Development of a hardened THz energy meter for use on the kilojoule-scale, short-pulse OMEGA EP laser.

A highly adaptable and robust terahertz (THz) energy meter is designed and implemented to detect energetic THz pulses from high-intensity (>1018 W/cm2) laser-plasma interactions on the OMEGA EP. THz radiation from the laser driven target is detected by a shielded pyrometer. A second identical pyrometer is used for background subtraction. The detector can be configured to detect THz pulses in the 1 mm to 30 µm (0.3- to 10-THz) range and pulse energies from joules to microjoules via changes in filtration, aperture size, and position. Additional polarization selective filtration can also be used to determine the THz pulse polarization. The design incorporates significant radiation and electromagnetic pulse shielding to survive and operate within the OMEGA EP radiation environment. We describe the design, operational principle, calibration, and testing of the THz energy meter. The pyrometers were calibrated using a benchtop laser and show linear sensitivity to up to 1000 nJ of absorbed energy. The initial results from four OMEGA EP THz experiments detected up to ∼15µJ at the detector, which can correspond to hundreds of mJ depending on THz emission and reflection models.

Atrial fibrillation and mortality in outpatients with heart failure in Tanzania: a prospective cohort study.

OBJECTIVE: In recent years, the prevalence and mortality of heart failure (HF) and other associated cardiovascular diseases have doubled in sub-Saharan Africa (SSA). Studies in high-income countries indicate that HF with concurrent atrial fibrillation (AF) is linked to increased mortality. Our objective was to determine the incidence and clinical outcomes of AF among patients with HF in SSA. DESIGN: A prospective cohort study using data collected between October 2018 and May 2020. SETTING: Outpatient clinic at a tertiary hospital in Mwanza, Tanzania. PARTICIPANTS: 303 adult participants (aged ≥18 years) with HF as defined by the European Society of Cardiology guidelines (2016) and 100 adults with HF as defined by clinical criteria alone were enrolled into the study. Patients with comorbid medical condition that had prognosis of <3 months (ie, advance solid tumours, advance haematological malignancies) were excluded. METHODS: Participants were screened for AF, and their medical history, physical examinations and sociodemographic information were obtained. Multivariable logistic regression models were used to examine factors associated with AF incidence. Cox regression models were used to analyse 3-month mortality and its associated risk factors. RESULTS: We enrolled 403 participants with HF (mean age 60±19 years, 234 (58%) female). The AF prevalence was 17%. In multivariable models, factors associated with AF were low income, alcohol consumption and longer duration of HF. At the end of the 3-month follow-up, 120 out of 403 (30%) participants died, including 44% (31/70) of those with AF. Higher heart rate on ECG, more severe New York Heart Association HF class, rural residence and anaemia were significantly correlated with mortality. CONCLUSION: AF is common, underdiagnosed and is associated with significant mortality among outpatients with HF in Tanzania (HR 1.749, 95% CI 1.162 to 2.633, p=0.007). Our findings additionally identify tachycardia (>110 bpm, HR 1.879, 95% CI 1.508 to 2.340, p<0.001) as an easily measurable, high-impact physical examination finding for adverse outcomes in patients with HF.

Depression screening in HIV-positive Tanzanian adults: comparing the PHQ-2, PHQ-9 and WHO-5 questionnaires.

