First Dark Matter Search Results from the LUX-ZEPLIN (LZ) Experiment.

The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.

Characterization and calibration of a multilayer coated Wolter optic for an imager on the Z-machine at Sandia National Laboratories.

The need for a time-resolved monochromatic x-ray imaging diagnostic at photon energies >15 keV has motivated the development of a Wolter optic to study x-ray sources on the Z-machine at Sandia National Laboratories. The work is performed in both the LLNL's x-ray calibration facility and SNL's micro-focus x-ray lab. Characterizations and calibrations include alignment, measurement of throughput within the field of view (FOV), the point-spread function within the FOV both in and out of focus, and bandpass in the FOV. These results are compared with ray tracing models, showing reasonable agreement.

Design and raytrace simulations of a multilayer-coated Wolter x-ray optic for the Z machine at Sandia National Laboratories.

Recent breakthroughs in the fabrication of small-radii Wolter optics for astrophysics allow high energy density facilities to consider such optics as novel x-ray diagnostics at photon energies of 15-50 keV. Recently, the Lawrence Livermore National Laboratory, Sandia National Laboratories (SNL), the Smithsonian Astrophysical Observatory, and the NASA Marshall Space Flight Center jointly developed and fabricated the first custom Wolter microscope for implementation in SNL's Z machine with optimized sensitivity at 17.5 keV. To achieve spatial resolution of order 100-200 microns over a field of view of 5 × 5 × 5 mm3 with high throughput and narrow energy bandpass, the geometry of the optic and its multilayer required careful design and optimization. While the geometry mainly influences resolution and the field of view of the diagnostic, the mirror coating determines the spectral response and throughput. Here we outline the details of the design and fabrication process for the first multilayer-coated Wolter I optic for SNL's Z machine (Z Wolter), including its W/Si multilayer, and present results of raytrace simulations completed to predict and verify the performance of the optic.

An x-ray optic calibration facility for high energy density diagnostics.

A facility to calibrate x-ray imaging optics was built at Lawrence Livermore National Laboratory to support high energy density (HED) and inertial confinement fusion (ICF) diagnostics such as those at the National Ignition Facility and the Sandia Z-Machine. Calibration of the spectral reflectivity and resolution of these x-ray diagnostics enable absolute determination of the x-ray flux and wavelengths generated in the HED and ICF experiments. Measurement of the optic point spread function is used to determine spatial resolution of the optic. This facility was constructed to measure (1) the x-ray reflectivity to ±5% over a spectral range from 5 to 60 keV; (2) point spread functions with a resolution of 50 µm (currently) and 13 µm (future) in the image plane; and (3) optic distance relative to the x-ray source and detector to within ±100 µm in each dimension. This article describes the capabilities of the calibration facility, concept of operations, and initial data from selected x-ray optics.

A Wolter imager on the Z machine to diagnose warm x-ray sources.

A new Wolter x-ray imager has been developed for the Z machine to study the emission of warm (>15 keV) x-ray sources. A Wolter optic has been adapted from observational astronomy and medical imaging, which uses curved x-ray mirrors to form a 2D image of a source with 5 × 5 × 5 mm3 field-of-view and measured 60-300-µm resolution on-axis. The mirrors consist of a multilayer that create a narrow bandpass around the Mo Kα lines at 17.5 keV. We provide an overview of the instrument design and measured imaging performance. In addition, we present the first data from the instrument of a Mo wire array z-pinch on the Z machine, demonstrating improvements in spatial resolution and a 350-4100× increase in the signal over previous pinhole imaging techniques.

Prevalence of sexual violence against children and use of social services - seven countries, 2007-2013.

Sexual violence against children erodes the strong foundation that children require for leading healthy and productive lives. Globally, studies show that exposure to violence during childhood can increase vulnerability to a broad range of mental and physical health problems, ranging from depression and unwanted pregnancy to cardiovascular disease, diabetes, and sexually transmitted diseases, including human immunodeficiency virus (HIV). Despite this, in many countries, the extent of sexual violence against children is unknown; estimates are needed to stimulate prevention and response efforts and to monitor progress. Consequently, CDC, as a member of the global public-private partnership known as Together for Girls, collaborated with Cambodia, Haiti, Kenya, Malawi, Swaziland, Tanzania, and Zimbabwe to conduct national household surveys of children and youth aged 13-24 years to measure the extent of violence against children. The lifetime prevalence of experiencing any form of sexual violence in childhood ranged from 4.4% among females in Cambodia to 37.6% among females in Swaziland, with prevalence in most countries greater than 25.0%. In most countries surveyed, the proportion of victims that received services, including health and child protective services, was ≤10.0%. Both prevention and response strategies for sexual violence are needed.

