Reconstruction of the Free Energy in the Metastable Region using the Path Ensemble

By quenching into the metastable region of the three-dimensional Ising model, we investigate the paths that the magnetization (energy) takes as a function of time. We accumulate the magnetization (energy) paths into time-dependent distributions from which we reconstruct the free energy as a function of the magnetic field, temperature and system size. From the reconstructed free energy, we obtain the free energy barrier that is associated with the transition from a metastable state to the stable equilibrium state. Although mean-field theory predicts a sharp transition between the metastable and the unstable region where the free energy barrier is zero, the results for the nearest-neighbour Ising model show that the free energy barrier does not go zero

Dissecting a Zombie:Joint Analysis of Density and Resistivity Models Reveals Shallow Structure and Possible Sulfide Deposition at Uturuncu Volcano, Bolivia

The recent identification of unrest at multiple volcanoes that have not erupted in over 10 kyr presents an intriguing scientific problem. How can we distinguish between unrest signaling impending eruption after kyr of repose and non-magmatic unrest at a waning volcanic system? After ca. 250 kyr without a known eruption, in recent decades Uturuncu volcano in Bolivia has exhibited multiple signs of unrest, making the classification of this system as “active”, “dormant”, or “extinct” a complex question. Previous work identified anomalous low resistivity zones at <10 km depth with ambiguous interpretations. We investigate subsurface structure at Uturuncu with new gravity data and analysis, and compare these data with existing geophysical data sets. We collected new gravity data on the edifice in November 2018 with 1.5 km spacing, ±15 μGal precision, and ±5 cm positioning precision, improving the resolution of existing gravity data at Uturuncu. This high quality data set permitted both gradient analysis and full 3-D geophysical inversion, revealing a 5 km diameter, positive density anomaly beneath the summit of Uturuncu (1.5–3.5 km depth) and a 20 km diameter arc-shaped negative density anomaly around the volcano (0.5–7.5 depth). These structures often align with resistivity anomalies previously detected beneath Uturuncu, although the relationship is complex, with the two models highlighting different components of a common structure. Based on a joint analysis of the density and resistivity models, we interpret the positive density anomaly as a zone of sulfide deposition with connected brines, and the negative density arc as a surrounding zone of hydrothermal alteration. Based on this analysis we suggest that the unrest at Uturuncu is unlikely to be pre-eruptive. This study shows the value of joint analysis of multiple types of geophysical data in evaluating volcanic subsurface structure at a waning volcanic center

Sharp gene pool transition in a population affected by phenotype-based selective hunting

We use a microscopic model of population dynamics, a modified version of the well known Penna model, to study some aspects of microevolution. This research is motivated by recent reports on the effect of selective hunting on the gene pool of bighorn sheep living in the Ram Mountain region, in Canada. Our model finds a sharp transition in the structure of the gene pool as some threshold for the number of animals hunted is reached.Comment: 5 pages, 4 figure

Tuberculosis in children treated with second-line drugs under programmatic conditions in Lima, Peru.

OBJECTIVE: To characterise childhood tuberculosis (TB) treated with second-line drugs (SLDs) in Lima, Peru. DESIGN: Results for the age groups <5 and 5-14 years were compared and treatment outcomes were assessed in cases reported between 2011 and 2015 from six districts of Lima. RESULTS: Of 96 reported cases, 82 were evaluated. Among these, 59% were boys; the median age was 8 years and 32% were aged <5 years. Contact with a TB case was reported in 82% of cases; 90% were treatment-naïve, 98% had pulmonary localisation and 50% underwent the tuberculin skin test (purified protein derivative), with induration 10 mm in 88%. A positive smear was found in 40%, all in the 5-14 years age group, and 46% were culture-positive. Only 26% had confirmed multidrug-resistant TB, 90% of whom were in the 5-14 years age group. SLDs for confirmed or probable drug-resistant TB (DR-TB) were administered to all cases, with a high proportion of success (over 83%), no failures or deaths and a high proportion of loss to follow-up. CONCLUSION: The main indication for SLDs in childhood TB was the empirical treatment of DR-TB due to contact with one or more identified DR-TB patients. Bacteriological confirmation was limited; however, treatment success was adequate

Natural ventilation for the prevention of airborne contagion.