BACKGROUND: HIV-positive individuals are at significantly increased risk of depression. In low- and middle-income countries, depression is frequently under-detected, hampered by a lack of data regarding available screening tools. The 5-item World Health Organization Well-Being Index (WHO-5) is widely used to screen for depression, yet its validity in African adults with HIV has yet to be examined. METHODS: In this cross-sectional study, we enrolled HIV-positive adults presenting to an outpatient HIV clinic in Mwanza, Tanzania. Patients were administered the Patient Health Questionnaires (PHQ)-2/9 and WHO-5 questionnaires. The rate of positive screens was calculated. Fisher's exact test and Pearson's correlation coefficients between PHQ-2/9 and WHO-5 scores were calculated. RESULTS: We enrolled 72 HIV-positive adults: rates of positive depression screen were 62.5%, 77.8%, and 47.2% according to PHQ-2, PHQ-9, and WHO-5, respectively. PHQ and WHO results for depression were significantly associated (Fisher's exact test: PHQ-2 v. WHO-5, p = 0.028; PHQ-9 v. WHO-5, p = 0.002). The level of correlation between PHQ and WHO results for depression was moderate (Pearson's correlation coefficient: PHQ-2 v. WHO-5 -0.3289; PHQ-9 v. WHO-5 -0.4463).Per Mantel-Haenszel analysis, screening results were significantly more concordant among patients in the following strata: men, age >40, Sukuma ethnicity, Christian, unmarried, self-employed, at least primary school education completed, and higher than the median income level. CONCLUSIONS: WHO-5 scores correlated well with those of the PHQ-9, suggesting that the WHO-5 represents a valid screening tool. The concordance of PHQ-9 and WHO-5 results was poorer in marginalized socioeconomic groups. Positive depression screens were exceedingly common among HIV-positive Tanzanian adults according to all three questionnaires.

Bottom-up Meets Top-down: Complementary Physiologically Based Pharmacokinetic and Population Pharmacokinetic Modeling for Regulatory Approval of a Dosing Algorithm of Valganciclovir in Very Young Children.

Population pharmacokinetic (PopPK) and physiologically based pharmacokinetic (PBPK) models are frequently used to support pediatric drug development. Both methods have strengths and limitations and we used them complementarily to support the regulatory approval of a dosing algorithm for valganciclovir (VGCV) in children <4 months old. An existing pediatric PBPK model was extended to neonates and showed that potential physiological differences compared with older children are minor. The PopPK model was used to simulate ganciclovir (GCV) exposures in children with population typical combinations of body size and renal function and to assess the effectiveness of an alternative dosing algorithm suggested by the US Food and Drug Administration. PBPK and PopPK confirmed that the proposed VGCV dosing algorithm achieves similar GCV exposures in children of all ages and that the alternative dosing algorithm leads to underexposure in a substantial fraction of patients. Our approach raised the confidence in the VGCV dosing algorithm for children <4 months old and supported the regulatory approval.

Pulmonary TB bacteriologically confirmed by induced sputum among children at Bugando Medical Centre, Tanzania.

BACKGROUND: The diagnosis of paediatric tuberculosis (TB) remains difficult in resource-: poor settings. OBJECTIVE: To evaluate induced sputum collection and examination using microscopy, culture and Xpert(®) MTB/RIF assay for the diagnosis of pulmonary TB (PTB) in a Tanzanian hospital vs. PTB diagnosis using clinical scoring tools alone. METHODS: We conducted a cross-sectional study from October 2013 to April 2014 at our hospital in northwestern Tanzania. Children presumed to have TB were assessed using four TB score charts and sputum examination. Sputum samples were analyzed using fluorescence microscopy, solid culture and Xpert. The number of cases microbiologically confirmed was compared to the number of TB cases suspected based on TB score charts. RESULTS: A total of 192 patients were enrolled. Sputum specimens were successfully obtained in 187 (97.4%) patients without any major complications. Ten (5.2%) children were confirmed to have PTB by sputum examination. More than half (50-90%) of the confirmed cases were not detected by score charts alone. CONCLUSION: Sputum induction is both safe and feasible in a severely resource-limited hospital, and can lead to microbiological PTB diagnosis that would not be detected by clinical criteria alone.

Stenting of the Cystic Duct in Benign Disease: A Definitive Treatment for the Elderly and Unwell.

PURPOSE: There have been few case reports describing cystic duct stent insertion in the management of acute cholecystitis secondary to benign disease with no case series published to date. We present our series demonstrating the role of cystic duct stents in managing benign gallbladder disease in those patients unfit for surgery. MATERIALS AND METHODS: Thirty three patients unfit for surgery in our institution underwent cystic duct stent insertion for the management of acute cholecystitis in the period June 2008 to June 2013. Patients underwent a mixture of transperitoneal and transhepatic gallbladder puncture. The cystic duct was cannulated with a hydrophilic guidewire which was subsequently passed through the common bile duct and into the duodenum. An 8Fr 12-cm double-pigtail stent was placed with the distal end lying within the duodenum and the proximal end within the gallbladder. RESULTS: Ten patients presented with gallbladder perforation, 21 patients with acute cholecystitis, 1 with acute cholangitis and 1 with necrotising pancreatitis. The technical success rate was 91%. We experienced a 13% complication rate with 3% mortality rate at 30 days. CONCLUSION: Cystic duct stent insertion can be successfully used to manage acute cholecystitis, gallbladder empyema or gallbladder perforations in those unfit for surgery and should be considered alongside external gallbladder drainage as a definitive mid-term treatment option.

