Accuracy of chest x-ray screening of silica-exposed miners for tuberculosis.

BACKGROUND: The World Health Organization recommends systematic chest X-ray (CXR) screening for tuberculosis (TB) in silica-exposed workers. However, evidence on the accuracy of CXR screening in such populations is lacking. AIMS: To measure the accuracy of CXR screening for active TB in silica-exposed miners, in a population with a high prevalence of silicosis, post-TB lung disease and HIV. METHODS: A secondary analysis of data from a miner screening programme in Lesotho was undertaken. We measured the performance of CXR (in participants with and without cough) for 'abnormalities suggestive of TB' against Xpert MTB/RIF (Xpert). The sample size was 2572 and positive Xpert prevalence was 3%. RESULTS: CXR alone had high sensitivity (0.93, 95% confidence interval [CI] 0.87-0.99), but low specificity (0.41, 95% CI 0.39-0.42). Requiring cough and a positive CXR increased specificity (0.79, 95% CI 0.77-0.81), resulting in reduced sensitivity (0.41, 95% CI 0.30-0.52). There was no difference in CXR accuracy by HIV status. However, specificity was markedly reduced in the presence of silicosis (from 0.70, 95% CI 0.68-0.72, to 0.03, 95% CI 0.02-0.04) or past TB history (from 0.59, 95% CI 0.56-0.62 to 0.27, 95% CI 0.25-0.29). Throughout, positive predictive value remained very low (5%) and negative predictive value very high (99%). CONCLUSIONS: CXR screening accurately identifies TB-negative CXRs in this population, but post-TB lung disease and silicosis would result in a high proportion of Xpert-negative referrals and an increased risk of unneeded empirical treatment. Adapted screening algorithms, practitioner training and digital access to previous mining CXRs are needed.

Measurement of the ν_{e}-Nucleus Charged-Current Double-Differential Cross Section at ⟨E_{ν}⟩=2.4 GeV Using NOvA.

The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using 8.02×10^{20} protons-on-target in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by ≃17% systematic rather than the ≃7.4% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on Q^{2} (squared four-momentum transfer) and energy, in the range 1 GeV≤E_{ν}<6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs Q^{2}.

Reforming the workers' compensation process for occupational lung disease among miners in South Africa: an efficiency study of claims assessment.

PURPOSE: The large burden of silicosis and tuberculosis (TB) in the South African mining industry, coupled with an under-resourcing of the compensation agencies responsible for certifying occupational lung disease, have resulted in serious backlogs. This work aimed to measure the efficiency gains from triaging occupational lung disease claims using claim type, years of mining exposure and computer aided detection (CAD) to save on scarce medical adjudicators. METHODS: During 2020, the compensation authority started to triage claims for TB and those of miners with < 10 years of service to two-person panels instead of the four-person panel plus radiologist used previously. Efficiency gain was calculated in medical person-units saved and reduction in delays. Different service thresholds predictive of silicosis were simulated, as well as the impact of pre-classification of chest X-rays with CAD using different combinations of sensitivity and specificity. RESULTS: The new triage system saved 20.3% in person-time units and reduced delays by 10-20 days. Without CAD the greatest efficiency gain (28%) was projected from dispensing with a mining service threshold and routing all non-TB claims to the small panels at the outset. Simulation of four different CAD sensitivity/specificity combinations yielded efficiency gains of 18.2-36.1%, with 31.1% judged the most realistic. Use of sensitivity of close to 100% would not be feasible because of the very low resulting specificity. CONCLUSION: Pre-adjudication triage of claims at the compensation agency is capable of saving a substantial proportion of adjudicator time and reducing certification delays. Additional efficiency gains are achievable by referring all claims to small panels to begin with and improvement of CAD performance for this ex-miner population.

Search for Active-Sterile Antineutrino Mixing Using Neutral-Current Interactions with the NOvA Experiment.

