Dynamics and Power Balance of Near Unity Target Gain Inertial Confinement Fusion Implosions.

The change in the power balance, temporal dynamics, emission weighted size, temperature, mass, and areal density of inertially confined fusion plasmas have been quantified for experiments that reach target gains up to 0.72. It is observed that as the target gain rises, increased rates of self-heating initially overcome expansion power losses. This leads to reacting plasmas that reach peak fusion production at later times with increased size, temperature, mass and with lower emission weighted areal densities. Analytic models are consistent with the observations and inferences for how these quantities evolve as the rate of fusion self-heating, fusion yield, and target gain increase. At peak fusion production, it is found that as temperatures and target gains rise, the expansion power loss increases to a near constant ratio of the fusion self-heating power. This is consistent with models that indicate that the expansion losses dominate the dynamics in this regime.

Predictive factors for identifying macrolide responder in treating chronic rhinosinusitis.

BACKGROUND: Low-dose macrolides (LDM) are anti-inflammatory agents with antineutrophilic activity, but patient selection for LDM therapy in treating chronic rhinosinusitis (CRS) is controversial. This study aimed to assess factors which predict LDM responders. METHODOLOGY: A prospective cohort study was performed. Patients with CRS received roxithromycin (150 mg) once daily for 12 weeks. Nasal secretions and serology were collected. Nine predictors for LDM response were assessed: nasal secretion IgE, nasal secretion IL-5, serum IgE, serum eosinophils, serum neutrophils, nasal polyps, asthma, allergy, and aspirin hypersensitivity, using receiver-operating curve analysis and multivariable logistic regression. Macrolide responders were those with sino-nasal outcome test-22 improvement, symptoms visual analogue scale decreased to ≤ ≤ ≤5, and no rescue medication. RESULTS: One hundred CRS patients (mean age 47.4 +- 14.1 years, 45% male) were enrolled. Univariable logistic regression showed local total IgE less than 5.21; and serum eosinophils less than 2.2% associated with macrolide response. Multivariate models showed local total IgE maintained an independent association with macrolide response, with an ability to discriminate between responders and non-responders of 63%. Serum total IgE, nasal secretion IL-5, serum neutrophil, nasal polyp, asthma, allergy, and aspirin hypersensitivity showed no association with LDM response. CONCLUSIONS: Low total IgE level in the nasal secretion but not in the serum, predict LDM response.

A sustainable method to reduce postoperative oxycodone discharge prescribing in a metropolitan tertiary referral hospital.

The primary objective of this quality improvement project was to measure and reduce the number of oxycodone immediate-release tablets dispensed to overnight stay surgical patients at discharge. The secondary objective was to reduce the proportion of inappropriate oxycodone immediate-release prescriptions at discharge. Interrupted time series analysis was performed in four surgical wards of St Vincent's Public Hospital, Sydney. The baseline period was from January 2005 to August 2013. Interventions and follow-up occurred until July 2017. Baseline audit of oxycodone immediate-release tablet numbers showed prescribing increased significantly with a monthly linear trend of 1.8 (95%CI = 1.4-2.3; p = 0.001) tablets/100 surgical admissions from January 2005 to August 2013. Four sequential interventions produced no significant change in the primary objective. At the end of the first month of a fifth intervention, comprising audit-feedback plus individual academic detailing, the average number of oxycodone tablets decreased by 77 (95%CI 39-115) tablets/100 surgical cases, and the postintervention linear trend was a monthly reduction of 3.2 (coefficient -3.2 (95%CI -4.5 to -1.8); p = 0.001) tablets/100 surgical admissions. Baseline audit showed 27% of oxycodone prescriptions to be inappropriate. Following our intervention, this dropped to 17% (p = 0.048), and then to 10% (p = 0.002) after 3 years.

Chronic occupational exposure to lead leads to significant mucocutaneous changes in lead factory workers.

BACKGROUND: Chronic lead toxicity is a worldwide public health problem. Lead possesses deleterious effects on many organ systems. However, little is known regarding its clinical and biophysical effects on the skin. OBJECTIVE: To investigate mucocutaneous signs and biophysical property changes in skin after chronic lead toxicity. METHODS: One hundred and eighty-seven patients who were car battery workers participated in the study. Complete history and physical examination were performed. Blood was collected for laboratory analyses. Thorough skin examination by dermatologists was carried out in 134 subjects. Additionally, 96 patients with blood lead levels (BLL) >70 µg/dL were further evaluated for skin elasticity, sebum content, transepidermal water loss (TEWL), hydration, pH and pigmentation. An equal number of age-, sex- and skin-type-matched subjects were recruited as controls. RESULTS: The mean BLL of all subjects was 74.15 ± 11.58 µg/dL. The most frequently observed signs were gingival brown pigmentation in 112 (83.6%), gingivitis in 111 (82.8%) and lead line in 66 (49.3%) patients. The lead line was found in subjects with significantly higher BLLs (adjusted mean difference 6.45, 95% CI 2.30-10.60 µg/dL, P = 0.003) and in association with gingivitis (adjusted OR 7.32, 95% CI 2.08-25.74, P = 0.002). Mean BLL of the patients who underwent biophysical assessment was 82.77 ± 9.80 µg/dL. Patients exhibited a statistically significant lower skin hydration observed by corneometer as well as elasticity. The adjusted ORs of having dry skin and lower elasticity were 15.32 (95% CI 4.41-53.24), P < 0.001) and 1.96 (95% CI 1.06-3.60), P = 0.031), respectively. These differences were not significant for sebum content, TEWL, pH and pigmentation. CONCLUSION: Importantly, even in normal-appearing skin, level of hydration and elasticity decreased in lead-intoxicated patients. These results suggest that lead might possess harmful effects on the skin at measurable levels.

Life expectancy of HIV-positive people after starting combination antiretroviral therapy: a meta-analysis.

OBJECTIVES: Life expectancy is an important indicator informing decision making in policies relating to HIV-infected people. Studies estimating life expectancy after starting combination antiretroviral therapy (cART) have noted differences between income regions. The objective of our study was to perform a meta-analysis to assess life expectancy of HIV-positive people after starting cART, and to quantify differences between low/middle- and high-income countries. METHODS: Eight cohort studies estimating life expectancy in HIV-positive people initiating cART aged ≥ 14 years using the abridged life table method were identified. Random effects meta-analysis was used to pool estimated outcomes, overall and by income region. Heterogeneity between studies was assessed with the I2 statistic. We estimated additional years of life expected after starting cART at ages 20 and 35 years. RESULTS: Overall life expectancy in high-income countries was an additional 43.3 years [95% confidence interval (CI) 42.5-44.2 years] and 32.2 years (95% CI 30.9-33.5 years) at ages 20 and 35 years, respectively, and 28.3 (95% CI 23.3-33.3) and 25.6 (95% CI 22.1-29.2) additional years, respectively, in low/middle-income countries. In low/middle-income countries, life expectancy after starting cART at age 20 years was an additional 22.9 years (95% CI 18.4-27.5 years) for men and 33.0 years (95% CI 30.4-35.6 years) for women, but was similar in the two sexes in high-income countries. In all income regions, life expectancy after starting cART increased over calendar time. CONCLUSIONS: Our results suggest that the life expectancy of HIV-positive people after starting cART has improved over time. Monitoring life expectancy into the future is important to assess how changes to cART guidelines will affect patient long-term outcomes.

Collimated Propagation of Fast Electron Beams Accelerated by High-Contrast Laser Pulses in Highly Resistive Shocked Carbon.

Collimated transport of ultrahigh intensity electron current was observed in cold and in laser-shocked vitreous carbon, in agreement with simulation predictions. The fast electron beams were created by coupling high-intensity and high-contrast laser pulses onto copper-coated cones drilled into the carbon samples. The guiding mechanism-observed only for times before the shock breakout at the inner cone tip-is due to self-generated resistive magnetic fields of ∼0.5-1 kT arising from the intense currents of fast electrons in vitreous carbon, by virtue of its specific high resistivity over the range of explored background temperatures. The spatial distribution of the electron beams, injected through the samples at different stages of compression, was characterized by side-on imaging of hard x-ray fluorescence.

Scaling the yield of laser-driven electron-positron jets to laboratory astrophysical applications.

We report new experimental results obtained on three different laser facilities that show directed laser-driven relativistic electron-positron jets with up to 30 times larger yields than previously obtained and a quadratic (∼E_{L}^{2}) dependence of the positron yield on the laser energy. This favorable scaling stems from a combination of higher energy electrons due to increased laser intensity and the recirculation of MeV electrons in the mm-thick target. Based on this scaling, first principles simulations predict the possibility of using such electron-positron jets, produced at upcoming high-energy laser facilities, to probe the physics of relativistic collisionless shocks in the laboratory.

Enhanced relativistic-electron-beam energy loss in warm dense aluminum.

Energy loss in the transport of a beam of relativistic electrons in warm dense aluminum is measured in the regime of ultrahigh electron beam current density over 2×10^{11} A/cm^{2} (time averaged). The samples are heated by shock compression. Comparing to undriven cold solid targets, the roles of the different initial resistivity and of the transient resistivity (upon target heating during electron transport) are directly observable in the experimental data, and are reproduced by a comprehensive set of simulations describing the hydrodynamics of the shock compression and electron beam generation and transport. We measured a 19% increase in electron resistive energy loss in warm dense compared to cold solid samples of identical areal mass.

Ritonavir-boosted lopinavir plus nucleoside or nucleotide reverse transcriptase inhibitors versus ritonavir-boosted lopinavir plus raltegravir for treatment of HIV-1 infection in adults with virological failure of a standard first-line ART regimen (SECOND-LINE): a randomised, open-label, non-inferiority study.

BACKGROUND: Uncertainty exists about the best treatment for people with HIV-1 who have virological failure with first-line combination antiretroviral therapy of a non-nucleoside analogue (NNRTI) plus two nucleoside or nucleotide analogue reverse transcriptase inhibitors (NtRTI). We compared a second-line regimen combining two new classes of drug with a WHO-recommended regimen. METHODS: We did this 96-week, phase 3b/4, randomised, open-label non-inferiority trial at 37 sites worldwide. Adults with HIV-1 who had confirmed virological failure (plasma viral load >500 copies per mL) after 24 weeks or more of first-line treatment were randomly assigned (1:1) to receive ritonavir-boosted lopinavir plus two or three NtRTIs (control group) or ritonavir-boosted lopinavir plus raltegravir (raltegravir group). The randomisation sequence was computer generated with block randomisation (block size four). Neither participants nor investigators were masked to allocation. The primary endpoint was the proportion of participants with plasma viral load less than 200 copies per mL at 48 weeks in the modified intention-to-treat population, with a non-inferiority margin of 12%. This study is registered with ClinicalTrials.gov, number NCT00931463. FINDINGS: We enrolled 558 patients, of whom 541 (271 in the control group, 270 in the raltegravir group) were included in the primary analysis. At 48 weeks, 219 (81%) patients in the control group compared with 223 (83%) in the raltegravir group met the primary endpoint (difference 1·8%, 95% CI -4·7 to 8·3), fulfilling the criterion for non-inferiority. 993 adverse events occurred in 271 participants in the control group versus 895 in 270 participants in the raltegravir group, the most common being gastrointestinal. INTERPRETATION: The raltegravir regimen was no less efficacious than the standard of care and was safe and well tolerated. This simple NtRTI-free treatment strategy might extend the successful public health approach to management of HIV by providing simple, easy to administer, effective, safe, and tolerable second-line combination antiretroviral therapy. FUNDING: University of New South Wales, Merck, AbbVie, the Foundation for AIDS Research.

Comparative evaluation of three commercial systems for detection of high-risk human papillomavirus in cervical and vaginal ThinPrep PreservCyt samples and correlation with biopsy results.

Genital human papillomavirus (HPV) is the etiologic agent of more than 99% of all cervical cancers worldwide, with 14 genotypes being considered oncogenic or "high risk" because of their association with severe dysplasia and cervical carcinoma. Among these 14 high-risk types, HPV-16 and -18 account for approximately 70% of cervical cancers. The aim of this study was to evaluate three FDA-approved HPV nucleic acid-based tests for the ability to predict high-grade cervical intraepithelial neoplasias (CIN2 or worse) in corresponding tissue biopsy specimens. Residual specimens (total n = 793, cervical n = 743, vaginal n = 50) collected in ThinPrep PreservCyt medium with a cytologic result of ≥ atypical squamous cells of undetermined significance were tested by the Hybrid Capture 2 (HC2) assay (Qiagen, Gaithersburg, MD), the cobas HPV test (Roche Diagnostics, Indianapolis, IN), and the APTIMA HPV assay (Hologic, San Diego, CA). Genotyping for HPV-16 and HPV-18 was simultaneously performed by the cobas HPV test. Results were compared to cervical or vaginal biopsy findings, when they were available (n = 350). Among the 350 patients with corresponding biopsy results, 81 (23.1%) showed ≥ CIN2 by histopathology. The ≥ CIN2 detection sensitivity was 91.4% by the cobas and APTIMA assays and 97.5% by HC2 assay. The specificities of the cobas, APTIMA, and HC2 assays were 31.2, 42.0, and 27.1%, respectively. When considering only positive HPV-16 and/or HPV-18 genotype results, the cobas test showed a sensitivity and a specificity of 51.9 and 86.6%, respectively. While the HC2, cobas, and APTIMA assays showed similar sensitivities for the detection of ≥ CIN2 lesions, the specificities of the three tests varied, with the greatest specificity (86.6%) observed when the HPV-16 and/or HPV-18 genotypes were detected.

In-vivo and ex-vivo tests for culprit drugs identification in severe cutaneous adverse drugs reactions.

Drug causality assessment in severe cutaneous adverse reactions (SCARs) remains challenging. We investigated the usefulness of in-vivo drug patch tests (PT), ex-vivo interferon (IFN)-γ enzyme-linked immunospot (ELISpot) assay, and lymphocyte transformation test (LTT) in 30 SCARs patients within the past 36 months. Drug PT yielded a 20% positivity rate (n = 6), while IFN-γ ELISpot and LTT showed positive rates of 56.67% (n = 17) and 41.38% (n = 12), respectively. Combining the three tests resulted in an overall positive rate of 66.67% (n = 20) of cases. IFN-γ ELISpot offered additional positivity, especially with oxypurinol. Employing a combined diagnostic approach may enhance the chances of obtaining a positive result.

Observations and properties of the first laboratory fusion experiment to exceed a target gain of unity.

An indirect-drive inertial fusion experiment on the National Ignition Facility was driven using 2.05 MJ of laser light at a wavelength of 351 nm and produced 3.1±0.16 MJ of total fusion yield, producing a target gain G=1.5±0.1 exceeding unity for the first time in a laboratory experiment [Phys. Rev. E 109, 025204 (2024)10.1103/PhysRevE.109.025204]. Herein we describe the experimental evidence for the increased drive on the capsule using additional laser energy and control over known degradation mechanisms, which are critical to achieving high performance. Improved fuel compression relative to previous megajoule-yield experiments is observed. Novel signatures of the ignition and burn propagation to high yield can now be studied in the laboratory for the first time.

Tobacco and alcohol-related interventions for people with mild/moderate intellectual disabilities: a systematic review of the literature.

BACKGROUND: The behavioural determinants of health among people with mild/moderate intellectual disabilities (ID) are of increasing concern. With the closure of long-stay institutions, more people with ID are living in the community. As they lead more ordinary and less restricted lives, people with ID may be exposed to social and environmental pressures that encourage them to adopt behaviours that impact negatively on their health. Levels of smoking and alcohol consumption in this client group are of particular concern. METHODS: We undertook a mixed method review of the literature, aiming to assess the Feasibility, Appropriateness, Meaningfulness and Effectiveness (FAME) of interventions designed to address the use of tobacco and/or alcohol in people with mild/moderate ID. Key electronic databases were searched (e.g., Medline, Cochrane Register of Controlled Trials, PsycINFO) from 1996 to 2011. The search was developed using appropriate subject headings and key words (e.g., intellectual disability, tobacco use, alcohol drinking, health promotion). On completion of the database searches, inclusion/exclusion criteria, based on an adaptation of the PICO framework (Population, Intervention, Comparison, Outcomes), were applied. Methodological quality was assessed using a seven-point rating scale. RESULTS: Database searches identified 501 unique records, of which nine satisfied the inclusion criteria. Four focused on tobacco, three on alcohol and two on both tobacco and alcohol. Located in the U.K., the U.S.A. and Australia, the studies aimed to increase knowledge levels and/or change behaviour (e.g., to encourage smoking cessation). One was a randomised controlled trial, one a quasi-experiment and the others were before and after studies and/or case studies. Methodological quality was poor or moderate. The combined studies had a sample size of 341, with ages ranging from 14 to 54 years. The interventions were delivered by professionals (e.g., in health, social care, education) during sessions that spanned a period of three weeks to one academic year. The studies highlighted a number of important issues linked to the appropriateness of interventions for this client group (e.g., use of pictures, quizzes, role play, incentives); however, in the majority of cases the interventions appeared to lack a theoretical framework (e.g., behaviour change theory). The appropriateness of the outcome measures for use with this client group was not tested. One study discussed feasibility (teachers delivering lessons on alcohol and tobacco) and only one was informative in terms of effectiveness, i.e., increasing knowledge of the health and social dangers of smoking and excessive alcohol consumption. CONCLUSIONS: This review is the first to systematically collate evidence on tobacco and alcohol-related interventions for people with ID. While there is currently little evidence to guide practice, the review delivers clear insights for the development of interventions and presents a strong case for more robust research methods. In particular there is a need to test the effectiveness of interventions in large-scale, well-designed trials and to ensure that outcome measures are developed/tailored appropriately for this client group.

An integrated model for simulating nitrogen trading in an agricultural catchment with complex hydrogeology.

Nitrogen loads to several New Zealand lakes are dominated by nonpoint runoff from pastoral farmland which adversely affects lake water quality. A 'cap and trade' scheme is being considered to help meet targets set for nitrogen loads to Lake Rotorua, and a numerical model, NTRADER, has been developed to simulate and compare alternative schemes. NTRADER models both the geophysics of nitrogen generation and transport, including groundwater lag times, and the economics of 'cap and trade' schemes. It integrates the output from several existing models, including a farm-scale nitrogen leaching and abatement model, a farm-scale management economic model, and a catchment-scale nitrogen transport model. This paper details modeling methods and compares possible trading program design features for the Lake Rotorua catchment. Model simulations demonstrate how a cap and trade program could be used to effectively achieve challenging environmental goals in the targeted catchment. However, results also show that, due to complex hydrogeology, satisfactory environmental outcomes may be not achieved unless groundwater lag times are incorporated into the regulatory scheme. One way to do this, as demonstrated here, would be to explicitly include lag times in the cap and trade program. The utility of the model is further demonstrated by quantifying relative differences in abatement costs across potential regulatory schemes.

Neutron time of flight (nToF) detectors for inertial fusion experiments.

Neutrons generated in Inertial Confinement Fusion (ICF) experiments provide valuable information to interpret the conditions reached in the plasma. The neutron time-of-flight (nToF) technique is well suited for measuring the neutron energy spectrum due to the short time (100 ps) over which neutrons are typically emitted in ICF experiments. By locating detectors 10s of meters from the source, the neutron energy spectrum can be measured to high precision. We present a contextual review of the current state of the art in nToF detectors at ICF facilities in the United States, outlining the physics that can be measured, the detector technologies currently deployed and analysis techniques used.

Dynamics of cognitive change in HIV-infected individuals commencing three different initial antiretroviral regimens: a randomized, controlled study.

BACKGROUND: Improvements in neurocognitive (NC) function have been associated with commencing antiretroviral therapy in HIV-infected subjects. However, the dynamics of such improvements are poorly understood. METHODS: We assessed changes in NC function via a validated computerized battery (CogState™, Melbourne, Victoria, Australia) at baseline and after 24 and 48 weeks in a subset of therapy-naïve neuro-asymptomatic HIV-infected subjects, randomized to commence three different antiretroviral regimens. RESULTS: Of 28 subjects enrolled in the study, nine, eight and 11 were randomly allocated to commence tenofovir/emtricitabine with efavirenz (arm 1), atazanavir/ritonavir (arm 2) and zidovudine/abacavir (arm 3), respectively. Overall improvements in NC function were observed at week 24 and function continued to improve at week 48 (changes in z-score for overall cognitive global score of 0.16 and 0.18 at weeks 24 and 48, respectively). Within the NC speed domains, generally greater improvements were observed in arms 2 and 3, compared with arm 1 (changes in z-score for composite speed scores at weeks 24/48 of 0.16/0.16, -0.29/-0.24 and -0.15/-0.31 in arms 1, 2 and 3, respectively; P = 0.04 for change at week 48 in arm 3 versus arm 1). Finally, improvements in executive function occurred later (only observed at week 48) and were driven by improvements in arm 3 (z-score changes of 0.23, 0.06 and -0.78 in arms 1, 2 and 3, respectively; P = 0.02 for change in arm 3 versus arm 1). CONCLUSION: Improvements in NC function continue over the first year after initiating antiretroviral therapy in neuro-asymptomatic HIV-infected subjects.

Postoperative omental infarction following colonic resection.

AIM: To illustrate the computed tomography (CT) appearances and natural history of postoperative omental infarction following colonic resection and to highlight the important clinical implications of this radiological diagnosis. MATERIALS AND METHODS: Over a 3 year period, 15 patients with a history of colonic resection were identified as having a CT diagnosis of postoperative omental infarction. Relevant clinical and pathological data were retrospectively collected from the institution's electronic patient records system and all relevant imaging was reviewed, including serial CT images in 10 patients. RESULTS: A diagnosis of postoperative omental infarction was made in symptomatic and asymptomatic patients who had undergone open or laparoscopic colonic resection for benign or malignant disease. CT appearances ranged from diffuse omental stranding to discrete masses, which typically appeared within weeks of surgery and could persist for years. In four (36%) of the patients with colorectal cancer, the CT appearances raised concern for recurrent malignancy, but percutaneous biopsy and/or serial CT allowed a confident diagnosis of omental infarction to be made. Although most cases were self-limiting, three (20%) cases were complicated by secondary infection and required radiological or surgical intervention. CONCLUSION: Postoperative omental infarction is an under-recognized complication of colonic resection. It has the potential to mimic recurrent malignancy and may require radiological or surgical intervention for secondary infection.