Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. Objectives: This study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort. Methods: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. Measurements and Main Results: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). Conclusions: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB

Psychological determinants of whole-body endurance performance

Background: No literature reviews have systematically identified and evaluated research on the psychological determinants of endurance performance, and sport psychology performance-enhancement guidelines for endurance sports are not founded on a systematic appraisal of endurance-specific research. Objective: A systematic literature review was conducted to identify practical psychological interventions that improve endurance performance and to identify additional psychological factors that affect endurance performance. Additional objectives were to evaluate the research practices of included studies, to suggest theoretical and applied implications, and to guide future research. Methods: Electronic databases, forward-citation searches, and manual searches of reference lists were used to locate relevant studies. Peer-reviewed studies were included when they chose an experimental or quasi-experimental research design, a psychological manipulation, endurance performance as the dependent variable, and athletes or physically-active, healthy adults as participants. Results: Consistent support was found for using imagery, self-talk, and goal setting to improve endurance performance, but it is unclear whether learning multiple psychological skills is more beneficial than learning one psychological skill. The results also demonstrated that mental fatigue undermines endurance performance, and verbal encouragement and head-to-head competition can have a beneficial effect. Interventions that influenced perception of effort consistently affected endurance performance. Conclusions: Psychological skills training could benefit an endurance athlete. Researchers are encouraged to compare different practical psychological interventions, to examine the effects of these interventions for athletes in competition, and to include a placebo control condition or an alternative control treatment. Researchers are also encouraged to explore additional psychological factors that could have a negative effect on endurance performance. Future research should include psychological mediating variables and moderating variables. Implications for theoretical explanations of endurance performance and evidence-based practice are described

The effect of salts on the mobility and shapes of mudflows in low pressure environments

Introduction Mud volcanism is a widely distributed geological phenomenon on Earth1. Likewise, it has been suggested that mud volcanoes might exist on some other solid-surface bodies in the Solar System, such as Mars2 and the dwarf planet, Ceres3. Since this phenomenon requires liquid water, extraterrestrial mud-volcano-like (MVL) structures represent key targets for studying the hydrology and potential habitability of subsurface environments on other planetary bodies. Thus, identifying the potential morphological signatures of these landforms beyond Earth is an important step in understanding the nature of aqueous environments within the Solar System. Previously performed low-pressure experiments have shown that in case of “cold” surfaces (-15 °C), low viscosity mud propagates similarly to pahoehoe lava types on Earth4, while in case of “warm” (+20 °C) and unconsolidated surfaces, mud “levitates'' and hence can be transported to longer distances5. The effect of composition, however, was not further tested nor discussed. We hypothesize that the potential muds on Mars or other planetary bodies may naturally contain a certain amount of salts which can affect their antifreezing and rheological properties. Therefore we address the question how the salt component in muds may affect their propagation over cold surface in reduced atmospheric pressures, namely those valid for recent Mars. Methods To test our hypothesis, we carried out 54 experiments by experimental procedure adapting the settings (Fig. 1) established for mud flow experiments performed in the Large Mars Vacuum Chamber at the Open University, UK by4,5. During the experiments, portions of mud were released onto a pre-cooled sand surface when the desired pressure (5.9±1 mbar) was reached. The mud was composed of D.I. water, bentonite and with various concentrations (0.5-10%) of salts, namely NaCl, MgSO4 (epsomite), Na2SO4 and CaSO4 were tested. Experiment progress was recorded by cameras situated at the top and sides of the sandbox and temperatures of sand and mud reservoir were measured by thermocouples. In complementary methods, we investigated the pressure-drop-induced evaporative cooling of the brine component on isolated samples in low pressure. Further, we calculated theoretical p-T paths by thermodynamic modeling and measured rheological properties of salty muds for reference Earth atmospheric pressure. Results and discussion Our experiments confirmed expected contrasting behavior of salty mud in decreased pressure (Fig. 2). Individual flows are characterized by unique spatial dispersion and morphological patterns for mutually comparative salt content. Results also revealed thresholds when different muds produce similar patterns and spreading style for highly different concentrations. Performed brine evaporative-cooling experiments showed that the maximum antifreeze potential has NaCl and therefore solutions with this salt are capable of sustaining their liquid state in much smaller pressures than those with other tested salts. The rheological measurements, on the other hand, revealed a contrasting impact of salt addition to viscosity drop of mud samples until these are supersaturated by salt (typically >5-10% concentration in dependence on salt type) and viscosity is further increased. Due to the synergistic effect of decreased viscosity (Fig. 3a) and anti-freezing effect (Fig. 3b) flows are spatially longest for various salts and, not necessarily directly proportional, to their concentrations. For example, 2.5% NaCl mud has a higher anti-freezing effect and lower viscosity compared to 10% MgSO4 (epsomite), resulting in long and narrow flows (Fig. 3c). The increased viscosity of MgSO4 effectively slows the flow, supports the formation of a protective crust and the development of serial, long lobes that maintain liquid mud in their interiors (Fig. 2b,3c). Both salts then exhibit similar spatial dispersion but entirely different styles of propagation and surface geometric pattern. These results are contrasting to previously published experiments and reveal that the increased content of salts leads to different regimes of mud propagation, not necessarily similar to pahoehoe lavas. All these findings therefore suggest that the salt type and concentrations dissolved within the muddy mixture are important factors in controlling the ultimate shapes, textures and dynamics of mud flows emplaced e.g. on Mars or on other bodies with a thin or non-existent atmosphere. Higher salinity levels extend the unfrozen state and promote the wider spatial dispersion of muds until they reach a certain point of saturation with salts. All this suggests that on Mars, contrary to Earth, salts can play an important role in shaping MVL structures. Variations in salt types and concentrations might help to, at least partly, explain the large variability in the shapes of these hypothesized martian MVL structures

The within-participant correlation between perception of effort and heart rate-based estimations of training load in elite soccer players.

The measurement of relative physiological stress during training is important because this is the stimulus for the long-term adaptive response. Measurements of perceived exertion (RPE) have been reported to correlate with the heart rate during field-based training sessions. Nevertheless, there are few studies on how well RPE tracks with the heart rate over repeated training sessions in elite soccer players. Therefore, we aimed to quantify the within-participant correlations between variability in session-RPE (sRPE) and the heart rate in elite male soccer players, and to determine whether the playing position moderated these correlations. The field-based training of four central defenders, four wide defenders, six central midfielders, two wide midfielders and three attackers from an elite English Premier League squad were monitored over an entire in-season competitive period, giving a total of 1010 individual training sessions for study. Correlations between session-RPE and heart rates were quantified using a within-participant model. The correlation between changes in sRPE and heart rates was r = 0.75 (95% CI: 0.71-0.78). This correlation remained high across the various player positions (wide-defender, r = 0.81; central-defender, r = 0.74; wide midfielder, r = 0.70; central midfielder, r = 0.70; attacker, r = 0.84; P < 0.001). The correlation between changes in RPE and heart rates, measured during a season-long period of field-based training, is high in a sample of elite soccer players

Vernonia cinerea Less. supplementation and strenuous exercise reduce smoking rate: relation to oxidative stress status and beta-endorphin release in active smokers

<p>Abstract</p> <p>Purpose</p> <p>The aim of this study was to evaluate the effects of <it>Vernonia cinerea </it>Less. (VC) supplementation and exercise on oxidative stress biomarkers, beta-endorphin release, and the rate of cigarette smoking.</p> <p>Methods</p> <p>Volunteer smokers were randomly divided into four groups: group 1: VC supplement; group 2: exercise with VC supplement; group 3: exercise; and group 4: control. VC was prepared by wash and dry techniques and taken orally before smoking, matching the frequency of strenuous exercise (three times weekly). Before and after a two month period, exhaled carbon monoxide (CO), blood oxidative stress (malondialdehyde [MDA], nitric oxide [NOx], protein hydroperoxide [PrOOH] and total antioxidant capacity [TAC]), beta-endorphin and smoking rate were measured, and statistically analyzed.</p> <p>Results</p> <p>In Group 1, MDA, PrOOH, and NOx significantly decreased, whereas TAC increased (p < 0.05). In Group 2, MDA and PrOOH decreased (p < 0.05), with no other changes noted (p > 0.05). In Group 3, MDA, PrOOH, NOx, TAC, and beta-endorphin levels increased significantly (p < 0.05). Group 4 showed no change in oxidative stress variables or beta-endorphine levels (p > 0.05). All groups had lower levels of CO after the intervention. The smoking rate for light cigarette decreased in group 2(62.7%), 1(59.52%), 3 (53.57%) and 4(14.04%), whereas in self-rolled cigarettes it decreased in group 1 (54.47%), 3 (42.30%), 2 (40%) and 4 (9.2%).</p> <p>Conclusion</p> <p>Supplementation with <it>Vernonia cinerea </it>Less and exercise provided benefit related to reduced smoking rate, which may be related to oxidaive stress and beta-endorphine levels.</p

