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Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). Our aim was to study the prophylactic effect of high-dose intravenous acyclovir given around the time of BMT followed by oral acyclovir on CMV infection and survival. 310 BMT recipients at risk of developing CMV infection were randomised to one of three regimens in a double-blind and double-dummy design: intravenous acylclovir (500 mg/m2, three times a day) for 1 month followed by oral acyclovir (800 mg four times a day for a further 6 months) (intravenous/oral group); intravenous acyclovir followed by oral placebo (intermediate group); or low-dose oral acyclovir (200 or 400 mg, four times a day) followed by placebo ("controls"). Analysis was by intention-to-treat. Intravenous acyclovir significantly reduced the probability of and delayed the onset of CMV infection. There was no further reduction in infection risk with the addition of long-term oral acyclovir. Time to CMV viraemia was delayed in the intravenous/oral acyclovir group compared with controls. Extending the prophylaxis with oral acyclovir significantly improved survival: 79 of 105 recipients were still alive at 7 months compared with 60 of 102 controls (p = 0.012). Although the intravenous/oral acyclovir group did significantly better than controls in terms of survival, the difference between the intravenous/oral acyclovir group and the intermediate group was of borderline statistical significance (p = 0.054). Adverse events that were possibly treatment related were similar in all three groups. The most commonly reported events were nausea, vomiting, elevated creatinine, and renal failure. High-dose intravenous followed by oral acyclovir improved survival and was of benefit in prophylaxis against the effects of CMV after BMT. Interpretation of CMV infection was made difficult because an intermediate treatment (intravenous acyclovir followed by oral placebo) was as effective as high-dose intravenous/oral acyclovir. [ABSTRACT FROM AUTHOR]

With less than half of the world's urban population having safely managed sanitation due to the high cost and difficulty of building sewers and treatment plants, many rely on off-grid options like pit latrines and septic tanks, which are hard to empty and often lead to illegal waste dumping; this research focuses on container-based sanitation (CBS) as an emerging off-grid solution. Off-grid sanitation refers to waste management systems that operate independently of centralized infrastructure and CBS is a service providing toilets that collect human waste in sealable containers, which are regularly emptied and safely disposed of. These data relate to a project investigating CBS in Kenya, Peru, and South Africa, focusing on how different user groups access and utilize sanitation - contrasting CBS with other types. Participants, acting as citizen scientists, collected confidential data through a dedicated smartphone app designed by the authors and external contractors. This project aimed to explore the effective scaling, management, and regulation of off-grid sanitation systems, relevant to academics in urban planning, water and sanitation services, institutional capability, policy and governance, and those addressing inequality and poverty reduction. The 12-month data collection period offered participants small incentives for weekly engagement, in a micro payment for micro tasks approach. Participants were randomly selected, attended a training workshop, and (where needed) were given a smartphone which they could keep at the end of the project. We conducted weekly smartphone surveys in over 300 households across informal settlements. These surveys aimed to understand human-environment interactions by capturing daily life, wellbeing, income, infrastructural service use, and socioeconomic variables at a weekly resolution, contributing to more informed analyses and decision-making. The smartphone-based approach offers efficient, cost-effective, and flexible data collection, enabling extensive geographical coverage, broad subject areas, and frequent engagement. The Open Data Kit (ODK) tools were used to support data collection in the resource-constrained environment with limited or intermittent connectivity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Diastase is used internationally as a quality monitor for excessive heat treatment and prolonged storage of honey; honey must contain an activity of at least 8 diastase numbers (DN) for it to be considered export quality. Freshly harvested mānuka honey can have diastase activity close to the export threshold of 8 DN without excess heating, increasing susceptibility for export failure. This research investigated the effect of compounds unique to or high in concentration in mānuka honey on diastase activity. Investigation of the effect of methylglyoxal, dihydroxyacetone, 2-methoxybenzoic acid, 3-phenyllatic acid, 4-hydroxyphenyllactic acid and 2'-methoxyacetophenone on diastase activity was carried out. Mānuka honey was stored at 20 and 27 °C and clover honey spiked with compounds of interest were stored at 20, 27 and 34 °C and monitored overtime. Methylglyoxal and 3-phenyllactic acid were found to accelerate the loss of diastase above the loss normally observed with time and elevated temperature., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This paper explores the link between personal experience with COVID-19 and US retail investors' financial decision-making during the first COVID-19 wave. Do retail investors that have personally experienced COVID-19 change their investments after the pandemic outbreak, and if so, why? We use a cross-sectional dataset from an online survey of US retail investors collected in July and August 2020 to assess if and how respondents change their investment decisions after the COVID-19 outbreak. On average retail investors increase their investments during the first wave of COVID-19 by 4.7%, while many of them decrease their investments suggesting a high heterogeneity of investor behaviours. We provide the first evidence that personal experience with the virus can have unexpected positive effects on retail investments. Investors who have personal experience with COVID-19, who are in a vulnerable health category, who tested positive, and who know someone in their close circle of friends or family who died because of COVID-19, increase their investments by 12%. We explain our findings through terror management theory, salience theory and optimism bias, suggesting that reminders of mortality, focussing on selective salient investment information, and over-optimism despite personal vulnerable health contribute to the increase in retail investments. Increased levels of savings, saving goals and risk capacity are also positively associated with increased investments. Our findings are relevant to investors, regulators, and financial advisors, and highlight the importance of providing retail investors with access to investment opportunities in periods of unprecedented shocks such as COVID-19., (© 2023 The Authors. Published by Elsevier Inc.)

