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More efficacious treatment regimens are needed for tuberculosis, however, drug development is impeded by a lack of reliable biomarkers of disease severity and of treatment effect. We conducted a directed screen of host biomarkers in participants enrolled in a tuberculosis clinical trial to address this need. Serum samples from 319 protocol-correct, culture-confirmed pulmonary tuberculosis patients treated under direct observation as part of an international, phase 2 trial were screened for 70 markers of infection, inflammation, and metabolism. Biomarker assays were specifically developed for this study and quantified using a novel, multiplexed electrochemiluminescence assay. We evaluated the association of biomarkers with baseline characteristics, as well as with detailed microbiologic data, using Bonferroni-adjusted, linear regression models. Across numerous analyses, seven proteins, SAA1, PCT, IL-1β, IL-6, CRP, PTX-3 and MMP-8, showed recurring strong associations with markers of baseline disease severity, smear grade and cavitation; were strongly modulated by tuberculosis treatment; and had responses that were greater for patients who culture-converted at 8weeks. With treatment, all proteins decreased, except for osteocalcin, MCP-1 and MCP-4, which significantly increased. Several previously reported putative tuberculosis-associated biomarkers (HOMX1, neopterin, and cathelicidin) were not significantly associated with treatment response. In conclusion, across a geographically diverse and large population of tuberculosis patients enrolled in a clinical trial, several previously reported putative biomarkers were not significantly associated with treatment response, however, seven proteins had recurring strong associations with baseline radiographic and microbiologic measures of disease severity, as well as with early treatment response, deserving additional study.

More efficacious treatment regimens are needed for tuberculosis, however, drug development is impeded by a lack of reliable biomarkers of disease severity and of treatment effect. We conducted a directed screen of host biomarkers in participants enrolled in a tuberculosis clinical trial to address this need. Serum samples from 319 protocol-correct, culture-confirmed pulmonary tuberculosis patients treated under direct observation as part of an international, phase 2 trial were screened for 70 markers of infection, inflammation, and metabolism. Biomarker assays were specifically developed for this study and quantified using a novel, multiplexed electrochemiluminescence assay. We evaluated the association of biomarkers with baseline characteristics, as well as with detailed microbiologic data, using Bonferroni-adjusted, linear regression models. Across numerous analyses, seven proteins, SAA1, PCT, IL-1β, IL-6, CRP, PTX-3 and MMP-8, showed recurring strong associations with markers of baseline disease severity, smear grade and cavitation; were strongly modulated by tuberculosis treatment; and had responses that were greater for patients who culture-converted at 8weeks. With treatment, all proteins decreased, except for osteocalcin, MCP-1 and MCP-4, which significantly increased. Several previously reported putative tuberculosis-associated biomarkers (HOMX1, neopterin, and cathelicidin) were not significantly associated with treatment response. In conclusion, across a geographically diverse and large population of tuberculosis patients enrolled in a clinical trial, several previously reported putative biomarkers were not significantly associated with treatment response, however, seven proteins had recurring strong associations with baseline radiographic and microbiologic measures of disease severity, as well as with early treatment response, deserving additional study.

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The diopter power and magnification matrices characterize the first-order properties of ophthalmic lenses for different gaze directions. Therefore an efficient method to compute them is highly valuable in ophthalmic lens design and optical performance simulations. I present a novel method to numerically compute these matrices in ophthalmic lenses comprising any set of arbitrary surfaces. The method is based on computing one base ray, along the gaze direction, and two rays close to it. These two rays are obtained varying a small parameter that indicates their separation from the base ray. The method was validated comparing the results with a single refractive surface where exact solutions are directly obtained.

Objective: This study evaluated the effects of advanced footwear technology (AFT) spikes on running performance measures, spatiotemporal variables, and perceptive parameters on different surfaces (track and grass). Methods: Twenty-seven male trained runners were recruited for this study. In Experiment 1, participants performed 12 × 200 m at a self-perceived 3000 m running pace with a recovery of 5 min. Performance (time in each repetition), spatiotemporal, and perceptive parameters were measured. In Experiment 2, participants performed 8 × 5 min at 4.44 m/s while energy cost of running (W/kg), spatiotemporal, and perceptive parameters were measured. In both experiments the surface was randomized and mirror order between spike conditions (Polyether Block Amide (PEBA) and PEBA + Plate) was used. Results: Experiment 1: Runners were faster on the track ( p = 0.002) and using PEBA + Plate spike ( p = 0.049). Experiment 2: Running on grass increased energy cost ( p = 0.03) and heart rate ( p < 0.001) regardless of the spike used, while PEBA + Plate spike reduced respiratory exchange ratio (RER) ( p = 0.041). Step frequency was different across surfaces ( p < 0.001) and spikes ( p = 0.002), with increased performance and comfort perceived with PEBA + Plate spikes ( p < 0.001; p = 0.049). Conclusions: Running on the track surface with PEBA + Plate spikes enhanced auto-perceived 3000 m running performance, showed lower RER, and improved auto-perceptive comfort and performance. Running on grass surfaces increased energy cost and heart rate without differences between spike conditions.