This Letter reports results from the first long-baseline search for sterile antineutrinos mixing in an accelerator-based antineutrino-dominated beam. The rate of neutral-current interactions in the two NOvA detectors, at distances of 1 and 810 km from the beam source, is analyzed using an exposure of 12.51×10^{20} protons-on-target from the NuMI beam at Fermilab running in antineutrino mode. A total of 121 of neutral-current candidates are observed at the far detector, compared to a prediction of 122±11(stat.)±15(syst.) assuming mixing only between three active flavors. No evidence for ν[over ¯]_{µ}→ν[over ¯]_{s} oscillation is observed. Interpreting this result within a 3+1 model, constraints are placed on the mixing angles θ_{24}<25° and θ_{34}<32° at the 90% C.L. for 0.05 eV^{2}≤Δm_{41}^{2}≤0.5 eV^{2}, the range of mass splittings that produces no significant oscillations at the near detector. These are the first 3+1 confidence limits set using long-baseline accelerator antineutrinos.

Measurement of the Neutrino Mixing Angle θ_{23} in NOvA.

This Letter reports new results on muon neutrino disappearance from NOvA, using a 14 kton detector equivalent exposure of 6.05×10^{20} protons on target from the NuMI beam at the Fermi National Accelerator Laboratory. The measurement probes the muon-tau symmetry hypothesis that requires maximal θ_{23} mixing (θ_{23}=π/4). Assuming the normal mass hierarchy, we find Δm_{32}^{2}=(2.67±0.11)×10^{-3} eV^{2} and sin^{2}θ_{23} at the two statistically degenerate values 0.404_{-0.022}^{+0.030} and 0.624_{-0.030}^{+0.022}, both at the 68% confidence level. Our data disfavor the maximal mixing scenario with 2.6σ significance.

Constraints on Oscillation Parameters from ν_{e} Appearance and ν_{µ} Disappearance in NOvA.

Results are reported from an improved measurement of ν_{µ}→ν_{e} transitions by the NOvA experiment. Using an exposure equivalent to 6.05×10^{20} protons on target, 33 ν_{e} candidates are observed with a background of 8.2±0.8 (syst.). Combined with the latest NOvA ν_{µ} disappearance data and external constraints from reactor experiments on sin^{2}2θ_{13}, the hypothesis of inverted mass hierarchy with θ_{23} in the lower octant is disfavored at greater than 93% C.L. for all values of δ_{CP}.

Rhabdomyolysis with acute tubular necrosis following occupational inhalation of thinners.

Thinners are mixtures of organic solvents commonly containing toluene, xylene, acetone, hexane, benzene and methyl isobutyl ketone. This report describes a case of rhabdomyolysis with acute tubular necrosis and renal failure, most likely attributable to toluene, following occupational exposure to thinners while cleaning a steel water tank. These adverse health effects have previously been reported following acute poisoning or intentional inhalation by drug abusers, but rarely in the occupational setting. Poor working conditions, lack of health and safety training and delayed treatment contributed to the onset and severity of the patient's complications. This case emphasizes the need for strict control measures, including adequate ventilation, training on working in confined spaces, appropriate personal protective equipment and emergency rescue procedures in such settings. In addition, rhabdomyolysis, acute tubular necrosis and renal failure should be added to safety data material as possible complications of excessive inhalation of thinners.

Deep vein thrombosis following prolonged kneeling: a case report.

This report describes a fibreglass mould maker in the yacht building industry who developed a deep vein thrombosis (DVT) after 6 weeks of working in a kneeling position. We propose that his prolonged kneeling combined with constrictive knee pad straps caused vascular compression, precipitating his DVT. A hypercoagulability diathesis was suspected but not confirmed. Operator and employer education, modified work practices and strapless knee pads are suggested as possible preventive measures.

Disulfiram reaction in an artist exposed to solvents.

This case report describes an artist on treatment for alcoholism with disulfiram (Antabuse) who suffered chronic symptoms similar to those of a disulfiram alcohol reaction, which we attribute to his occupational exposure to products containing alcohol and other solvents. Symptoms abated with strict precautions to prevent exposure, although gradually returned over the course of months, causing him eventually to stop the medication. Medical practitioners should be aware of possible adverse interactions between occupational solvent exposures and disulfiram.

Lung function loss in relation to silica dust exposure in South African gold miners.