In conventional gases and plasmas, it is known that heat fluxes are proportional to temperature gradients, with collisions between particles mediating energy flow from hotter to colder regions and the coefficient of thermal conduction given by Spitzer's theory. However, this theory breaks down in magnetized, turbulent, weakly collisional plasmas, although modifications are difficult to predict from first principles due to the complex, multiscale nature of the problem. Understanding heat transport is important in astrophysical plasmas such as those in galaxy clusters, where observed temperature profiles are explicable only in the presence of a strong suppression of heat conduction compared to Spitzer's theory. To address this problem, we have created a replica of such a system in a laser laboratory experiment. Our data show a reduction of heat transport by two orders of magnitude or more, leading to large temperature variations on small spatial scales (as is seen in cluster plasmas).

Sexuality has become an area of social competence in which individuals strive to be recognized as sexually competent performers. However, a large proportion of young women experience reduced sexual desire. In this study, both quantitative and qualitative methods were applied. Using data from a questionnaire, the aim of this study was to explore the prevalence of, and the factors associated with, lack of sexual interest and desire among young women in Norway. Further, with the help of in-depth interviews, we investigated how young women with reduced sexual desire experience living with their desire problems and what they experience as the cause of their problems. The sample in the quantitative study consisted of 505 Norwegian women between the ages of 18 and 29 years. ANOVA was employed to explore differences in scores on psychological factors and relational factors, as well as between participants who experienced a lack of sexual interest and desire, and those who did not. The results indicate a high prevalence of lack of sexual interest and desire among women (37.1%), while low appearance satisfaction and low relationship satisfaction were central predictors of lack of sexual interest and desire. The sample in the qualitative study consisted of ten Norwegian women with reduced sexual desire between the ages of 18 and 29 years. Through thematic analysis, four themes emerged as experiences of living with reduced sexual desire: (1) physical and mental health, (2) being a young woman in today's society, (3) relational factors, (4) negative experiences, personal expectations toward sexuality, and sexual trauma., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial interests to disclose., (© The Author(s) 2022.)

Understanding magnetic-field generation and amplification in turbulent plasma is essential to account for observations of magnetic fields in the universe. A theoretical framework attributing the origin and sustainment of these fields to the so-called fluctuation dynamo was recently validated by experiments on laser facilities in low-magnetic-Prandtl-number plasmas ([Formula: see text]). However, the same framework proposes that the fluctuation dynamo should operate differently when [Formula: see text], the regime relevant to many astrophysical environments such as the intracluster medium of galaxy clusters. This paper reports an experiment that creates a laboratory [Formula: see text] plasma dynamo. We provide a time-resolved characterization of the plasma's evolution, measuring temperatures, densities, flow velocities, and magnetic fields, which allows us to explore various stages of the fluctuation dynamo's operation on seed magnetic fields generated by the action of the Biermann-battery mechanism during the initial drive-laser target interaction. The magnetic energy in structures with characteristic scales close to the driving scale of the stochastic motions is found to increase by almost three orders of magnitude and saturate dynamically. It is shown that the initial growth of these fields occurs at a much greater rate than the turnover rate of the driving-scale stochastic motions. Our results point to the possibility that plasma turbulence produced by strong shear can generate fields more efficiently at the driving scale than anticipated by idealized magnetohydrodynamics (MHD) simulations of the nonhelical fluctuation dynamo; this finding could help explain the large-scale fields inferred from observations of astrophysical systems., Competing Interests: Competing interest statement: The authors declare a competing interest (as defined by PNAS policy). A.F.A.B., M.W.K., and N.A.B. are affiliated with Princeton University. They have not collaborated. The authors declare that they have no other conflicts of interest.

To date, projections of human migration induced by sea-level change (SLC) largely suggest large-scale displacement away from vulnerable coastlines. However, results from our model of Bangladesh suggest counterintuitively that people will continue to migrate toward the vulnerable coastline irrespective of the flooding amplified by future SLC under all emissions scenarios until the end of this century. We developed an empirically calibrated agent-based model of household migration decision-making that captures the multi-faceted push, pull and mooring influences on migration at a household scale. We then exposed ~4800 000 simulated migrants to 871 scenarios of projected 21st-century coastal flooding under future emissions pathways. Our model does not predict flooding impacts great enough to drive populations away from coastlines in any of the scenarios. One reason is that while flooding does accelerate a transition from agricultural to non-agricultural income opportunities, livelihood alternatives are most abundant in coastal cities. At the same time, some coastal populations are unable to migrate, as flood losses accumulate and reduce the set of livelihood alternatives (so-called 'trapped' populations). However, even when we increased access to credit, a commonly-proposed policy lever for incentivizing migration in the face of climate risk, we found that the number of immobile agents actually rose. These findings imply that instead of a straightforward relationship between displacement and migration, projections need to consider the multiple constraints on, and preferences for, mobility. Our model demonstrates that decision-makers seeking to affect migration outcomes around SLC would do well to consider individual-level adaptive behaviors and motivations that evolve through time, as well as the potential for unintended behavioral responses., Competing Interests: Conflict of interest The authors declare no competing interests.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 10 13 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.

High-frequency social data collection may facilitate improved recall, more inclusive reporting, and improved capture of intra-period variability. Although there are examples of small studies collecting particular variables at high frequency in the social science literature, to date there have been no significant efforts to collect a wide range of variables with high frequency. We have implemented the first such effort with a smartphone-based data collection approach, systematically varying the frequency of survey task and recall period, allowing the analysis of the relative merit of high-frequency data collection for different key variables in household surveys. This study of 480 farmers from northwestern Bangladesh over approximately one year of continuous data on key measures of household and community wellbeing could be particularly useful for the design and evaluation of development interventions and policies. While the data discussed here provide a snapshot of what is possible, we also highlight their strength for providing opportunities for interdisciplinary research in the household agricultural production, practices, seasonal hunger, etc., in a low-income agrarian society.

The properties of supersonic, compressible plasma turbulence determine the behavior of many terrestrial and astrophysical systems. In the interstellar medium and molecular clouds, compressible turbulence plays a vital role in star formation and the evolution of our galaxy. Observations of the density and velocity power spectra in the Orion B and Perseus molecular clouds show large deviations from those predicted for incompressible turbulence. Hydrodynamic simulations attribute this to the high Mach number in the interstellar medium (ISM), although the exact details of this dependence are not well understood. Here we investigate experimentally the statistical behavior of boundary-free supersonic turbulence created by the collision of two laser-driven high-velocity turbulent plasma jets. The Mach number dependence of the slopes of the density and velocity power spectra agree with astrophysical observations, and supports the notion that the turbulence transitions from being Kolmogorov-like at low Mach number to being more Burgers-like at higher Mach numbers.

Conservation agriculture (CA) is a management paradigm in which soil is covered outside of cropping seasons, minimally disturbed, and recharged with nitrogen-fixing legumes. Finding effective ways to encourage CA is a centuries-old problem playing out acutely today in Sub-Saharan Africa. To better understand this issue, we have collected data on rural livelihoods and CA adoption during a two-year intervention in southern Malawi. The intervention evaluated rates of CA adoption under two different structures of payment and three levels of monitoring. The dataset includes a baseline and endline survey covering 1,900 households, along with surveys conducted with participants opting into the intervention. Baseline and endline questions included modules on farm-level inputs and production at the plot-crop level; plot characteristics; household composition and assets; savings, loans, and other sources of income; neighborhood characteristics; and perceptions regarding CA. Registration questionnaires in the intervention included detailed assessments of recent production in plots being registered to the intervention, and basic information for all other plots; and basic information on household structure and assets.

Magnetic fields are ubiquitous in the Universe. The energy density of these fields is typically comparable to the energy density of the fluid motions of the plasma in which they are embedded, making magnetic fields essential players in the dynamics of the luminous matter. The standard theoretical model for the origin of these strong magnetic fields is through the amplification of tiny seed fields via turbulent dynamo to the level consistent with current observations. However, experimental demonstration of the turbulent dynamo mechanism has remained elusive, since it requires plasma conditions that are extremely hard to re-create in terrestrial laboratories. Here we demonstrate, using laser-produced colliding plasma flows, that turbulence is indeed capable of rapidly amplifying seed fields to near equipartition with the turbulent fluid motions. These results support the notion that turbulent dynamo is a viable mechanism responsible for the observed present-day magnetization.

The advent of cheap smartphones in rural areas across the globe presents an opportunity to change the mode with which researchers engage hard-to-reach populations. In particular, smartphones allow researchers to connect with respondents more frequently than standard household surveys, opening a new window into important short-term variability in key measures of household and community wellbeing. In this paper, we present early results from a pilot study in rural Bangladesh using a 'microtasks for micropayments' model to collect a range of community and household living standards data using Android smartphones. We find that more frequent task repetition with shorter recall periods leads to more inclusive reporting, improved capture of intra-seasonal variability, and earlier signals of events such as illness. Payments in the form of mobile talk time and data provide a positive development externality in the form of expanded access to mobile internet and social networks. Taken to scale, programs such as this have potential to transform data collection in rural areas, providing near-real-time windows into the development of markets, the spread of illnesses, or the diffusion of ideas and innovations., Competing Interests: We have the following interests: Development of the software interface was undertaken by Nafundi. Implementation in the field was facilitated by Banglalink and by WIN Incorporated. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLoS ONE policies on sharing data and materials.

It is widely argued that farmers are unwilling to pay adequate fees for surface water irrigation to recover the costs associated with maintenance and improvement of delivery systems. In this paper, we use a discrete choice experiment to study farmer preferences for irrigation characteristics along two branch canals in Punjab Province in eastern Pakistan. We find that farmers are generally willing to pay well in excess of current surface water irrigation costs for increased surface water reliability and that the amount that farmers are willing to pay is an increasing function of their existing surface water supply as well as location along the main canal branch. This explicit translation of implicit willingness-to-pay (WTP) for water (via expenditure on groundwater pumping) to WTP for reliable surface water demonstrates the potential for greatly enhanced cost recovery in the Indus Basin Irrigation System via appropriate setting of water user fees, driven by the higher WTP of those currently receiving reliable supplies.

It is possible using current high-intensity laser facilities to reach the quantum radiation reaction regime for energetic electrons. An experiment using a wakefield accelerator to drive GeV electrons into a counterpropagating laser pulse would demonstrate the increase in the yield of high-energy photons caused by the stochastic nature of quantum synchrotron emission: we show that a beam of 10(9) 1 GeV electrons colliding with a 30 fs laser pulse of intensity 10(22)  W cm(-2) will emit 6300 photons with energy greater than 700 MeV, 60× the number predicted by classical theory.

A novel absorption mechanism for linearly polarized lasers propagating in relativistically underdense solids in the ultrarelativistic (a ~ 100) regime is presented. The mechanism is based on strong synchrotron emission from electrons reinjected into the laser by the space charge field they generate at the front of the laser pulse. This laser absorption, termed reinjected electron synchrotron emission, is due to a coupling of conventional plasma physics processes to quantum electrodynamic processes in low density solids at intensities above 10(22) W/cm(2). Reinjected electron synchrotron emission is identified in 2D QED-particle-in-cell simulations and then explained in terms of 1D QED-particle-in-cell simulations and simple analytical theory. It is found that between 1% (at 10(22) W/cm(2)) and 14% (at 8 × 10(23) W/cm(2)) of the laser energy is converted into gamma ray photons, potentially providing an ultraintense future gamma ray source.

In simulations of a 10 PW laser striking a solid, we demonstrate the possibility of producing a pure electron-positron plasma by the same processes as those thought to operate in high-energy astrophysical environments. A maximum positron density of 10(26) m(-3) can be achieved, 7 orders of magnitude greater than achieved in previous experiments. Additionally, 35% of the laser energy is converted to a burst of γ rays of intensity 10(22) W cm(-2), potentially the most intense γ-ray source available in the laboratory. This absorption results in a strong feedback between both pair and γ-ray production and classical plasma physics in the new "QED-plasma" regime.

The standard model for the origin of galactic magnetic fields is through the amplification of seed fields via dynamo or turbulent processes to the level consistent with present observations. Although other mechanisms may also operate, currents from misaligned pressure and temperature gradients (the Biermann battery process) inevitably accompany the formation of galaxies in the absence of a primordial field. Driven by geometrical asymmetries in shocks associated with the collapse of protogalactic structures, the Biermann battery is believed to generate tiny seed fields to a level of about 10(-21) gauss (refs 7, 8). With the advent of high-power laser systems in the past two decades, a new area of research has opened in which, using simple scaling relations, astrophysical environments can effectively be reproduced in the laboratory. Here we report the results of an experiment that produced seed magnetic fields by the Biermann battery effect. We show that these results can be scaled to the intergalactic medium, where turbulence, acting on timescales of around 700 million years, can amplify the seed fields sufficiently to affect galaxy evolution.

Cardiotoxicity, also referred to as drug-induced cardiac injury, is an issue associated with the use of some small-molecule kinase inhibitors and antibody-based therapies targeting signaling pathways in cancer. Although these drugs have had a major impact on cancer patient survival, data have implicated kinase-targeting agents such as sunitinib, imatinib, trastuzumab, and sorafenib in adversely affecting cardiac function in a subset of treated individuals. In many cases, adverse cardiac events in the clinic were not anticipated based on preclinical safety evaluation of the molecule. In order to support the development of efficacious and safe kinase inhibitors for the treatment of cancer and other indications, new preclinical approaches and screens are required to predict clinical cardiotoxicity. Laboratory investigations into the underlying molecular mechanisms of heart toxicity induced by these molecules have identified potentially common themes including mitochondrial perturbation and modulation of adenosine monophosphate-activated protein kinase activity. Studies characterizing cardiac-specific kinase knockout mouse models have developed our understanding of the homeostatic role of some of these signaling mediators in the heart. Therefore, when considering kinases as potential future targets or when examining secondary pharmacological interactions of novel kinase inhibitors, these models may help to inform us of the potential adverse cardiac effects in the clinic.

In the Amazonian agricultural frontier, pasture for cattle ranching is an important and potentially hazardous form of land use because of sediment erosion as pastures degrade. This relationship between ranching, sediment load, and water quality is likely to further exacerbate environmental impacts, particularly in the context of climate change. We examine the role that river basin councils (RBCs) - a water governance option of Brazil's 1997 National Water Act - might play in managing this nonpoint-source pollution in the Amazônian state of Rondônia. We implement a simple coupled rancher-water system model to compare two potential governance options: a bulk water cleanup charge (BWC) implemented by RBCs and a land-use fine (LUF) for failing to maintain riparian buffers. We find no significant advantage of BWC over LUF in reducing sediment loading while keeping ranching profitable, under a changing climate. We also fail to find in Rondônia the important stake in water issues that has driven water reform elsewhere in Brazil. Moreover, the comparative success of reforestation programs suggests these programs may, in fact, have the potential to manage nonpoint-source agricultural pollution in the region.

Recombinant expression of the aryl hydrocarbon receptor (AhR) yields small amounts of ligand-binding-competent AhR. Therefore, Spodoptera frugiperda (Sf9) cells and baculovirus have been evaluated for high-level and functional expression of AhR. Rat and human AhR were expressed as soluble protein in significant amounts. Expression of ligand-binding-competent AhR was sensitive to the protein concentration of Sf9 extract, and coexpression of the chaperone p23 failed to affect the yield of functional ligand-binding AhR. The expression system yielded high levels of functional protein, with the ligand-binding capacity (Bmax) typically 20-fold higher than that obtained with rat liver cytosol. Quantitative estimates of the ligand-binding affinity of human and rat AhR were obtained; the Kd for recombinant rat AhR was indistinguishable from that of native rat AhR, thereby validating the expression system as a faithful model for native AhR. The human AhR bound TCDD with significantly lower affinity than the rat AhR. These findings demonstrate high-level expression of ligand-binding-competent AhR, and sufficient AhR for quantitative analysis of ligand binding.

Prolific electron-positron pair production is possible at laser intensities approaching 10;{24} W cm;{-2} at a wavelength of 1 mum. An analysis of electron trajectories and interactions at the nodes (B=0) of two counterpropagating, circularly polarized laser beams shows that a cascade of gamma rays and pairs develops. The geometry is generalized qualitatively to linear polarization and laser beams incident on a solid target.

We study how the proton density in a target irradiated by an ultraintense laser affects the proton spectrum, with analytical models and Vlasov simulations. A low relative proton density gives rise to peaks in the energy spectrum. Furthermore, a target with the protons confined to a thin, low density layer produces a quasimonoenergetic spectrum. This is a simple technique for producing proton beams with a narrow energy spread for proton radiography of laser-plasma interactions.

Superheating alcohol solutions of simple trimetallic vanadium(III) precursors gives the octa- and decametallic vanadium(III) clusters [V(8)(OEt)(8)(OH)(4)(O(2)CPh)(12)] (1) and [V(10)(OMe)(20)(O(2)CMe)(10)] (2). Cluster 2 is the largest vanadium(III) cluster synthesised to date. Thus solvothermal synthetic techniques are an excellent route to high-nuclearity vanadium(III) clusters. Both 1 and 2 consist of a planar or near-planar array of V(III) ions. The metal ions in 1 are bridged by either a micro(2)-hydroxide and two micro(2)-benzoate groups or two micro(2)-ethoxides and a micro(2)-benzoate groups, the two bridging arrangements alternating around the ring. In 2 each pair of neighbouring metal ions is bridged by two micro(2)-methoxides and a micro(2)-acetate, and this molecule is the V(III) analogue of Lippard's famous "ferric wheel". Preliminary magnetic susceptibility studies show the exchange coupling in both complexes to be antiferromagnetic in nature, with the coupling stronger in 1 than in 2.

Intense relativistic electron beams, produced by high-intensity short-pulse laser irradiation of a solid target, have many potential applications including fusion by fast ignition. Using a unique Fokker-Planck code, supported by analytic calculations, we show that fast electrons can be collimated into a beam even when the fast electron source is not strongly anisotropic, and we derive a condition for collimation to occur.

1. Interpretation of novel drug exposure and toxicology data from the dog is tempered by our limited molecular and functional knowledge of dog cytochromes P450 (CYPs). The aim was to study the mRNA and protein expression of hepatic dog CYPs in relation to the metabolism of substrates of human CYP, particularly those of the CYP2C subfamily. 2. The rate of 7-hydroxylation of S-warfarin (CYP2C9 in humans) by dog liver microsomes (mean +/- SD from 12 (six male and six female) dogs = 10.8 +/- 1.9 fmol mg(-1) protein min(-1)) was 1.5-2 orders of magnitude lower than that in humans. 3. The rate of 4'-hydroxylation of S-mephenytoin, catalysed in humans by CYP2C19, was also low in dog liver (4.6 +/-1.5 pmol mg(-1) protein min(-1)) compared with human liver. In contrast, the rate of 4'-hydroxylation of the R-enantiomer of mephenytoin by dog liver was much higher. The kinetics of this reaction (range of K(m) or K(0.5) 15-22 micro M, V(max) 35-59 pmol mg(-1) protein min(-1), n = 4 livers) were consistent with the involvement of a single enzyme. 4. In contrast to our findings for S-mephenytoin, dog liver microsomes 5'-hydroxylated omeprazole (also catalysed by CYP2C19 in humans) at considerably higher rates (range of K(m) 42-64 micro M, V(max) 22-46 pmol mg(-1) protein min(-1), n = 4 livers). 5. For all the substrates except omeprazole, a sex difference in their metabolism was observed in the dog (dextromethorphan N-demethylation: female range = 0.7-0.9, male = 0.4-0.8 nmol mg(-1) protein min(-1) (p < 0.02); S-warfarin 7-hydroxylation: female = 9-15.5, male = 8-12 fmol mg(-1) protein min(-1) (p < 0.02); R-mephenytoin 4'-hydroxylation: female = 16-35, male = 11.5-19 pmol mg(-1) protein min(-1) (p < 0.01); omeprazole 5'-hydroxylation: female = 15-20, male 13-22 pmol mg(-1) protein min(-1) (p < 0.2)). 6. All dog livers expressed mRNA and CYP3A12, CYP2B11, CYP2C21 proteins, with no sex differences being found. Expression of CYP2C41 mRNA was undetectable in the livers of six of 11 dogs. 7. Correlation analysis suggested that CYP2B11 catalyses the N-demethylation of dextromethorphan (mediated in humans by CYP3A) and the 4'-hydroxylation of mephenytoin (mediated in humans by CYP2C19) in the dog, and that this enzyme and CYP3A12 contribute to S-warfarin 7-hydroxylation (mediated in humans by CYP2C9). 8. In conclusion, we have identified a distinct pattern of hepatic expression of the CYP2C41 gene in the Alderley Park beagle dog. Furthermore, marked differences in the metabolism of human CYP2C substrates were observed in this dog strain compared with humans with respect to rate of reaction, stereoselectivity and CYP enzyme selectivity.

Conventional theories of magnetic-field generation by laser pulses in collisional plasmas require the presence of density gradients or anisotropic pressure. Using the first two-dimensional Fokker-Planck code to self-consistently include magnetic fields, we find that magnetic fields can be spontaneously generated when a collisional plasma is nonuniformly heated even though inverted delta n = 0 and the pressure is purely isotropic. These magnetic fields, which can become strong enough to significantly affect transport, are attributed to nonlocal effects that are missing in the standard, local theories.

Plasma formation in metallic wire Z pinches is modeled using a two-dimensional resistive magnetohydrodynamics code. Modified Thomas-Fermi equations of state and dense plasma transport coefficients allow the phase transitions from solid to plasma to be approximated. Results indicate the persistence of a two-component structure with a cold, dense core embedded within a much hotter, low density, m=0 unstable corona. Extensive benchmark testing against data from a number of single-wire experiments is presented. Artificial laser schlieren and x-ray back-lighting images generated from the code data are compared directly to experimental results. The results were found to be insensitive to inaccuracies in the equations of state and transport coefficients. Simulations of individual wires in a wire array show different behavior to that observed experimentally due to the absence of three-dimensional effects. Simulations with similar conditions to wires in an array show a general trend in the plasma structure at start of implosion from discrete wires with large m=0 perturbation amplitudes to partially merged wires with smaller perturbation amplitudes as the number of wires is increased. Results for a wire number scan with aluminum wire arrays on the SATURN generator suggest that the observed sharp transition to high x-ray power at around 40 wires corresponds to a sharp decrease in m=0 perturbation amplitude and hence a sharp decrease in the seed perturbation for the Rayleigh-Taylor instability.

Peroxisome proliferators are a class of structurally diverse chemicals, which induce liver carcinogenesis in rodents through interaction and activation of the Peroxisome Proliferator-Activated Receptor alpha (PPARalpha). PPARalpha agonists elicit a powerful pleiotropic response, which include hypolipidaemia. We have examined the response of species that are classically unresponsive to peroxisome proliferators. Whereas hamster responds to PPARalpha agonists by hepatomegaly and induction of marker genes, the guinea pig does not undergo hepatomegaly or induction of marker genes, such as CYP4A13. Both the hamster and the guinea pig have PPARalpha, and the guinea pig receptor has been characterised to be fully functional, as demonstrated in reporter gene expression assays. However, the guinea pig PPARalpha is expressed at low levels in liver, and the currently favoured hypothesis to explain species differences in hepatic peroxisome proliferation invokes the low level of PPARalpha as the principal determinant of species responsiveness. However, the demonstration that guinea pigs and humans undergo hypolipidaemia induced by PPARalpha-agonists calls into question the mode of action of PPARalpha agonists in "non-responsive" species.

The transport of fast electrons generated by a 1 ps, 20 J, 10(19) W cm(-2), 1 microm wavelength laser pulse through 70-250 microm thick deuterated polyethylene (CD2) targets is modeled with a Fokker-Planck hybrid code in r-z geometry. Initially, electric field generation inhibits propagation, which then proceeds by the formation of a low resistivity channel due to Ohmic heating. The magnetic field generated at the edge of the channel leads to strong collimation. This is observed for a wide range of parameters. Reflection of electrons at the rear surface forms a magnetic field which focuses the incident electrons on to the rear surface and forces the reflected electrons outwards. This would lead to the formation of a small diameter plasma on the rear surface, as observed in experiments. The reflected electrons are confined to a cone by a self-generated magnetic field, enhancing energy deposition at the rear of the target.

The guinea pig does not undergo peroxisome proliferation in response to peroxisome proliferators, in contrast with other rodents. To understand the molecular basis of this phenotype, the peroxisome proliferator activated receptor alpha (PPARalpha) from guinea-pig liver was cloned; it encodes a protein of 467 amino acid residues that is similar to rodent and human PPARalpha. The guinea-pig PPARalpha showed a high substitution rate: maximum likelihood analysis was consistent with rodent monophyly, but could not exclude rodent polyphyly (P approximately 0.06). The guinea-pig PPARalpha cDNA was expressed in 293 cells and mediated the induction of the luciferase reporter gene by the peroxisome proliferator, Wy-14,643, dependent on the presence of a peroxisome proliferator response element. Moreover the PPARalpha RNA and protein were expressed in guinea-pig liver, although at lower levels than in a species which is responsive to peroxisome proliferators, the mouse. To determine whether the guinea-pig PPARalpha mediated any physiological effects, guinea pigs were exposed to two selective PPARalpha agonists, Wy-14, 643 and methylclofenapate; both compounds induced hypolipidaemia. Thus the guinea pig is a useful model for human responses to peroxisome proliferators.

Three murine peroxisome-proliferator-activated-receptor (PPAR) genes were localised to chromosome 15 (PPAR alpha), chromosome 17 (PPAR beta) and chromosome 6 (PPAR gamma). The expression of the three PPAR RNAs was determined using a specific RNase protection assay. In liver RNA, PPAR alpha was expressed at the highest level, with 20-fold lower levels of PPAR beta, and very low levels of PPAR gamma. The three PPAR RNAs showed no sex-specific differences in expression, and the levels of these transcripts were unaffected by treatment of mice with testosterone or the potent peroxisome proliferator, methylclofenapate. In agreement with this data, the level of PPAR alpha protein in liver was unchanged after treatment of mice with methylclofenapate. Investigation of the tissue-specific distribution revealed that the PPAR alpha RNA was expressed at highest levels in liver, to moderate levels in kidney and brown adipose tissue, and at low levels elsewhere. PPAR beta was expressed at moderate levels in liver, and lower levels in other tissues, including brown adipose tissue. In contrast, PPAR gamma RNA was expressed at low levels in liver or epididymal white adipose tissue and at very low levels elsewhere, but was expressed at high levels in brown adipose tissue. The tissue distribution of these receptors suggests an important role in lipid metabolism and toxicity for individual members of the PPAR family. The expression of PPAR alpha and PPAR beta RNAs was examined in 13 strains of mice, and the levels of expression varied within a fourfold range. Polymorphism in the size of PPAR alpha RNA from Swiss-Webster mice was detected, and shown to be due to a 2-bp mutation in the 3' non-coding region of PPAR alpha in Swiss Webster mice.

Twenty-five immunocompromised children with varicella were treated with oral acyclovir 800 mg, five times daily for 7 days. Two patients were transferred from the oral to the intravenous route: one had signs of varicella pneumonitis on routine X-ray, the other had continuing new lesion formation on day 4 of oral treatment. The disease healed in all patients, with no other evidence of dissemination. In an historical placebo treated group, 12 of 25 patients were transferred to intravenous acyclovir. The reduction to two of 25 is statistically significant (P < 0.01). The mean peak plasma acyclovir concentration in these patients was 6.56 mumol/l. Mild, self-limiting diarrhoea in nine patients was the only adverse event considered to be related to acyclovir. It is concluded that immunocompromised children with varicella can be treated safely and effectively with oral acyclovir. All patients should be observed closely by a physician.