BACKGROUND: Institutional transmission of airborne infections such as tuberculosis (TB) is an important public health problem, especially in resource-limited settings where protective measures such as negative-pressure isolation rooms are difficult to implement. Natural ventilation may offer a low-cost alternative. Our objective was to investigate the rates, determinants, and effects of natural ventilation in health care settings. METHODS AND FINDINGS: The study was carried out in eight hospitals in Lima, Peru; five were hospitals of "old-fashioned" design built pre-1950, and three of "modern" design, built 1970-1990. In these hospitals 70 naturally ventilated clinical rooms where infectious patients are likely to be encountered were studied. These included respiratory isolation rooms, TB wards, respiratory wards, general medical wards, outpatient consulting rooms, waiting rooms, and emergency departments. These rooms were compared with 12 mechanically ventilated negative-pressure respiratory isolation rooms built post-2000. Ventilation was measured using a carbon dioxide tracer gas technique in 368 experiments. Architectural and environmental variables were measured. For each experiment, infection risk was estimated for TB exposure using the Wells-Riley model of airborne infection. We found that opening windows and doors provided median ventilation of 28 air changes/hour (ACH), more than double that of mechanically ventilated negative-pressure rooms ventilated at the 12 ACH recommended for high-risk areas, and 18 times that with windows and doors closed (p < 0.001). Facilities built more than 50 years ago, characterised by large windows and high ceilings, had greater ventilation than modern naturally ventilated rooms (40 versus 17 ACH; p < 0.001). Even within the lowest quartile of wind speeds, natural ventilation exceeded mechanical (p < 0.001). The Wells-Riley airborne infection model predicted that in mechanically ventilated rooms 39% of susceptible individuals would become infected following 24 h of exposure to untreated TB patients of infectiousness characterised in a well-documented outbreak. This infection rate compared with 33% in modern and 11% in pre-1950 naturally ventilated facilities with windows and doors open. CONCLUSIONS: Opening windows and doors maximises natural ventilation so that the risk of airborne contagion is much lower than with costly, maintenance-requiring mechanical ventilation systems. Old-fashioned clinical areas with high ceilings and large windows provide greatest protection. Natural ventilation costs little and is maintenance free, and is particularly suited to limited-resource settings and tropical climates, where the burden of TB and institutional TB transmission is highest. In settings where respiratory isolation is difficult and climate permits, windows and doors should be opened to reduce the risk of airborne contagion

Microscopic Observation Drug Susceptibility Assay for Rapid Diagnosis of Lymph Node Tuberculosis and Detection of Drug Resistance.

In this study, 132 patients with lymphadenopathy were investigated. Fifty-two (39.4%) were diagnosed with tuberculosis (TB). The microscopic observation drug susceptibility (MODS) assay provided rapid (13 days), accurate diagnosis (sensitivity, 65.4%) and reliable drug susceptibility testing (DST). Despite its lower sensitivity than that of other methods, its faster results and simultaneous DST are advantageous in resource-poor settings, supporting the incorporation of MODS into diagnostic algorithms for extrapulmonary TB

Effect of universal MODS access on pulmonary tuberculosis treatment outcomes in new patients in Peru.

SETTING: Primary health care centres in Callao, Peru. OBJECTIVES: To evaluate the effect of universal access to the microscopic-observation drug susceptibility (MODS) assay on treatment outcomes in new and primary multidrug-resistant tuberculosis (MDR-TB) patients and on the process of drug susceptibility testing (DST). DESIGN: Retrospective review of tuberculosis (TB) registers and clinical records before (2007) and after (2009) the introduction of MODS in 2008. RESULTS: There were 281 patients in each cohort. Favourable treatment outcomes for 2007 (81%) and 2009 (77%) cohorts were similar. There was an increase in loss to follow-up (from 6% to 10%, P = 0.04) and a reduction in failure rates (from 4% to 0.4%, P = 0.01) in the 2009 compared with the 2007 cohort. In new MDR-TB cases (n = 22), a favourable treatment outcome was improved (from 46% to 82%, P = 0.183) in the 2009 cohort. DST coverage improved (from 24% to 74%, P < 0.001), and a significant reduction in time to diagnosis of drug-susceptible (from 118 to 33 days, P < 0.001) and MDR-TB (from 158 to 52 days, P =30.003) was observed in the 2009 cohort. CONCLUSION: Universal access to MODS increased DST coverage, reduced the time required to obtain DST results and was associated with reduced failure rates. MODS can make an important contribution to TB management and control in Peru

Language in tuberculosis services: can we change to patient-centred terminology and stop the paradigm of blaming the patients?

The words 'defaulter', 'suspect' and 'control' have been part of the language of tuberculosis (TB) services for many decades, and they continue to be used in international guidelines and in published literature. From a patient perspective, it is our opinion that these terms are at best inappropriate, coercive and disempowering, and at worst they could be perceived as judgmental and criminalising, tending to place the blame of the disease or responsibility for adverse treatment outcomes on one side-that of the patients. In this article, which brings together a wide range of authors and institutions from Africa, Asia, Latin America, Europe and the Pacific, we discuss the use of the words 'defaulter', 'suspect' and 'control' and argue why it is detrimental to continue using them in the context of TB. We propose that 'defaulter' be replaced with 'person lost to follow-up'; that 'TB suspect' be replaced by 'person with presumptive TB' or 'person to be evaluated for TB'; and that the term 'control' be replaced with 'prevention and care' or simply deleted. These terms are non-judgmental and patient-centred. We appeal to the global Stop TB Partnership to lead discussions on this issue and to make concrete steps towards changing the current paradigm

Search for Intermediate Mass Magnetic Monopoles and Nuclearites with the SLIM experiment

SLIM is a large area experiment (440 m2) installed at the Chacaltaya cosmic ray laboratory since 2001, and about 100 m2 at Koksil, Himalaya, since 2003. It is devoted to the search for intermediate mass magnetic monopoles (107-1013 GeV/c2) and nuclearites in the cosmic radiation using stacks of CR39 and Makrofol nuclear track detectors. In four years of operation it will reach a sensitivity to a flux of about 10-15 cm-2 s-1 sr-1. We present the results of the calibration of CR39 and Makrofol and the analysis of a first sample of the exposed detector.Comment: Presented at the 22nd ICNTS, Barcelona 200

Protocol for studying cough frequency in people with pulmonary tuberculosis.

INTRODUCTION: Cough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution. METHODS: This study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociación Benéfica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed