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.

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.

A simple freeze-fracture replication method for electron microscopy.

A simple method to achieve results similar to the freeze-etching technique of Moor et al. (1961) is described. The frozen tissue is cut under liquid nitrogen with a razor blade outside the evaporator rather than inside with a cooled microtome. The conditions of the experiment do not favor sublimation, and it is proposed that the structure of the replica be explained by local faults in the cleavage plane which leaves structures, such as membranes, standing above the ice. Micrographs of replicas of glycerol-protected frozen small intestine of mouse prepared by the method are presented and the structural details they show are discussed. The problem of vapor-deposited contamination is discussed. It is concluded that this is a practical method for obtaining electron micrographs that are relatively free of artifact, and that further improvements may be expected from the use of rapidly frozen fresh tissue and a clean vacuum system, possibly of the ion-pumped type.

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.

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.

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.

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.

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.

Protection against CNS ischemia by temporary interruption of function-related processes of neurons.

Previous studies have shown that most of the energy consumption of CNS tissue is used for processes that subserve signaling functions of the cells. Since these function-related processes are probably not essential to cell viability, blocking them reversibly with a combination of pharmacologic agents should protect cells from a reduction in energy metabolism. Preliminary experiments to test this hypothesis were performed on isolated rabbit retinas. They were maintained in a newly devised chamber that permitted continuous monitoring of electrophysiological function for > or = 8 h. Ischemia was simulated by a 6-fold reduction in both O2 and glucose. This caused a rapid (t1/2 75 s) and complete loss of the light-evoked response in the optic nerve. Untreated retinas showed full recovery after 1/2 h of deprivation, but only 50% recovery after 1 h and little or no recovery after 2 or 3 h. Retinas exposed during 3 h of deprivation to a combination of six agents that abolished electrophysiologic function and reduced glucose utilization [tetrodotoxin (TTX), 2-amino-4-phosphonobutyric acid (APB), 2-amino-5-phosphonovaleric acid (APV), amiloride, Mg2+, and Li+] showed full recovery. We conclude that reducing energy requirements by blocking functional processes can prevent ischemic damage.

Retina subjected to components of ischemia in vitro. Selective vulnerability and minimum lethal exposure of neurons and glia to oxygen and/or glucose deprivation and to loss of exchange with incubating medium.

Rabbit retinas were incubated at 37 C in media lacking oxygen, glucose, or both, or sealed in a small compartment without medium to convert them to a "closed system." They were then returned to control medium before being fixed for microscopy. Other retinas were incubated only in control medium and then fixed. Conversion of the retina to a closed system caused irreversible damage to all cell types within 40 minutes. Combined deprivation of oxygen and glucose also irreversibly damaged the neuronal cells within 40 minutes, but Mueller cells,the principal glial cells of the retina, were not irreversibly altered by 90 minutes of the deprivation. Deprivation of oxygen alone caused irreversible damage to receptor cells in 80 minutes, but the cells of the inner nuclear layer, ganglion cells, and Mueller cells retained normal structure for at least 180 minutes. Deprivation of glucose alone damaged receptor cells in 160 minutes and the other neuronal cells in 180 minutes, but did not irreversibly damage Mueller cells by 200 minutes.

Cell volume and permeability of oxygen-and glucose-deprived retina in vitro.

Rabbit retina was deprived of O(2) and glucose in vitro for up to four hours at 37 C. Intracellular volume was measured, using inulin as an extracellular marker. After a 30-minute latency, cells swelled rapidly to more than twice normal volume while extracellular volume was unchanged. Intracellular accumulation of water was not reversed by resupply of oxygen and glucose. Permeability to small molecules was assessed with mannitol. The ratio of mannitol space to inulin space averaged 1.0 in controls. This ratio remained 1.0 up to 30 minutes of deprivation, but increased to 1.2 by 60 minutes. Permeability to large molecules was assessed from the rate of loss of isotopically labeled cell protein into the medium. There was no difference between control and deprived retinas up to three hours.

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.

Synthesis and breakdown of different sized retinal proteins in darkness and during photic stimulation.

Rabbit retinas were maintained in vitro in medium resembling cerebrospinal fluid and were exposed to (3)H-leucine or (14)C-leucine in double-labeling experiments designed to measure rates of protein turnover and to determine the effects of photic stimulation on protein synthesis and degradation. The retinas were solubilized, and the proteins separated according to size by polyacrylamide gel electrophoresis. The gels were cut into 95 slices and each slice differentially counted. Protein content of the slices was estimated from Coomassie Blue staining, and molecular weight (MW) from distribution along the gel of MW standards. The retinas appeared to function nearly normally in vitro for many hours. Protein renewal was rapid and reproducible at 0.55 +/- 0.01 (S.E.M.) %/h and remained quite constant for at least 7 h. Synthesis and degradation were approximately equal. Two retinas were maintained in vitro at 37 degrees C for 52 h, and showed good preservation of morphology, electrophysiological response to light, and protein synthesis. Total synthesis of new polypeptides was at the rate of 103 nmole per g of protein, per h; there was a sharp peak in the 33,000 to 43,000 MW range. Proteins in every size group were very heterogeneous with respect to breakdown coefficients (i.e. longevity) which were the prime determinants of the amount of each protein present. Fractional renewal showed a highly significance (p<0.0001) correlation with MW, due apparently to a reduction in maximal longevity as size increased. Neither synthesis nor degradation was significantly affected by intense continuous light or flashing light, though the latter increased uptake of 2-deoxyglucose by 38%.

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.

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.

Steady state feedback in mammalian phototransduction illustrated by a nomogram.

Published data characterizing the four reactions responsible for the Ca(2+)-mediated negative feedback in mammalian rod phototransduction were used to generate graphs which are combined in a circular fashion so that the y-axis of one serves as the x-axis of the next. The nomogram thus created makes it possible to determine by inspection the steady state situation in darkness, and the quasi-steady state situations that pertain shortly after exposure to light of different intensities. The results predicted by the nomogram suggest that Ca(2+)-mediated negative feedback is responsible for the Weber-Fechner relationship between stimulus and response.

Reduction of cellular energy requirements. Screening for agents that may protect against CNS ischemia.

Protection of the brain and spinal cord against ischemia is a goal of vast clinical importance. One approach to this objective is to reduce the tissue's functional activity in order to preserve energy for the metabolic processes that are essential to viability. Experiments to explore ways of reducing function-related energy demands were performed on isolated rabbit retina, a well-characterized model of organized adult mammalian central nervous system (CNS) tissue. The retina was maintained in a nearly physiological state in a miniature "heart-lung" apparatus. Energy metabolism (oxygen consumption and glycolysis) and electrophysiological function (determined by electroretinogram) of the in vitro retina were monitored, and their responses to a series of agents that may reduce energy requirements were determined. Large reversible reductions in O2 consumption, glycolysis, and electrophysiological function were seen in response to mild hypothermia (-3 degrees to -6 degrees C), phenytoin (Dilantin, 100 to 200 mg/kg), chlordiazepoxide (Librium, 200 microM), lithium (1 to 4 mM), Mg++ (6 to 20 mM), strophanthidin (0.15 to 0.25 microM), CO2 (25% to 30%), 2-amino-5-phosphonovaleric acid (APV, 500 microM), amiloride (1 mM), and dantrolene (1 mM). One retina was exposed simultaneously to a combination of six of these agents, which reduced its oxidative and glycolytic metabolism to less than 50% of the control level. The retina recovered metabolic and electrophysiological function after a 2 1/2-hour exposure period. Other agents tested (diphenhydramine, midazolam, nifedipine, nimodipine, and quercetin) had effects on energy metabolism and electrophysiological function that were poorly reversible. Surprisingly little effect was seen in response to general anesthetic agents (thiopental and Althesin) and other CNS depressants (chlorpromazine, ethanol, lidocaine, paraldehyde, valproic acid, and baclofen). The presumed mechanisms through which these agents reduce cellular energy requirements, as well as their potential roles in the treatment of CNS ischemia, are discussed.

Prevalence of personality disorders in community-living elderly.

There has been limited research on the prevalence of personality disorders in the aged. No studies have documented the extent of personality disorders in community-dwelling elderly with the use of a structured scale specifically designed to detect personality disorders and anchored to DSM-III-R criteria. One hundred male and 100 female community-living elderly (mean age, 72.1 years) were administered the Structured Interview for Disorders of Personality-Revised to compare prevalence rates for specific personality disorders with those of young adults (mean age, 41.7 years) and to identify demographic variables associated with personality disorders in the elderly. Results indicate a tendency toward fewer personality disorders in older than young adults, no differences in the frequency of personality disorders between male and female elderly, and significantly more prior mental health consultations in elderly with personality disorders than in elderly without these disorders. Aging processes and methodologic issues that could account for differences in personality disorder distribution between young and older adults are discussed. Recommendations for future research are outlined.

Prevalence of personality disorders in two geropsychiatric inpatient units.

One hundred males from a Veterans Affairs geropsychiatric inpatient ward, and 100 females from a geropsychiatric inpatient ward of a private hospital completed the Structured Interview for Disorders of Personality-Revised (SIDP-R). Chart reviews provided information including age, years of education, marital status, race, as well as Axis I and Axis II psychiatric diagnoses. Data from a young adult sample, drawn from an initial SIDP-R validation study, were used for comparison. Results indicate a 56.5% rate of personality disorders (PD) for older patients. Significantly more elderly men than elderly women were diagnosed with PD by psychiatric evaluation, and elderly men were also more likely to be diagnosed with paranoid, avoidant, and multiple PD using the SIDP-R. Psychiatrists gave far fewer Axis II diagnoses than were yielded by the SIDP-R, particularly with females. There were no significant differences in total PD rates between aged and young subjects, but older adults with PD were diagnosed less frequently with multiple PD. Older adults were also less likely to be diagnosed with the "Dramatic" cluster PD, and more likely to be diagnosed with the "Odd" cluster PD. The level of depression was related to both clinical and SIDP-R diagnoses.

An appraisal of the "Vacutainer" system for blood collection.

The conventional syringe/needle/container system for the collection and handling of blood samples is compared with the Vacutainer system using evacuated tubes. The relative advantages and disadvantages of both systems are evaluated. The Vacutainer system is quicker and simpler to use, with greater versatility, producing blood specimens of higher quality and at a cost comparable with that by the syringe system. The problems of blood contamination during blood sampling and distribution with both systems are discussed.