Clinical determinants of a positive visual inspection after treatment with acetic acid for cervical cancer screening.

OBJECTIVE: To examine the determinants of a positive visual inspection after acetic acid (VIA), including the relationship of testing positive for high-risk human papillomavirus (HR-HPV), which is the necessary cause of cervical cancer. DESIGN: A prospective cohort study. SETTING: Three clinical sites in rural China. POPULATION: A total of 7541 women aged 25-65 years. METHODS: All women underwent VIA, DNA testing, by two DNA tests performed on both clinician- and self-collected specimens, and HPV E6 oncoprotein testing. Those positive by any test underwent colposcopy and four-quadrant biopsy evaluation. A random sample of women with negative screening results also underwent colposcopy and, if colposcopic abnormalities were observed, four-quadrant biopsy evaluation was performed. Women diagnosed with cervical intraepithelial neoplasia grade 2 (CIN2), or more severe grades (CIN2 + ), underwent treatment. MAIN OUTCOME MEASURE: Testing positive for VIA. RESULTS: Overall, 7.6% (95% confidence interval, 95% CI, 7.0-8.2%) had a positive VIA. Women who tested positive for HPV were more likely to have a positive VIA than women who tested negative for HPV (15.0%, 95% CI 12.9-17.2% versus 6.3%, 95% CI 5.7-6.9%; P < 0.001). Older women were less likely to have a positive VIA (Ptrend  < 0.001), including women with CIN2 +  (Ptrend  < 0.001). A logistic regression model demonstrated that diagnosis (CIN2 +  versus

'Cough-triggered' tuberculosis screening among adults with diabetes in Tanzania.

AIMS: Diabetes increases the risk of tuberculosis and the prevalence of diabetes is rising in tuberculosis-endemic regions such as sub-Saharan Africa. Resource-appropriate strategies for tuberculosis case finding among African adults with diabetes are needed. The aims of this study were to determine prevalence of tuberculosis and evaluate one screening strategy among adult Tanzanians with diabetes. METHODS: In this prospective cohort study, we evaluated a 'cough-triggered' strategy for tuberculosis case finding among adults with diabetes at our zonal hospital in Tanzania. All adults with diabetes and cough underwent further tuberculosis symptom assessment, and those with productive cough had sputum collected for microscopy and Mycobacterium tuberculosis culture. RESULTS: Between September 2011 and March 2012, 700 adults with diabetes attended our hospital. A total of 693 were enrolled, 121/693 (17.5%) had cough and 32/693 (4.6%) had at least two of the classic symptoms of tuberculosis. Of note, 87/121 (71.9%) of patients with cough could not produce sputum spontaneously. Nine patients were diagnosed with tuberculosis for a prevalence of 1299/100 000 (1.3%), sevenfold greater than the national average. CONCLUSIONS: Tuberculosis is common among Tanzanian adults with diabetes, but tuberculosis case finding is challenging because of the high prevalence of non-productive cough. This low-cost, 'cough-triggered' tuberculosis case-finding strategy may serve as a reasonable first step for improving tuberculosis screening among adults with diabetes in sub-Saharan Africa.

The state of hepatitis B and C in the Mediterranean and Balkan countries: report from a summit conference.

The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely unrecognized, including in high-risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.

Predictors of tuberculosis in first 6 months after initiation of antiretroviral therapy: a case-control study.