Effects of feeding dry glycerin to early postpartum Holstein dairy cows on lactational performance and metabolic profiles.

Effects of feeding a dry glycerin product (minimal 65% of food grade glycerol, dry powder) to 39 multiparous Holstein dairy cows (19 control and 20 glycerin-supplemented; lactation number = 2.2 +/- 1.3 SD) on feed intake, milk yield and composition, and blood metabolic profiles were investigated. Dry glycerin was fed at 250 g/d as a top dressing (corresponding to 162.5 g of glycerol/d) to the common lactating total mixed ration from parturition to 21 d postpartum. Individual milk was sampled from 2 consecutive milkings weekly and analyzed for components. Blood was sampled from the coccygeal vein at 4, 7, 14, and 21 (+/-0.92, pooled SD) d in milk and analyzed for urea nitrogen, glucose, insulin, nonesterified fatty acids, and beta-hydroxybutyrate. Urine was tested for the acetoacetate level weekly by using Ketostix. Average feed intake, milk yield and components, blood metabolites, and serum insulin concentrations were not affected by dry glycerin supplementation. Glycerin-supplemented cows experienced a more positive energy status (higher concentrations of plasma glucose, lower concentrations of plasma beta-hydroxybutyrate, and lower concentrations of urine ketones), which was observed during the second week of lactation, suggesting that energy availability may have been improved. This glucogenic effect of dry glycerin did not result in an increase in feed intake or milk yield during the first 3 wk of lactation, likely because of the relatively less negative energy status of cows transitioning into lactation. The tendency toward higher milk yield for glycerin-supplemented cows during wk 6 of lactation (52 vs. 46 kg/d) after the supplementation period (dry glycerin was terminated at wk 3 of lactation) suggested a potential benefit of dry glycerin on subsequent milk production, perhaps through changes in metabolism, which requires further investigation.

Functional and radiographic outcome of juvenile osteochondritis dissecans of the knee treated with transarticular arthroscopic drilling.

Management of juvenile osteochondritis dissecans is controversial. The purpose of this study was to evaluate the functional and radiographic outcomes of transarticular arthroscopic drilling for isolated stable, juvenile osteochondritis dissecans lesions of the medial femoral condyle with an intact articular surface after 6 months of nonoperative management had failed. We reviewed 30 affected knees in 23 skeletally immature patients (mean age, 12.3 years; range, 8.5 to 16.1) at an average follow-up of 3.9 years (range, 2.0 to 7.2). Functional outcome was determined using the Lysholm score and radiographic outcome was determined using lesion size, and the radiographic score of Rodegerdts and Gleissner. There was significant improvement in the mean Lysholm score (from 58 to 93). There was significant improvement in the mean lesion size on anteroposterior (4.5 +/- 5.8 mm decrease) and lateral (8.4 +/- 8.1 mm decrease) radiographs. There was also significant improvement in the mean radiographic score (from 3.0 to 1.9). Radiographic healing was achieved in all patients at an average of 4.4 months after drilling (range, 1 to 11 months). Linear regression analysis revealed that younger age was an independent, multivariate predictor of Lysholm score improvement. There were no apparent surgical complications.

CNS energy metabolism as related to function.

Large amounts of energy are required to maintain the signaling activities of CNS cells. Because of the fine-grained heterogeneity of brain and the rapid changes in energy demand, it has been difficult to monitor rates of energy generation and consumption at the cellular level and even more difficult at the subcellular level. Mechanisms to facilitate energy transfer within cells include the juxtaposition of sites of generation with sites of consumption and the transfer of approximately P by the creatine kinase/creatine phosphate and the adenylate kinase systems. There is evidence that glycolysis is separated from oxidative metabolism at some sites with lactate becoming an important substrate. Carbonic anhydrase may play a role in buffering activity-induced increases in lactic acid. Relatively little energy is used for 'vegetative' processes. The great majority is used for signaling processes, particularly Na(+) transport. The brain has very small energy reserves, and the margin of safety between the energy that can be generated and the energy required for maximum activity is also small. It seems probable that the supply of energy may impose a limit on the activity of a neuron under normal conditions. A number of mechanisms have evolved to reduce activity when energy levels are diminished.

[Severe neonatal mitochondrial cytopathy caused by isolated COX defect]. / Citopatía mitocondrial neonatal grave por déficit aislado de COX.

We report a neonate with isolated cytochrome c oxidase (COX) defect and severe multisystemic involvement. The patient had severe encephalopathy, predominant since birth, and died due to hypoxic-ischemic myocardiopathy. He was the second son of non-consanguineous, healthy parents who also had a daughter with chronic encephalopathy. The neonate presented dysmorphic phenotype, hepatic and muscular involvement, and possibly tubular involvement. Metabolic studies revealed markedly increased lactic/pyruvic concentrations. Diagnosis was based on muscular enzymatic studies and ultrastructural mitochondrial anomalies, while the mitochondrial DNA and results of the COX technique were normal. Histological examination revealed a massive subendocardial infarction. Aspects of this entity with relevance for genetic counseling are discussed.

Citopatía mitocondrial neonatal grave por déficit aislado de Cox / Severe neonatal mitochondrial cytopathy due to isolated Cox defects

Recién nacido con déficit aislado de citocromo C oxidasa (COX), con afectación multisistémica grave, en la que predominaba desde el nacimiento una encefalopatía severa, que falleció precozmente por miocardiopatía hipóxico-isquémica. Segundo hijo de un matrimonio sano no consanguíneo, con otra hija afectada de encefalopatía crónica. Presentaba además, fenotipo dismórfico, afectación hepática y muscular y una posible tubulopatía. En la valoración metabólica resaltaba una relación láctico/pirúvico aumentada. El diagnóstico se estableció por estudio enzimático muscular y por las alteraciones ultraestructurales mitocondriales, siendo normales el ADNmt y la tinción para COX. En el examen anatomopatológico se evidenció un infarto subendocárdico masivo. Se comentan aspectos de interés sobre esta entidad, dada la importancia de su conocimiento para el correspondiente consejo genético (AU)

A new era in home care.

Profound changes in policy and reimbursement are ushering in a new era in home care. The transition from fee-for-service reimbursement to prospective payment/managed care and the mandate for outcomes assessment provide opportunities to expand innovative home care models. The authors describe 3 such models: community-based long-term care (exemplified by PACE, Program of All-inclusive Care for the Elderly), home-based primary care (exemplified by the Veterans Administration Home-Based Primary Care program), and disease management programs (exemplified by Group Health Cooperative of Puget Sound). Professional qualifications for the new era, including certification and graduate education for advanced practice nursing, also are described.

An in vitro rabbit retina model to study electrophysiologic and metabolic function during and following ischemia.

Most in vitro studies involving neuronal ischemia use biochemical measures and/or cell counting to assess cellular death. We describe an in vitro rabbit retina model in which we measured glucose utilization, lactate production, and light-evoked compound action potentials (CAPs) to assess metabolic and functional recovery following ischemia. Under control conditions, retinal glucose utilization and lactate production (n = 7), as well as CAPs (n = 8) remained quite constant for 6-8 h. During ischemia (glucose reduced from 6 to 1 mM and oxygen from 95 to 15%), glucose utilization and lactate production fell to 50%. CAPs fell to 50% in 3-4 min, and to 0% in 8-10 min. Recovery during 3-4 h of 'return-to-control' was dependent upon the length of ischemia. Glucose utilization recovered to 63% after 1 h (n = 4) and to 18% after 2 h of ischemia (n = 6, P < 0.001). Lactate production recovered to 77% after 1 h (n = 4) and to 54% after 2 h of ischemia (n = 6, P < 0.001). CAPs returned to 51, 15, and 0.13% of the control responses after 0.5 h (n = 7), 1 h (n = 8), and 2 h (n = 5) of ischemia, respectively (P < 0.001). This avascular, blood-brain barrier-free preparation provides an opportunity to use both metabolic and functional criteria to test protection against neuronal ischemia.