Introduction/purpose: Previous results about shoe longitudinal bending stiffness (LBS) and running economy (RE) show high variability. This study aimed to assess the effects of shoes with increased LBS on RE and performance in trained and national runners., Methods: Twenty-eight male runners were divided into two groups according to their 10-km performance times (trained, 38-45 min and national runners, <34 min). Subjects ran 2 × 3 min (at 9 and 13 km·h -1 for trained, and 13 and 17 km·h -1 for national runners) with an experimental shoe with carbon fiber plate to increase the LBS (Increased LBS) and a control shoe (without carbon fiber plate). We measured energy cost of running (W·kg -1 ) and spatiotemporal parameters in visit one and participants performed a 3000 m time trial (TT) in two successive visits., Results: Increased LBS improved RE in the trained group at slow (11.41 ± 0.93 W·kg -1 vs 11.86 ± 0.93 W·kg -1 ) and fast velocity (15.89 ± 1.24 W·kg -1 vs 16.39 ± 1.24 W·kg -1 ) and only at the fast velocity in the national group (20.35 ± 1.45 W·kg -1 vs 20.78 ± 1.18 W·kg -1 ). The improvements in RE were accompanied by different changes in biomechanical variables between groups. There were a similar improvement in the 3000 m TT test in Increased LBS for trained (639 ± 59 vs 644 ± 61 s in control shoes) and national runners (569 ± 21 vs 574 ± 21 s in control shoes) with more constant pace in increased LBS compared with control shoes in both groups., Conclusions: Increasing shoe LBS improved RE at slow and fast velocities in trained runners and only at fast velocity in national runners. However, the 3000 m TT test improved similarly in both levels of runners with increased LBS. The improvements in RE are accompanied by small modifications in running kinematics that could explain the difference between the different levels of runners., (Copyright © 2023 by the American College of Sports Medicine.)

Background: During the COVID-19 pandemic, the paediatric population plays a minor role in the spread of the SARS-CoV-2 virus. However, in order to keep schools open and reduce SARS-CoV spreading, it is necessary to identify and isolate early SARS-CoV-2 positive paediatric patients even if they are asymptomatic. The aim of this study was to describe a setting for SARS-CoV 2 testing based on the spontaneous presentation of paediatric patients attending school without a medical prescription and explore its appropriateness., Study Design: Cross-sectional study., Methods: The study performed between September 2020 and March 2021 among a sample of 13,283 paediatric patients who underwent a swab in four different hospital settings (school hot spot, emergency department, day hospital setting and hospital wards). For each patients we collected: date of swab execution, type of swab, execution setting of the swab, result of the swab, information about community spread of the virus in the 14 days prior to the swab execution, sex and age., Results: In our sample, females accounted for 45.8%. The median age was 6.8 years (IQR 3.0-11.2) and the most frequent age category was between 6 and 11 years (27.9%). At multivariable models with a swab tested positive as outcome. The swabs executed in all the hospital settings had a lower likelihood of resulting positive compared with the school hot spot setting. Compared with adolescents aged between 14 and 19 years old, new-borns below 3 months (adjOR 1.83, 95% C.I. 1.14-3) and patients aged between 11 and 14 years old (adjOR 1.32, 95% C.I. 1.07-1.63) reported a higher probability of a swab tested positive. Instead, children aged between 3 months and 3 years (adjOR 0.77, 95% C.I. 0.61-0.96) and children aged between 3 years and 6 years (adjOR 0.66, 95% C.I. 0.53-0.83) were less likely to result positive. The higher was the mean of pooled Rt in the 14 days preceding the swab, the higher was the likelihood of resulting positive (adjOR 1.75, 95% C.I. 1.53-1.99)., Conclusion: In conclusion, we found a high incidence of paediatric patients positive to the test for the detection of SARS-CoV-2 at the school hot spot compared with other settings during the period of observation. The free access modality to the nasopharyngeal swab was effective in identifying patients with COVID-19. Public health authorities should implement these testing modality in order to help reduce the spread of SARS-CoV-2 in school settings.

