Evidence of successful management of multidrug-resistant tuberculosis (MDRTB) is mainly generated from referral hospitals in high-income countries. We evaluate the management of MDRTB in 5 ...resource-limited countries: Estonia, Latvia, Peru, the Philippines, and the Russian Federation. All projects were approved by the Green Light Committee for access to quality-assured second-line drugs provided at reduced price for MDRTB management. Of 1047 MDRTB patients evaluated, 119 (11%) were new, and 928 (89%) had received treatment previously. More than 50% of previously treated patients had received both first- and second-line drugs, and 65% of all patients had infections that were resistant to both first- and second-line drugs. Treatment was successful in 70% of all patients, but success rate was higher among new (77%) than among previously treated patients (69%). In resource-limited settings, treatment of MDRTB provided through, or in collaboration with, national TB programs can yield results similar to those from wealthier settings.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The five-target '25×25' strategy for tackling the emerging global epidemic of non-communicable diseases (NCDs) focuses on four diseases (CVD, diabetes, cancer, and chronic respiratory disease), four ...risk factors (tobacco, diet and physical activity, dietary salt, and alcohol), and one cardiovascular preventive drug treatment. The goal is to decrease mortality from NCDs by 25 per cent by the year 2025. The 'standard approach' to the '25×25' strategy has the benefit of simplicity, but also has major weaknesses. These include lack of recognition of: (i) the fundamental drivers of the NCD epidemic; (ii) the 'missing NCDs', which are major causes of morbidity; (iii) the 'missing causes' and the 'causes of the causes'; and (iv) the role of health care and the need for integration of interventions.
This study addresses deflagration initiation of lean and stoichiometric hydrogen–air mixtures by the sudden discharge of a hot jet of their adiabatic combustion products. The objective is to compute ...the minimum jet radius required for ignition, a relevant quantity of interest for safety and technological applications. For sufficiently small discharge velocities, the numerical solution of the problem requires integration of the axisymmetric Navier–Stokes equations for chemically reacting ideal-gas mixtures, supplemented by standard descriptions of the molecular transport terms and a suitably reduced chemical-kinetic mechanism for the chemistry description. The computations provide the variation of the critical radius for hot-jet ignition with both the jet velocity and the equivalence ratio of the mixture, giving values that vary between a few tens microns to a few hundred microns in the range of conditions explored. For a given equivalence ratio, the critical radius is found to increase with increasing injection velocities, although the increase is only moderately large. On the other hand, for a given injection velocity, the smallest critical radius is found at stoichiometric conditions.
► Deflagration initiation of H2–air mixtures by hot jets is addressed numerically. ► Computed critical radii for ignition at ambient p and T are presented. ► The critical radius depends on mixture equivalence ratio and jet discharge velocity. ► The equivalence ratio is the most influencing parameter. ► The smallest critical radius is found at stoichiometric conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This computational study addresses deflagration initiation of lean, stoichiometric, and moderately rich hydrogen–air mixtures by the sudden discharge of a hot planar jet of its adiabatic combustion ...products. The objective is to determine the minimum slot size required for ignition, a relevant quantity of interest for safety and technological applications concerning the accidental ignition of hydrogen. For sufficiently small jet velocities, the numerical solution of the problem requires integration of the two-dimensional Navier–Stokes equations for chemically reacting ideal-gas mixtures, supplemented by standard descriptions of the molecular transport terms and a reduced chemical–kinetic mechanism suitable for hydrogen–air combustion. The computations provide the variation of the critical slot size for hot-jet ignition with both the jet Reynolds number and the equivalence ratio of the mixture. In particular, it is seen that, while the Reynolds number exerts only a relatively weak effect on the ignition process, the influence of the equivalence ratio is much more pronounced, with the smallest slot widths found for stoichiometric or slightly-rich conditions. The numerical results show three different ignition modes, with the flame developing from a clearly identified ignition kernel located either at the core of the leading vortex pair (mode 1), at the symmetry plane near the leading edge of the starting jet (mode 2), or at the jet stem connecting the jet exit with the starting vortex (mode 3).