Encephalitis induced by bovine herpesvirus 5 and protection by prior vaccination or infection with bovine herpesvirus 1.

Calves were intranasally challenged with bovine herpesvirus 5 (BHV5) and followed for the development of viral infection, clinical encephalitis, histologic lesions in the brain, and viral sequences in the trigeminal ganglia. Calves that were previously vaccinated with bovine herepesvirus 1 (BHV1, n = 4) or previously infected with BHV1 (n = 5) or that had not been exposed to either virus (n = 4) were compared. No calf developed signs of encephalitis, although all calves developed an infection as indicated by nasal secretion of BHV5 and seroconversion to the virus. Histologic lesions of encephalitis consisting of multifocal gliosis and perivascular cuffs of lymphocytes were observed in calves not previously exposed to BHV1. BHV5 sequences were amplified from the trigeminal ganglia of calves previously vaccinated and from calves not previously exposed to BHV1; calves sequentially challenged with BHV1 and later BHV5 had exclusively BHV1 sequences in their trigeminal ganglia. Administration of dexamethasone 28 days after BHV5 challenge did not influence clinical disease or histologic lesions in either previously unexposed calves (n = 2) or previously immunized calves (n = 2), although it did cause recrudescence of BHV5, as detected by nasal virus secretion.

(R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate.

A diet supplemented with (R)-lipoic acid, a mitochondrial coenzyme, was fed to old rats to determine its efficacy in reversing the decline in metabolism seen with age. Young (3 to 5 months) and old (24 to 26 months) rats were fed an AIN-93M diet with or without (R)-lipoic acid (0.5% w/w) for 2 wk, killed, and their liver parenchymal cells were isolated. Hepatocytes from untreated old rats vs. young controls had significantly lower oxygen consumption (P<0. 03) and mitochondrial membrane potential. (R)-Lipoic acid supplementation reversed the age-related decline in O2 consumption and increased (P<0.03) mitochondrial membrane potential. Ambulatory activity, a measure of general metabolic activity, was almost threefold lower in untreated old rats vs. controls, but this decline was reversed (P<0.005) in old rats fed (R)-lipoic acid. The increase of oxidants with age, as measured by the fluorescence produced on oxidizing 2',7'-dichlorofluorescin, was significantly lowered in (R)-lipoic acid supplemented old rats (P<0.01). Malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were increased fivefold with age in cells from unsupplemented rats. Feeding rats the (R)-lipoic acid diet reduced MDA levels markedly (P<0.01). Both glutathione and ascorbic acid levels declined in hepatocytes with age, but their loss was completely reversed with (R)-lipoic acid supplementation. Thus, (R)-lipoic acid supplementation improves indices of metabolic activity as well as lowers oxidative stress and damage evident in aging.

Outcomes of high-dose unilateral kidney irradiation in patients with gastric lymphoma.

PURPOSE: To review the long-term clinical effects of unilateral kidney irradiation on overall renal function and blood pressure in patients with gastric lymphoma. METHODS AND MATERIALS: In the study were 27 patients with Stage I or II gastric lymphoma who had undergone irradiation of at least 24 Gy to > or = 1/3 of the left kidney. They include 16 women and 11 men, aged 31 to 77, with a mean age of 57.6 years (median 56). Fifteen patients had Stage I and 12 had Stage II disease. In 13 patients the whole kidney had been irradiated, and 14 had had partial kidney irradiation, at doses ranging between 24 and 40.5 Gy. All patients received combined chemotherapy with various drugs: all patients received corticosteroids, and five received cis-platinum. Their follow-up ranged between 0.7 and 7.8 years (mean 3.4 years). Data on possible effects of the treatment on blood pressure, renal function as assessed by blood urea and creatinine, and kidney shrinkage as seen by serial computed tomography scanning were collected on all patients. RESULTS: Three patients had persistent, mild elevations of urea and creatinine levels, which did not require special treatment. All three also received cis-platinum. Ipsilateral kidney shrinkage was evident in most patients. In 19 patients the craniocaudal measurement of the kidney shrank by > or = 1.6 cm. Shrinkage in other dimensions was also evident. The degree of atrophy was related to the volume of kidney irradiated. Only two patients developed hypertension, both at a low level of 150/90; one patient had had 40 Gy to the whole kidney, the other 40 Gy to half the kidney. Neither patient had elevated urea or creatinine. CONCLUSIONS: Notwithstanding the shrinkage to the irradiated part of the kidney, the treatment did not lead to clinically significant hypertension or renal dysfunction. The administration of cis-platinum to patients with gastric lymphoma that requires kidney irradiation should be further evaluated.

