Miracle-dz/UniFAR-FTUs huggingface dataset:
Cycloserine and Linezolid for Tuberculosis Meningitis: Pharmacokinetic Evidence of Potential Usefulness.

BACKGROUND The ability of anti-tuberculosis drugs to cross the blood brain barrier and reach the central nervous system (CNS) is critical to their effectiveness in treating tuberculosis meningitis (TBM). We sought to fill a critical knowledge gap by providing data on the ability of new and repurposed anti-tuberculosis drugs to penetrate into the cerebrospinal fluid (CSF). METHODS We conducted a clinical pharmacology study among patients treated for TBM in Tbilisi,Georgia from January 2019 until January 2020. Serial serum and CSF samples were collected while patients were hospitalized. CSF was collected from routine lumbar punctures with the timing of the lumbar puncture alternating between 2 and 6 hours to capture early and late CSF penetration. RESULTS A total of seventeen patients treated for TBM (8 with confirmed diease) were included; all received linezolid, with a subset receiving cycloserine (5), clofazimine (5), delamanid (4) and bedaquiline (2). All CSF measurements of bedaquiline (12), clofazimine (24), and delaminid (19) were below the limit of detection. The median CSF concentrations of cycloserine at 2 and 6 hours were 15.90 and 15.10 µg/ml with adjusted CSF/serum ratios of 0.52 and 0.66. CSF concentrations of linezolid were 0.90 and 3.14 µg/ml at 2 and 6 hours, with adjusted CSF/serum ratios of 0.25 and 0.59, respectively. CSF serum linezolid concentrations were not impacted by rifampin coadministration. CONCLUSIONS Based on moderate to high CSF penetration, linezolid and cycloserine may be effective drugs for TBM treatment while the utility of bedaquiline, delaminid and clofazimine is uncertain given their low CSF penetration.
Geochemistry of Late Proterozoic Sendra Granitoid Suite, Central Rajasthan, India : Role of Magma Mixing/Hybridization Process in their Genesis

Cluster analysis based on major elements demonstrates existence of granite, granodiorite and tonalites as distinct natural sub-population in the Sendra granitoid suite. The peraluminous granite with limited variation in mineralogy and chemistry is characterised by higher total iron, K 2 O, mol. A/CNK, K 2 O/Na 2 O, Rb, Ba, Li and lower Sr as compared to the granodiorites and tonalites of the suite. Different trends for tonalites. granodiorites and granites in variation diagrams coupled with lower DI values of the granites in comparison to some of the tonalites and granodiorites, disallow interpretation of their relationship in terms of closed system equilibrium crystal fractionation or rcstite unmixing. Principal component analysis of the data negates the possibility of the geochemical variations being controlled by a single process. The presence of mafic microgranular enclaves (MME) in the granodiorite and tonalite suggest mixing of the felsic and mafic magmas. The homogeneous nature of the granite and the absence of tonalitic and granodioritic components in the Chang pluton are due to emplacement of unadulterated granitic melt generated in the lower crustal region by basaltic underplating. The granodiorite and tonalite with variable chemical composition, represent subsequent mixing of granitic melt with the underplating basaltic magma and different degrees of thermal and chemical disequilibrium in the hybrid magma.
The rising incidence of idiopathic pulmonary ﬁbrosis in the UK

Background Previous studies have shown that the incidence of idiopathic pulmonary ﬁbrosis (IPF) is rising in the UK and USA. Death registrations and primary care data were used to determine the current trends in IPF incidence in the UK. Because routine clinical data sets were used, the term IPF clinical syndrome (IPF-CS) is used to describe individuals in this study. Methods Age- and stratum-speciﬁc death registration rates between 1968 and 2008 were calculated and these were applied to the 2008 population to generate annual standardised expected number of deaths. Annual mortality rate ratios were calculated using Poisson regression. Computerised primary care records were used to determine incidence rates of IPF-CS between 2000 and 2008 stratiﬁed by age, sex and geographical region, and survival rates between calendar periods were compared. Results Annual death certiﬁcate recording of IPF-CS rose sixfold across the study period from 0.92 per 100 000 in the 1968 e 1972 calendar periods to 5.10 per 100 000 in the 2006 e 2008 calendar period, and were higher in men and the older age groups. The incidence of IPF-CS in primary care increased by 35% from 2000 to 2008, with an overall incidence rate of 7.44 per 100 000 person-years (95% CI 7.12 to 7.77). Incidence was higher in men, the older population and in Northwest England. Conclusions The incidence of IPF-CS in primary care and registered deaths from this cause in the UK continues to rise in the 21st century. The current ﬁndings suggest that there are > 5000 new cases diagnosed each year in the UK.
How hidden can malaria be in pregnant women? Diagnosis by microscopy, placental histology, polymerase chain reaction and detection of histidine-rich protein 2 in plasma.