SETTING: In Africa, 10% of human immunodeficiency virus (HIV) infected adults starting antiretroviral therapy (ART) die within the first year, and tuberculosis (TB) is the leading cause of death. OBJECTIVE: To investigate the predictors of ART-associated TB at an adult HIV clinic in Tanzania. DESIGN: In this nested case-control study, adults starting ART were screened for TB according to the World Health Organization protocol. Those not diagnosed with TB were observed for 6 months. Patients diagnosed with TB were defined as cases, and controls were selected from among the patients who did not develop TB using incidence density matching. RESULTS: Among the 2514 HIV-positive adults in our cohort, 72 (3%) were diagnosed with TB during the first 6 months of ART. By multivariate analysis, baseline characteristics predictive of TB were cough, fever and night sweats; 76% (55/72) of the cases had at least one of these symptoms at the time of starting ART. CONCLUSION: Overall, 75% of the patients who developed TB during the first 6 months of ART had TB symptoms at the time of starting ART. Improved TB diagnostics and/or better strategies for empirical anti-tuberculosis treatment are needed for patients with symptoms of TB at ART initiation.

Collaborative home medicines review delays time to next hospitalization for warfarin associated bleeding in Australian war veterans.

WHAT IS KNOWN AND BACKGROUND: Unintended bleeds are a common complication of warfarin therapy. We aimed to determine the impact of general practitioner-pharmacist collaborative medication reviews in the practice setting on hospitalization-associated bleeds in patients on warfarin. METHOD: We undertook a retrospective cohort study using administrative claims data for the ambulatory veteran and war widow population, Australia. Participants were veterans, war widows and their dependents aged 65 years and over dispensed warfarin. The exposed groups were those exposed to a general practitioner (GP)-pharmacist collaborative home medication review. The service includes GP referral, a home visit by an accredited pharmacist to identify medication-related problems, a pharmacist report with follow-up undertaken by the GP. The outcome measure was time to next hospitalization for bleeding. RESULTS: There were 816 veterans exposed to a home medicines review and 16,320 unexposed patients, with an average age of 81.5 years, and six to seven co-morbidities. Adjusted results showed a 79% reduction in likelihood of hospitalization for bleeding between 2 and 6 months (HR, 0.21 95% CI, 0.05-0.87) amongst those who had received a home medicines reviewed compared to the unexposed patients. No effect was seen in the time period from review to 2 months, nor in the time period 6 to 12 months post a review. WHAT IS NEW AND CONCLUSION: Medicines review in the practice setting delays time to next hospitalization for bleeding in those treated with warfarin in the period 2 to 6 months after the review, but is not sustained over time. Six monthly medication reviews may be required for patients on warfarin who are considered at high risk of bleeding.

Pheromone disruption of Argentine ant trail integrity.

Disruption of Argentine ant trail following and reduced ability to forage (measured by bait location success) was achieved after presentation of an oversupply of trail pheromone, (Z)-9-hexadecenal. Experiments tested single pheromone point sources and dispersion of a formulation in small field plots. Ant walking behavior was recorded and digitized by using video tracking, before and after presentation of trail pheromone. Ants showed changes in three parameters within seconds of treatment: (1) Ants on trails normally showed a unimodal frequency distribution of walking track angles, but this pattern disappeared after presentation of the trail pheromone; (2) ants showed initial high trail integrity on a range of untreated substrates from painted walls to wooden or concrete floors, but this was significantly reduced following presentation of a point source of pheromone; (3) the number of ants in the pheromone-treated area increased over time, as recruitment apparently exceeded departures. To test trail disruption in small outdoor plots, the trail pheromone was formulated with carnuba wax-coated quartz laboratory sand (1 g quartz sand/0.2 g wax/1 mg pheromone). The pheromone formulation, with a half-life of 30 h, was applied by rotary spreader at four rates (0, 2.5, 7.5, and 25 mg pheromone/m(2)) to 1- and 4-m(2) plots in Volcanoes National Park, Hawaii. Ant counts at bait cards in treated plots were significantly reduced compared to controls on the day of treatment, and there was a significant reduction in ant foraging for 2 days. These results show that trail pheromone disruption of Argentine ants is possible, but a much more durable formulation is needed before nest-level impacts can be expected.