•Deflagration initiation of H2-air mixtures by planar hot jets is addressed numerically.•Computed critical slot sizes for ignition at ambient p and T are presented.•The critical slot size depends on jet Reynolds number and on mixture equivalence ratio.•Smaller critical slot sizes are found at near-stoichiometric conditions.•Computations show mild effects of thermal diffusion and non-impulsive jet discharge.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Optical Coherence Tomography (OCT) is the major diagnostic tool for the leading cause of blindness in developed countries: Diabetic Macular Edema (DME). Depending on the type of fluid accumulations, ...different treatments are needed. In particular, Cystoid Macular Edemas (CMEs) represent the most severe scenario, while Diffuse Retinal Thickening (DRT) is an early indicator of the disease but a challenging scenario to detect. While methodologies exist, their explanatory power is limited to the input sample itself. However, due to the complexity of these accumulations, this may not be enough for a clinician to assess the validity of the classification. Thus, in this work, we propose a novel approach based on multi-prototype networks with vision transformers to obtain an example-based explainable classification. Our proposal achieved robust results in two representative OCT devices, with a mean accuracy of 0.9099 ± 0.0083 and 0.8582 ± 0.0126 for CME and DRT-type fluid accumulations, respectively.
No consensus exists on how to average data to optimize
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assessment. Although the
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value is reduced with larger averaging blocks, no mathematical procedure is available to account for the effect of ...the length of the averaging block on
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AIMS: To determine the effect that the number of breaths or seconds included in the averaging block has on the
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value and its reproducibility and to develop correction equations to standardize
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values obtained with different averaging strategies.
Eighty-four subjects performed duplicate incremental tests to exhaustion (IE) in the cycle ergometer and/or treadmill using two metabolic carts (Vyntus and Vmax N29). Rolling breath averages and fixed time averages were calculated from breath-by-breath data from 6 to 60 breaths or seconds.
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decayed from 6 to 60 breath averages by 10% in low fit (
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< 40 mL kg
min
) and 6.7% in trained subjects. The
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averaged from a similar number of breaths or seconds was highly concordant (CCC > 0.97). There was a linear-log relationship between the number of breaths or seconds in the averaging block and
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(R
> 0.99, P < 0.001), and specific equations were developed to standardize
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values to a fixed number of breaths or seconds. Reproducibility was higher in trained than low-fit subjects and not influenced by the averaging strategy, exercise mode, maximal respiratory rate, or IE protocol.
The
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decreases following a linear-log function with the number of breaths or seconds included in the averaging block and can be corrected with specific equations as those developed here.
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BFBNIB, FSPLJ, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Patients with compensated cirrhosis with clinically significant portal hypertension (CSPH: HVPG > 10 mm Hg) have a high risk of decompensation. HVPG is, however, an invasive procedure not available ...in all centers. The present study aims to assess whether metabolomics can improve the capacity of clinical models in predicting clinical outcomes in these compensated patients.
This is a nested study from the PREDESCI cohort (an RCT of nonselective beta-blockers vs. placebo in 201 patients with compensated cirrhosis and CSPH), including 167 patients for whom a blood sample was collected. A targeted metabolomic serum analysis, using ultra-high-performance liquid chromatography-mass spectrometry, was performed. Metabolites underwent univariate time-to-event cox regression analysis. Top-ranked metabolites were selected using Log-Rank p -value to generate a stepwise cox model. Comparison between models was done using DeLong test. Eighty-two patients with CSPH were randomized to nonselective beta-blockers and 85 to placebo. Thirty-three patients developed the main endpoint (decompensation/liver-related death). The model, including HVPG, Child-Pugh, and treatment received ( HVPG/Clinical model ), had a C-index of 0.748 (CI95% 0.664-0.827). The addition of 2 metabolites, ceramide (d18:1/22:0) and methionine (HVPG/Clinical/Metabolite model), significantly improved the model's performance C-index of 0.808 (CI95% 0.735-0.882); p =0.032. The combination of these 2 metabolites together with Child-Pugh and the type of treatment received (Clinical/Metabolite model) had a C-index of 0.785 (CI95% 0.710-0.860), not significantly different from the HVPG-based models including or not metabolites.
In patients with compensated cirrhosis and CSPH, metabolomics improves the capacity of clinical models and achieves similar predictive capacity than models including HVPG.