BACKGROUND Accurate diagnosis of malaria infection during pregnancy remains challenging because of low parasite densities and placental sequestration of Plasmodium falciparum. The performance of different methods to detect P. falciparum in pregnancy and the clinical relevance of undetected infections were evaluated. METHODS P. falciparum infections were assessed in 272 Mozambican women at delivery by microscopy, placental histology, quantitative polymerase chain reaction (qPCR) and detection of histidine-rich protein 2 (HRP2) in plasma by enzyme-linked immunosorbent assay (ELISA) and a rapid diagnostic test (RDT). Association between infection and delivery outcomes was determined. RESULTS Among the 122 women qPCR-positive for P. falciparum in peripheral and/or placental blood samples, 87 (71.3%) did not receive a positive diagnosis by peripheral microscopy, 75 (61.5%) by HRP2 ELISA, and 74 (60.7%) by HRP2 RDT in plasma. Fifty-seven of the 98 qPCR-positive placental infections (58.2%) were not detected by histology. Women who were qPCR-positive but negative in their peripheral blood by microscopy or HRP2 RDT in plasma (n = 62) were at increased risk of anemia, compared with negative women (n = 141; odds ratio, 2.03; 95% confidence interval, 1.07-3.83; P = .029). CONCLUSIONS Microscopy, placental histology and HRP2-based plasma diagnostic methods fail to identify the majority of the P. falciparum infections detected by qPCR in peripheral and placental blood. Undetected infections were associated with maternal anemia, highlighting the urgent need for more accurate malaria diagnostic tools for pregnant women to avoid the negative clinical impact that hidden infections can have during pregnancy. CLINICAL TRIALS REGISTRATION NCT00209781.
Automatic detection of small moving targets in a five-ocular composite optical imaging system

It is quite difficult to realize the automatic detection and determination of the small moving targets by the images data captured from a mono-aperture imaging system. Therefore a five-ocular composite optical imaging system is designed. The system is constituted by an infrared imaging system in the center and four visible imaging subsystems around the center subsystem. According to the inner feature of the overlapping field of view in the five-ocular composite optical imaging system, the automatic detection and recognition algorithm of the small moving targets for this system is built up. The algorithm is divided into four steps: the first step is preprocessing to get rid of low frequency background pixels, the second step is detecting the candidates of the small moving targets in the high frequency images remained by preprocessing, the third step is determining the true small moving targets from the candidates, and the last step is combining the detecting results of the visible subsystems into the detecting results of the infrared subsystem to determine the small moving targets are "live" or "dead", because the "dead" targets with lower temperature are not observed in the infrared subsystem. The test result in the experimental system indicated that the designed detection and recognition algorithm increased the detecting probability of the small moving targets, and decreased the probability of false alarms. The detection and recognition method was proved to be feasible and effective.
In situ studies of the primary immune response to (4-hydroxy-3- nitrophenyl)acetyl. I. The architecture and dynamics of responding cell populations

After primary immunization with an immunogenic conjugate of (4-hydroxy- 3-nitrophenyl)acetyl, two anatomically and phenotypically distinct populations of antibody-forming cells arise in the spleen. As early as 2 d after immunization, foci of antigen-binding B cells are observed along the periphery of the periarteriolar lymphoid sheaths. These foci expand, occupying as much as 1% of the splenic volume by day 8 of the response. Later, foci grow smaller and are virtually absent from the spleen by day 14. A second responding population, germinal center B cells, appear on day 8-10 and persist at least until day 16 post- immunization. Individual foci and germinal centers represent discrete pauciclonal populations that apparently undergo somatic evolution in the course of the primary response. We suggest that foci may represent regions of predominantly interclonal competition for antigen among unmutated B cells, while germinal centers are sites of intraclonal clonal competition between mutated sister lymphocytes.
Fluorescent biological aerosol particle measurements at a tropicalhigh-altitude site in southern India during the southwestmonsoon season