Polypharmacy management among Australian veterans: improving prescribing through the Australian Department of Veterans' Affairs' prescriber feedback programme.

BACKGROUND: Older patients are potentially at risk from the effects of polypharmacy (PP) and/or drug-drug interactions. AIMS: To examine the effects of a targeted patient-specific prescriber feedback programme on patients prescribed more than 19 individual medications over the 3-month study period. METHODS: The Commonwealth Department of Veterans' Affairs commissioned a review of Repatriation Pharmaceutical Benefit Scheme claims data to identify patients potentially at risk of drug injury through either PP (> or =20 unique medications during 3 months) or clinically significant drug interactions (DI). Dispensing information for the patient at risk, relevant clinical guidelines and a personalized covering letter were mailed to the main prescribing general practitioner of the identified veteran patient. The claims data were then re-analysed after the programme. RESULTS: There was a significant reduction in the mean number of unique medications prescribed over a 3-month period 1 year after the prescriber feedback (mean change = -2.22; 95% confidence interval -3.54 to -0.90; P = 0.0013) for patients identified with ongoing PP. There was also a significant reduction in the number of DI pairs (mean change = -0.73; 95% confidence interval -0.77 to -0.69; P < 0.0001) for the patients identified with an ongoing DI. The number of patients dispensed one or more DI pairs decreased from 836 to 318 after the feedback. CONCLUSION: A targeted prescriber feedback programme can influence general practitioner prescribing at an individual patient level and, therefore, contribute to the quality use of medicines.

Intraocular pressure alterations following intravitreal triamcinolone acetonide.

AIMS: To determine the prevalence of intraocular pressure (IOP) alterations following intravitreal injection of triamcinolone acetonide (IVTA) and to assess possible risk factors of IOP elevation in eyes receiving single and/or repeat injections. METHODS: Retrospective, consecutive case series. 570 consecutive eyes of 536 patients who received a single IVTA injection (4 mg/0.1 ml) and a second set of 43 eyes of 40 patients who received a second injection. Retrospective review of all IVTA cases performed by three vitreoretinal surgeons over a 42 month period beginning in 2000. The main outcome measure was change in IOP defined as absolute value of IOP elevation (5 mm Hg or higher, 10 mm Hg or higher), and percentage of baseline (30% or higher increase from baseline IOP). RESULTS: Of the 528 eyes receiving single injections, 281 (53.2%) had an IOP elevation; 267 eyes (50.6%) experienced an elevation of IOP of at least 30%, and 245 (45.8%) and 75 (14.2%) eyes had an increase of 5 mm Hg or 10 mm Hg or more, respectively. Baseline IOP greater than 16 mm Hg is a risk factor for post-injection IOP elevation. Of the 43 eyes which received a second injection, 28 (65.1%) experienced an increase in IOP of at least 30% of baseline. Filtering surgery was required in five (0.094%) of the single and one (2.3%) of repeat injection eyes. CONCLUSIONS: Elevated IOP after IVTA is common and patients should be monitored beyond 6 months post-injection. Patients with a baseline IOP more than 16 mm Hg or receiving a second injection should be carefully monitored for an elevated IOP.

Motifs that mediate dendritic targeting in hippocampal neurons: a comparison with basolateral targeting signals.

One model for dendritic protein sorting in neurons is based on parallels with basolateral targeting in Madin-Darby Canine Kidney (MDCK) epithelial cells. The goal of this study was to further evaluate this model by analyzing the neuronal targeting of several proteins that contain well-defined basolateral sorting motifs. When we expressed FcRgammaII-B2 and CD44, two basolateral markers whose sorting depends on dihydrophobic motifs, they were unpolarized in hippocampal neurons. We also assessed the localization of the Epidermal Growth Factor Receptor (EGFR), a basolateral protein whose sorting signal contains a proline-rich motif and two dihydrophobic motifs. EGFR was restricted to the dendrites in neurons and relied on the same sorting signal for proper targeting. These results show that the dendritic sorting machinery in neurons does not recognize dihydrophobic-based basolateral sorting signals. In contrast, the sorting signal present in EGFR directs both basolateral and dendritic targeting and defines a novel dendritic targeting motif.