OBJECTIVE: To estimate exposure-response relationships between respirable dust, respirable quartz and lung function loss in black South African gold miners. METHODS: 520 mineworkers aged >37 years were enrolled in a cross-sectional study. Gravimetric dust measurements were used to calculate cumulative respirable dust and quartz exposures. Excess lung function loss was defined as predicted minus observed forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). The association between excess loss and exposure was estimated, adjusting for smoking, tuberculosis and silicosis. RESULTS: Mean service length was 21.8 years, mean respirable dust 0.37 mg/m(3) and mean respirable quartz 0.053 mg/m(3). After adjustment, 1 mg-yr/m(3) increase in cumulative respirable dust exposure was associated with 18.7 ml mean excess loss in FVC [95% confidence interval (CI) 0.3, 37.1] and 16.2 ml in FEV1 (95% CI -0.3, 32.6). Mean excess loss with silicosis was 224.1 ml in FEV1 and 123.6 ml in FVC; with tuberculosis 347.4 ml in FEV1 and 264.3 ml in FVC. CONCLUSION: Despite a healthy worker effect, lung function loss was demonstrable whether due to silicosis, tuberculosis or an independent effect of dust. A miner working at a respirable dust intensity of 0.37 mg/m(3) for 30 years would lose on average an additional 208 ml in FVC (95% CI 3, 412) in the absence of other disease, an impact greater than that of silicosis and comparable to that of tuberculosis. Improved dust control on the South African gold mines would reduce the risk of silicosis, tuberculosis and lung function impairment.

Understanding the effects of neutron scattering for neutron-yield-isotropy measurements at the NIF.

Neutron-yield diagnostics at the NIF have been upgraded to include 48 detectors placed around the NIF target chamber to assess the DT-neutron-yield isotropy for inertial confinement fusion experiments. Real-time neutron-activation detectors are used to understand yield asymmetries due to Doppler shifts in the neutron energy attributed to hotspot motion, variations in the fuel and ablator areal densities, and other physics effects. In order to isolate target physics effects, we must understand the contribution due to neutron scattering associated with the different hardware configurations used for each experiment. We present results from several calibration experiments that demonstrate the ability to achieve our goal of 1% or better precision in determining the yield isotropy.

LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12.

Expression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and correlates with the in vivo oncogenicity of this virus. In primary embryonal fibroblasts (H-2b) that express transgenic swine class I antigen (PD1), Ad12-mediated transformation results in inhibition in transport of newly synthesized class I molecules, as well as significant reduction in transporter associated with antigen presentation (TAP) gene expression. In this report we show that reexpression of TAP molecules either by stable transfection of mouse TAP genes or by infection with recombinant vaccinia viruses expressing human TAP genes, only partially reconstitutes the expression and transport of the class I molecules. Further analysis of Ad12-transformed cells revealed that the expression of both LMP2 and LMP7, but not of other proteasome complex components, was downregulated, resulting in altered proteolytic activities of the 20S proteasomes. Reconstitution of both TAP and LMP expression resulted in complete restoration of PD1 cell surface expression and enhanced expression of the endogenous H-2D(b) molecules encoded by recombinant vaccinia viruses, in reconstituted Ad12-transformed cells, efficient transport of H-2 class I molecules could only be achieved by treatment of the cells with gamma-interferon. These data suggest that an additional factor(s) that is interferon-regulated plays a role in the biosynthetic pathway of the class I complex, and that its function is deficient in this cell system. Thus, Ad12 viral transformation appears to suppress the expression of multiple genes that are important for antigen processing and presentation, which allows such transformed cells to escape immune surveillance. This coordinate downregulation of immune response genes must likely occur through their use of common regulatory elements.

Downregulation of peptide transporter genes in cell lines transformed with the highly oncogenic adenovirus 12.

The expression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and correlates with the high oncogenicity of this virus. In primary embryonal fibroblasts from transgenic mice that express both endogenous H-2 genes and a miniature swine class I gene (PD1), Ad12-mediated transformation results in suppression of cell surface expression of all class I antigens. Although class I mRNA levels of PD1 and H-2Db are similar to those in nonvirally transformed cells, recognition of newly synthesized class I molecules by a panel of monoclonal antibodies is impaired, presumably as a result of inefficient assembly and transport of the class I molecules. Class I expression can be partially induced by culturing cells at 26 degrees C, or by coculture of cells with class I binding peptides at 37 degrees C. Analysis of steady state mRNA levels of the TAP1 and TAP2 transporter genes for Ad12-transformed cell lines revealed that they both are significantly reduced, TAP2 by about 100-fold and TAP1 by 5-10-fold. Reconstitution of PD1 and H-2Db, but not H-2Kb, expression is achieved in an Ad12-transformed cell line by stable transfection with a TAP2, but not a TAP1, expression construct. From these data it may be concluded that suppressed expression of peptide transporter genes, especially TAP2, in Ad12-transformed cells inhibits cell surface expression of class I molecules. The failure to fully reconstitute H-2Db and H-2Kb expression indicates that additional factors are involved in controlling class I gene expression in Ad12-transformed cells. Nevertheless, these results suggest that suppression of peptide transporter genes might be an important mechanism whereby virus-transformed cells escape immune recognition in vivo.

Excess lung function decline in gold miners following pulmonary tuberculosis.

BACKGROUND: Few if any studies of the association between pulmonary tuberculosis (TB) and lung function loss have had access to premorbid lung function values. METHODS: Using a retrospective cohort design, the study recruited employed South African gold miners who had undergone a pulmonary function test (PFT) between January 1995 and August 1996. The 'exposed' group comprised 185 miners treated for pulmonary TB after the initial PFT and the 'unexposed' group comprised 185 age-matched miners without TB. All participants had a follow-up PFT between April and June 2000. The outcome of interest was decline in lung function during the follow-up period as measured by forced vital capacity (FVC) and forced expiratory volume in 1 s(FEV(1)). RESULTS: After controlling for age, height, baseline lung function, silicosis, years of employment, smoking and other respiratory diagnoses, pulmonary TB during the follow-up period was associated with a mean excess loss of 40.3 ml/year in FEV(1) (95% CI 25.4 to 55.1) and 42.7 ml/year in FVC (95% CI 27.0 to 58.5). Lung function loss was greater among those with more severe or later clinical presentation of TB. Breathlessness was twice as common among TB cases (OR 2.20, 95% CI 1.18 to 4.11). CONCLUSION: There is a need for greater clinical recognition of the long-term respiratory consequences of treated pulmonary TB. Early detection of TB would help to reduce these sequelae and remains a priority, particularly in a workforce already subject to silica dust disease. However, strategies such as dust control, worker education about TB and dust and TB preventive therapy are also needed to avert the disease itself.

Workers' compensation claims for occupational tuberculosis in South African health workers: Outcomes and workers' experiences.

BACKGROUND: Given the elevated risk of tuberculosis (TB), including drug-resistant disease, experienced by health workers in South Africa (SA), effective workers' compensation for occupational TB is a legal right and an essential social benefit. OBJECTIVES: To investigate the experience of the workers' compensation system among health workers who suffered from TB while working in public service facilities in Western Cape Province, SA. METHODS: In this case series with a qualitative component, 300 claims for occupational TB in health workers were sampled from the provincial health department database of claims submitted. Claim status for each case was ascertained. An attempt was made to contact each health worker for a telephonic interview consisting of both closed- and open-ended (qualitative) questions. Fifty-one interviews were completed. RESULTS: In nearly half of the cases, there was no record of claim status on the state Compensation Fund website. Of the 51 interviewees, only one had received all the compensation benefits for their particular claim circumstances. Health workers' experience of having their cases reported for compensation purposes was marred by perception of poor communication and administration. The experience of contracting TB was further characterised by surprise, perceptions of stigma, financial burden and ongoing ill-health. CONCLUSIONS: Affected health workers' experience of the workers' compensation system was mostly negative, adding to the burden of being ill with TB. Education of management and clinicians, improvement in communication, and timeous and regular checking of claim status and of payment of applicable compensation are required at the provincial level. Dedicated facility-based occupational health units are needed, with a staff complement of knowledgeable persons trusted by their colleagues. However, the effectiveness of the system is ultimately dependent on the ability of the Compensation Fund to register and display claims timeously and administer compensation expeditiously.

Computer-aided detection for tuberculosis and silicosis in chest radiographs of gold miners of South Africa.

BACKGROUND: For over one hundred years, the gold mining sector has been a considerable source of tuberculosis (TB) and silicosis disease burden across Southern Africa. Reading chest radiographs (CXRs) is an expert and time-intensive process necessary for the screening and diagnosis of lung disease and the provision of evidence for compensation claims. Our study explores the use of computer-aided detection (CAD) of TB and silicosis in CXRs of a population with a high incidence of both diseases.METHODS: A set of 330 CXRs with human expert-determined classifications of silicosis, TB, silcotuberculosis and normal were provided to four health technology companies. The ability of each of their respective CAD systems to predict disease was assessed using receiver operating characteristic curve analysis of the under the curve metric.RESULTS: Three of the four systems differentiated accurately between TB and normal images, while two differentiated accurately between silicosis and normal images. Inclusion of silicotuberculosis images reduced each system's ability to detect either disease. In differentiating between any abnormal from normal CXR, the most accurate system achieved both a sensitivity and specificity of 98.2%.CONCLUSION: The current ability of CAD to differentiate between TB and silicosis is limited, but its use as a mass screening tool for both diseases shows considerable promise.