Introduction and Objectives: there is insufficient data regarding bacterial infections in patients with cirrhosis to support recommendations for empiric antibiotic treatments, particularly in Latin America. This study aimed to evaluate bacterial infection's clinical impact and microbiological characteristics, intending to serve as a platform to revise current practices., Materials and Methods: multicenter prospective cohort study of patients with cirrhosis and bacterial infections from Argentina and Uruguay. Patient and infection-related information were collected, focusing on microbiology, antibiotic susceptibility patterns, and outcomes., Results: 472 patients were included. Spontaneous bacterial infections and urinary tract infections (UTIs) were registered in 187 (39.6%) and 116 (24.6%) patients, respectively, representing the most common infections. Of the 256 culture-positive infections, 103 (40.2%) were caused by multidrug-resistant organisms (reaching 50% for UTI), and 181 (70.7%) received adequate initial antibiotic treatment. The coverage of cefepime and ceftriaxone was over 70% for the empirical treatment of community-acquired spontaneous infections, but ceftazidime´s coverage was only 40%. For all UTI cases and for healthcare-associated or nosocomial spontaneous bacterial infections, the lower-spectrum antibiotics that covered at least 70% of the isolations were imipenem and meropenem. During hospitalization, a second bacterial infection was diagnosed in 9.8% of patients, 23.9% required at least one organ support, and 19.5% died., Conclusions: short-term mortality of bacterial infections in patients with cirrhosis is very high, and a high percentage were caused by multidrug-resistant organisms, particularly in UTIs. The information provided might serve to adapt recommendations, particularly related to empirical antibiotic treatment in Argentina and Uruguay. The study was registered in Clinical Trials (NCT03919032)., Competing Interests: Declaration of Competing Interests None., (Copyright © 2023 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

The aim of this study was to analyze the acute effects of high vs low-intensity cycling efforts, combined with plyometrics, on vertical jump performance. Twenty-four physically active men (mean ± SD: 23 ± 2 years, 72.1 ± 10.1 kg, 1.73 ± 0.07 m) were randomly divided into two groups: experimental group (EXP, n = 16) and control group (CON, n = 8). EXP competed 2 experimental trials in a random order: (a) short high-intensity interval exercise (HI + Plyo) [5 × 10 s of cycling ("all-out")/50 s active rest] or (b) low-intensity continuous exercise (LO + Plyo) [5 min of cycling at 75% of the HR max )], along with 3 × 10 plyometric bounds (drop jumps)/1 min rest between sets. CON used a preconditioning activity of 13 min of low intensity cycling at ~60% of HR max . Both EXP interventions significantly increased (p ≤ 0.05) the countermovement jump (CMJ) height at 1 min, 3 min, 6 min and 9 min compared to baseline, while the CON remained unchanged. There were no significant differences in CMJ performance enhancement between HI + Plyo (largest 11.2% at 9 min) and LO + Plyo (largest 15.0% at 3 min) at any time-point, suggesting that the plyometric component may be most important, with HR recovery taking slightly longer following HI + Plyo. The findings suggest that CMJ performance can be enhanced following high or low-intensity cycling combined with plyometric preconditioning activities in active males, the optimum recovery period likely to be individual-specific., Competing Interests: The authors declare no conflict of interest., (Copyright © Biology of Sport 2023.)

There is a trend in optical system design toward explicitly considering real-world industrial demands in the metrics to be optimized, from which emerges a cost-performance trade-off. Another relevant recent tendency is the so-called end-to-end design, where the design metric is an expected quality index of the final image, after digital restoration. We propose an integrated approach for analyzing the cost-performance trade-off in end-to-end designs. We exemplify it with a simple optical model where the cost is determined by the inclusion of an aspherical surface. We show that the resulting optimal trade-off configurations when applying an end-to-end design are substantially different from a conventional design. Such differences, as well as the increase in performance, are especially significant for lower-cost configurations.

Women are underrepresented in STEM fields across the world. We investigate a perceptual mechanism that may contribute to this gender disparity beginning in early childhood. We explore how visual information about the gender composition of a group of scientists impacts children's persistence on a STEM task and their evaluations of group members. One hundred sixty-six 4- to 6-year-old children viewed one of four groups of scientists: all-male, all-female, a lone female among all-males, or a lone male among all-females. Whereas children's persistence on a STEM task did not change across conditions, their trait judgments did. Children judged the all-male and all-female group scientists as "hardworking," but judged the lone female scientist as "smart." However, they were as likely to judge the lone male scientist as "smart" as to judge him "hardworking." The role of group visualization as a learning mechanism impacting children's perceptions of scientists as early as the preschool years is discussed., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Multifocal and/or extended depth-of-focus designs are widely used in many optical applications. In most of them, the optical configuration has axial symmetry. A usual design strategy consists of exploring the optimal wavefronts that emerging out of the optical system would provide the desired multifocal properties. Those properties are closely related to light concentration on caustic surfaces. We present a systematic analysis of how to obtain those multifocal wavefronts given some prescriptions on the locations of caustics. In particular, we derive several multifocal wavefronts under archetypical prescriptions in the sagittal caustic alone, or combined with the tangential one at certain points, with some emphasis on visual optics applications.