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BFBNIB, FZAB, GIS, IJS, KILJ, OILJ, SBCE, SBMB, UL, UPUK
Paracetamol is the one of the most commonly used medications during pregnancy. However, its potential antiandrogenic effect has been suggested. The objective of this study was to evaluate ...associations between maternal paracetamol use during pregnancy and anogenital distance (AGD) in male newborns from a Spanish birth cohort. The study included two hundred and seventy-seven mother-male child pairs with self-reported paracetamol use and frequency during each trimester of pregnancy. AGD measurements were taken employing standardized methods. The associations between maternal paracetamol use and AGD measures were evaluated using linear regression models, adjusting for potential confounders and covariates. Overall, 61.7% of pregnant women consumed paracetamol at any time of pregnancy with an average of 9.43 (SD = 15.33) days throughout pregnancy. No associations between the maternal use of paracetamol or its frequency and AGD measures among different trimesters or during the whole pregnancy were found in the adjusted final models. A non-differential misclassification error may have occurred—the recall of paracetamol intake independent of AGD measurements—introducing bias towards the null hypothesis. Nevertheless, the current evidence suggests that paracetamol might have a potential antiandrogenic effect especially in the early stages of fetal development. Thus, it would be highly recommendable to pursue further studies to elucidate the potential effects of paracetamol in human perinatal health and its use among pregnant women.
Bacterial resistance has risen as an important health problem with impact on the pharmaceutical industry because many antibiotics have become ineffective, which has affected their commercialization. ...The Brazilian biodiversity is marked by a vast variety of natural products with significant therapeutic potential, which could bring new perspectives in the treatment of infections caused by resistant microorganisms. The present study aimed to evaluate the antibacterial effect of the essential oil obtained from Eugenia jambolana (EjEO) using the method of microdilution method to determine the Minimum Inhibitory Concentration (MIC). The modulatory effect of this oil on antibiotic activity was determined using both the broth microdilution and gaseous contact methods. The antibacterial effect of the association of the gaseous contact and the use of a LED unit with red and blue lights was also determined. The chemical components of the EjEO were characterized by HPLC, which revealed the presence of α-pinene as a major constituent. The EjEO presented a MIC≥128μg/mL against S. aureus and ≥1024μg/mL against E. coli. The combination of the EjEO with antibiotics presented synergism against E. coli and antagonism against S. aureus. An antagonistic effect was obtained from the association of EjEO with amikacin and erythromycin by the method of gaseous contact. On the other hand, the association of EjEO with ciprofloxacin presented a synergistic effect against S. aureus and E. coli exposed to LED lights. A similar effect was observed in the association of the EjEO with norfloxacin presented synergism against S. aureus in the same conditions. In conclusion, our results demonstrated that the essential oil obtained from Eugenia jambolana interfere with the action of antibiotics against bacteria exposed to LED lights. Thus, further researches are required to elucidate the mechanisms underlying these effects, which could open new perspectives in the development of new antibacterial therapies.
•The Eugenia jambolana essential oil affect the antibiotic activity.•The LED lights interfere with the action of antibiotic activity.•These effects are not observed when the antibiotics were associated with the oil and the LED lights in the same time.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This study aimed to assess the time course of circulating neutrophil and lymphocyte counts and their ratio (NLR) in ST-segment elevation myocardial infarction (STEMI) and coronavirus disease ...(COVID)-19 and explore their associations with clinical events and structural damage. Circulating neutrophil, lymphocyte and NLR were sequentially measured in 659 patients admitted for STEMI and in 103 COVID-19 patients. The dynamics detected in STEMI (within a few hours) were replicated in COVID-19 (within a few days). In both entities patients with events and with severe structural damage displayed higher neutrophil and lower lymphocyte counts. In both scenarios, higher maximum neutrophil and lower minimum lymphocyte counts were associated with more events and more severe organ damage. NLR was higher in STEMI and COVID-19 patients with the worst clinical and structural outcomes. A canonical deregulation of the immune response occurs in STEMI and COVID-19 patients. Boosted circulating innate (neutrophilia) and depressed circulating adaptive immunity (lymphopenia) is associated with more events and severe organ damage. A greater understanding of these critical illnesses is pivotal to explore novel alternative therapies.
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