Induced hypertension improves regional blood flow and protects against infarction during focal ischemia: time course of changes in blood flow measured by laser Doppler imaging.

OBJECTIVE: To characterize changes in regional blood flow (rCBF) during and after a period of arterial occlusion and determine the effect on rCBF and on the extent of infarction when the mean arterial blood pressure is increased during the period of occlusion. METHODS: rCBF in the middle cerebral artery (MCA) territory of rabbits was monitored using laser Doppler perfusion imaging before, during, and after a 1- or 2-hour period of MCA occlusion, and the size of the infarction was assessed by 2,3,5-triphenyltetrazolamine chloride staining after 2 hours of reperfusion. Test animals, the mean arterial blood pressure of which was increased by 65 mm Hg with intravenous phenylephrine during the ischemia, were compared with control animals that remained normotensive. The laser Doppler perfusion imager (Lisca Developments Co., Linköping, Sweden) scanned a 3-cm2 area of cortex with a resolution of 4 mm2 every 15 minutes. RESULTS: MCA occlusion reduced rCBF to 71 +/- 2% of the control level (n = 24, P < 0.001). Hypertension (HTN) restored rCBF to 84 +/- 3% of the control level (n = 12, P < 0.01), but the HTN-induced improvement diminished with time, so that after 1 hour, there was no longer a significant difference between hypertensive and normotensive animals. HTN during the MCA occlusion caused a 97% reduction in infarct size (P < 0.05) in the animals subjected to 1 hour of occlusion but caused only a 45% reduction (P approximately 0.1) in the animals subjected to 2 hours of occlusion. CONCLUSION: This study supports the use of HTN to minimize ischemic injury from short intervals of major intracranial vessel occlusion but fails to demonstrate protection when HTN is maintained during occlusions of more than 1 hour.

Work transitions.

The healthcare environment is changing rapidly. Work reorganization and redesign can lead to department and unit closures, resulting in work transitions for many staff members. The authors describe the findings of focus groups held with staff and management on units that have closed. These interviews highlight the difficulties encountered with change and provide suggestions to reduce uncertainty during department or unit closures.

Avoiding stroke during cerebral arterial occlusion by temporarily blocking neuronal functions in the rabbit.

The temporary occlusion of cerebral vessels is being used with increased frequency in the surgical management of cerebral vascular disease, and this procedure places brain tissue at risk of infarction. Using a modified version of a well-established model of focal cerebral ischemia in the rabbit, we tested the protective effect of a combination of six agents; each agent was selected to temporarily block one or more neuronal functions, hence reducing their metabolic demands. The combination of six agents had been previously shown to protect neurological function against ischemia. Ten male adult New Zealand White rabbits were anesthetized with halothane, and physiological parameters were maintained within normal ranges. A branch of the left external carotid artery was catheterized and the vasculature supplying the left middle cerebral artery (MCA) territory was isolated. Mannitol was infused via the external carotid artery into the left internal carotid artery to open the blood-brain barrier in the territory of the MCA. This infusion was followed by either Ames' medium alone (control) or Ames' medium containing the combination of agents: tetrodotoxin (0.1 micromol/L), 2-amino-4-phosphonobutyric acid (20 mumol/L), 2-amino-5-phosphonovaleric acid (1 mmol/L), amiloride (1 mmol/L), magnesium (10 mmol/L), and lithium (10 mmol/L). Ischemia in the left MCA territory was then induced for 2 hours, followed by 4 hours of reperfusion. Animals pretreated with the combination of agents sustained infarctions that were markedly smaller (mean+/-SEM, 46+/-19.7 mm(3), n=5) than control animals (300+/-46.5 mm(3), n=5, P<.001). We conclude that the strategy of locally delivering a combination of agents designed to temporarily reduce neuronal metabolic demands by temporarily blocking several nonvital neuronal functions, can reduce the infarction induced by a focal reduction in cerebral blood flow in the rabbit.