single-photon emission tomography. As recently shown, (123)I-IMT is predominantly mediated into rat C6 glioma cells by sodium-independent system L for large neutral amino acids. Until now, (123)I-IMT transport in non-neoplastic glial cells has not been examined. Therefore, the aim of this study was to examine the cellular pathways and precise transport kinetics of (123)I-IMT uptake into astrocytes of neonatal rats. In particular sodium-independent (123)I-IMT transport into neonatal astrocytes was compared with sodium-independent (123)I-IMT uptake into neoplastic rat C6 glioma cells. Competitive inhibition experiments showed that (123)I-IMT is exclusively transported via sodium-independent system L into the neonatal astrocytes (92%). Kinetic analysis of sodium-independent (123)I-IMT uptake into neonatal astrocytes and into C6 glioma cells revealed apparent Michaelis constants K(M) = 13.9 +/- 0.5 microM and K(M) = 33.9 +/- 4.1 microM, respectively, which are in the same range of K(M) values as those recently determined for amino acid transport into neoplastic and non-neoplastic glial cells. Indeed, the K(M) values in the micromolar range correspond to the expression of the LAT-1 subunit of system L both in the neonatal astrocytes and in C6 glioma cells. However, sodium-independent maximum transport velocities (V(max)) differed significantly between neonatal astrocytes and C6 glioma cells (11.1 +/- 0.3 and 39.9 +/- 3.3 nmol/mg protein/10 min, respectively).

Treatment of late-onset tibia vara using afghan percutaneous osteotomy and orthofix external fixation.

The Afghan osteotomy was combined with external fixation on 19 patients (23 extremities) with late-onset tibia vara. The average weight was 258 lb and all patients weighed >95th percentile. The average preoperative deformity was 28.2 degrees. The average intraoperative correction was 27.6 degrees. Average healing time was 141 days. The mean follow-up was 2.7 years. Based on radiographic correction, at long-term follow-up, there were 15 excellent, two fair, and six poor results. The quality of the initial correction was the only significant variable, and it was borderline (p = 0.0587). Complications included loss of alignment, peroneal nerve palsy, superficial pin tract infection, deep infection, and fracture. This method offers a technically simple procedure with a relatively low complication rate. It allows early mobilization and provides the ability to manipulate the correction postoperatively. An excellent long-term outcome is predicated on achieving an acceptable initial correction as determined by intraoperative mechanical axis radiographs.