A Fragment of the LG3 Peptide of Endorepellin Is Present in the Urine of Physically Active Mining Workers: A Potential Marker of Physical Activity

Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24 h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic/anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3/endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk/survival

Studying lunar Irregular Mare Patches and lava tubes with the Lunar Geology Orbiter

INTRODUCTION A better understanding of lunar geology is critical both scientifically and practically for exploring and settling the Moon in the next decades. Improving our knowledge about the formation and evolution of the Moon helps us 1) to understand the geology of Earth and other terrestrial bodies in the Solar System, and 2) to prepare for in-situ utilisation of lunar resources. Irregular mare patches (IMPs), as well as lava tubes, pits and caves are such lunar geological phenomena that offer progress with both tasks. Even though multiple IMPs were found on the surface of the Moon, their age and formation processes remain enigmatic. Furthermore, many pits have been detected in various lunar geological settings, but it remains uncertain whether any of these openings could lead to extended cave conduits underground. The proposed Lunar Geology Orbiter LUGO aims primarily to reveal the formation ages and mechanisms of IMPs, and secondarily to identify the distribution and dimensions of lava tubes for future exploration. WHY IRREGULAR MARE PATCHES? Controversy surrounds the formation age of IMPs because very few impact craters are present at their surface. Whereas one scenario assumes that IMPs consist of compact igneous rocks and thus are relatively young (>100 My), another scenario assumes the existence of old (<3 Gy) but highly vesicular lava foams [1, 2]. The general shape of IMPs and their rugged landform characteristics are well known, but available Digital Terrain Models do not allow unambiguous determination of the properties of the material(s) in which the observed impact craters were formed. It is hence still impossible to distinguish between two possible scenarios for the formation of IMPs [1]. Recently, analysis of hyperspectral data revealed that darker deposits surrounding some IMPs as well as the IMP surfaces themselves contain little to no glassy material, and are barely distinguishable mineralogically from the surrounding mare material [3]. Despite these discoveries, it remains unclear how IMPs originated and what their actual age is, with far-reaching consequences for understanding the thermal evolution of small planetary bodies. For example, young age of IMPs might suggest that we could still expect volcanic eruptions on the Moon. WHY LUNAR LAVA TUBES? Lava tubes are underground voids that can be tens of kilometers long and tens of meters wide and are formed when the solidified roof of a lava flow remains after lava supply ends and the lava channel is drained out. Even if the detection of subsurface lava tunnels on the Moon is currently difficult [4], their existence is suggested by the presence of lunar pits, or skylights, which are collapsed features on the lunar surface with near-vertical walls. However, there is still no clear confirmation of continuations of lava tunnels from these potential entrances, and no map of their distribution exists yet. Detection of lava tubes by LUGO would enable us to evaluate their basic characteristics (size, length, depth) as well as the potential for subsurface habitat utilization in the future, where future crews would be shielded from micrometeorites and cosmic radiation [5]. The identification of lava tube dimensions and morphology together with surface observations and composition of the lava would enable estimating the effusion rate, viscosity and related temperature of lunar lava under lower specific gravity. LUGO payloads To achieve the objectives of LUGO, the orbiter would collect targeted imagery and topographic data of the lunar surface and subsurface at a very high resolution from a highly eccentric orbit by a quartet of payloads: a ground penetrating radar (GPR), a LiDAR, a hyperspectral camera, and a narrow-angle camera (NAC). Combining such measurements would allow to characterise: a) the regolith thickness over IMPs’ and surrounding units and hence reveal whether IMPs were formed recently or in the distant past, b) the properties of the material forming IMPs and hence to find out if they are formed by lava foams or lava flows, c) variations in their spectral compositions across the lunar surface, d) boulder density and distribution estimates as a proxy of regolith maturity, e) nature of the subsurface volcanic feeder system to IMPs. Furthermore, these payloads will allow to compare the subsurface detection of lava tubes as voids (with the GPR) with morphological indicators at the lunar surface (with the stereo-capability of the NAC). The proposed payloads could also allow unprecedented investigations of secondary geological targets such as floor-fractured craters and lunar domes. Future investigations could assess if an end-of-mission impact on an IMP target could provide critical information regarding the lithological properties of IMPs. The LUGO mission concept could provide a feasible way to explore these unknown aspects and could be adapted to fit funding and logistical restrictions. A LUGO mission would provide efficient synergies with already planned lunar missions, and will serve as a blueprint for future repeated observation missions that will help uncover the relation between the geological characteristics and structures at the lunar surface and the geological architecture of the shallow lunar crust