On the system stability and calibration of the image plate/scanner system for plasma diagnosis at the National Ignition Facility.

At the National Ignition Facility (NIF), storage phosphor image plates (IP) are used extensively for recording x-rays, charged particles, and neutrons. For x-ray imaging and spectroscopy, absolute and relative calibrations are important for extracting plasma information from the diagnostics. We use Fuji MS, SR, and TR image plates that have been cut to fit custom diagnostic envelopes. The image plates are scanned on a General Electric FLA 7000 IP flying spot scanner. Calibrations for sensitivity, spatial scale, and temperature dependent fade are applied. During a set of recent calibrations, we noticed large shifts in the absolute calibration of the image plate system. The possible source of these shifts is discussed. We discuss scanner stability and a method for calibration. We discuss the fade and temperature effects of the image plates and how this correction is applied within the NIF environment. We also compare our NIF GE FLA 7000 IP scanner with a new General Electric Amersham Typhoon IP scanner.

Simultaneous visualization of wall motion, beam propagation, and implosion symmetry on the National Ignition Facility (invited).

Achieving a symmetric implosion in National Ignition Facility indirect drive targets requires understanding and control of dynamic changes to the laser power transport in the hohlraum. We developed a new experimental platform to simultaneously visualize wall-plasma motion and dynamic laser power transport in the hohlraum and are using it to investigate correlations of these measurements with the imploded capsule symmetry. In a series of experiments where we made one single parameter variation, we show the value of this new platform in developing an understanding of laser transport and implosion symmetry. This platform also provides a new way to evaluate dynamic performance of advanced hohlraum designs.

Study of exclusive charmless semileptonic B decays and |Vub|.

We study semileptonic B decay to the exclusive charmless states pi, rho/omega, eta, and eta;{'} using the 16 fb(-1) CLEO Upsilon(4S) data sample. We find B(B0-->pi-l+nu)=(1.37+/-0.15stat+/-0.11sys)x10(-4) and B(B0-->rho-l+nu)=(2.93+/-0.37stat+/-0.37sys)x10(-4) and find evidence for B+-->eta'l+nu, with B(B+-->eta'l+nu)=(2.66+/-0.80stat+/-0.56sys)x10(-4). From our B-->pilnu rate for q2>16 GeV2 and lattice QCD, we find |Vub|=(3.6+/0.4stat+/0.2syst-0.4thy+0.6)x10(-3) [corrected]

Randomised controlled trial of isoniazid preventive therapy in South African adults with advanced HIV disease.

BACKGROUND: Tuberculosis (TB) preventive therapy is not effective in human immunodeficiency virus (HIV) infected adults with negative tuberculin skin tests (TSTs). However, there are insufficient data on patients with advanced HIV disease from high TB incidence areas. METHODS: We conducted a randomised, double-blind, controlled trial comparing isoniazid (INH) with placebo among TST-negative adults with World Health Organization Stage 3 or 4 HIV disease. INH/placebo was administered for 12 months by patient-nominated supervisors. TST-positive participants were given open-label INH. Participants, who did not have access to antiretroviral therapy (ART), were followed up for 24 months with 6-monthly sputum culture and chest radiography. RESULTS: A total of 118 participants were enrolled: TST was negative in 98. In the randomised arms, the incidence of TB was 18/100 person-years (py) in the INH arm and 11.6/100 py in the placebo arm (hazard ratio 1.59, 95%CI 0.57-4.49). There were no significant differences in mortality, hospitalisation rate or CD4+ lymphocyte decline. INH/placebo adherence was 85%, and was significantly higher among participants with work-based treatment supervisors. CONCLUSIONS: We did not find any association between INH preventive therapy and reductions in incident TB among TST-negative adults with advanced HIV disease, but the study had limited statistical power. High levels of adherence were observed with patient-nominated supervisors.