Abstract. An ultraviolet aerodynamic particle sizer (UV-APS) was continuously operated for the first time during two seasons to sample the contrasting winds during monsoon and winter to characterize the properties of fluorescent biological aerosol particles (FBAPs), at a high-altitude site in India. Averaged over the entire monsoon campaign (1 June–21 August 2014), the arithmetic mean number and mass concentrations of coarse-mode (> 1 µm) FBAPs were 0.02 cm−3 and 0.24 µg m−3, respectively, which corresponded to ∼ 2 and 6 % of total aerosol loading, respectively. Average FBAP number size distribution exhibited a peak at ∼ 3 µm, which is attributed to the fungal spores, as supported by scanning electron microscope (SEM) images, and these results are consistent with previous studies made for FBAPs. During 11 weeks of measurements the variability of the total coarse-mode particle number (TAP) concentration was high compared to that observed in FBAP number concentrations. The TAP and FBAP number concentrations measured at this site were strongly dependent on changes in wind direction and rainfall. During periods of westerly/southwesterly winds with heavy persistent rainfall, the TAP and FBAP concentrations exhibited very low values (1.3 and 0.005 cm−3, respectively) with no significant diurnal variations, whereas during periods of northerly winds with scattered rainfall FBAPs exhibited relatively high concentration values (0.05 cm−3) with pronounced diurnal variations, which were strongly coupled with diurnal variations in meteorological parameters. The campaign-averaged FBAP number concentrations were shown to correlate with daily patterns of meteorological parameters and were positively correlated with relative humidity (RH; R2 = 0.58) and negatively with temperature (R2 = 0.60) and wind speed (R2 = 0.60). We did not observe any significant positive correlation with precipitation as reported by previous researchers from selected areas. These measurement results confirm the fact that the ratio of PBAPs to TAP is strongly dependent on particle size and location and thus may constitute a significant proportion of total aerosol particles.
Short-lived 1.9 Ga continental margin and its destruction, Wopmay orogen, northwest Canada

A 1.9 Ga continental margin in the northwest of the Canadian Shield evolved in less than 15 m.y. from a zone of crustal stretching, through a phase of passive-margin subsidence, to attempted subduction beneath an exotic(? ) microcontinent. Reversal of subduction polarity and generation of a major episutural magmatic arc occurred within 15 m.y. following microcontinental accretion. Terminal collision occurred 90 m.y. , at most, after initial rifting. Certain differences in detail between this collided margin and those of Phanerozoic age may be related to subduction of newly rifted lithosphere. Rapid evolution of the orogen, the contracted passive-margin phase in particular, is consistent with (but does not prove) more rapid recycling of oceanic plates at that time.
Use of a continuous probability scale to display visual field damage.

OBJECTIVE To derive and display the percentile score (1st-99th percentile) at each perimetric location of a standard automated perimetry test to determine whether this technique will uncover patterns of loss not visible in standard (StatPac) probability maps. METHODS We computed continuous scale probability plots of data collected from testing 305 visually healthy participants with standard automated perimetry (24-2 Swedish interactive thresholding algorithm). The age-corrected thresholds were sorted by sensitivity at each visual field location. Percentiles were derived in single increments from the 1st to the 99th. We displayed the percentiles as a color scale and then interpreted visual field plots from healthy control subjects and patients with visual system disorders. RESULTS Added information was achieved for identifying patterns of visual loss by using the 5th- to 20th-percentile range in conjunction with the lower range below the 5th percentile that is typically used. The extent of contiguous regional defects appeared larger using this method. Healthy control subjects often have threshold results within the 5th- to 20th-percentile range, but these test locations usually appeared randomly spaced rather than in contiguous patterns commonly seen in patients at the border of visual field defects. CONCLUSION Continuous scale probability plots are a potentially useful adjunct for interpretation of perimetry results.
A Heat-Balance Study on Mccall Glacier, Brooks Range, Alaska: A Contribution to the International Hydrological Decade

On the McCall Glacier, an Arctic glacier in the eastern Brooks Range, northern Alaska, a heat balance study was carried out during the summer of 1970 to investigate quantitatively the relationship between energy transfer, climatic parameters and melting processes. Considering the individual energy balance terms, it was found that radiation is the most important heat source for snow and ice melt. The melting period itself is only 11 weeks long, which is quite short. The evaporation overcompensates for what little condensation occurs, and amounts to about 2% of the total ablation. Evaporation is more important in the spring, but becomes decreasingly so during the summer. The melt water which percolates into the snow-pack and refreezes at a lower level is a more effective way of transporting energy into the ground than conduction, and is of importance during the beginning of the melt period. The summer balance is considerably less energetic than over the tundra north of the Brooks Range. The main difference is a higher surface albedo, and to a lesser extent the protected nature of the glacier in a deep valley on a N–S axis, which reduces the duration of possible sunshine by 39% in summer. These are the important factors in maintaining the McCall Glacier and other similar glaciers in an otherwise low precipitation area.
Upper Quaternary vegetation dynamics and palaeoclimatology of the La Chonta bog area (Cordillera de Talamanca, Costa Rica)

Two pollen records from La Chonta bog (2310 m altitude) and one pollen record of a soil profile (2430 m altitude) at a short distance from the bog permit the reconstruction of the vegetational history and climatic sequence of probably the last ca. 80 000 yr of the Cordillera de Talamanca, Costa Rica. The three pollen records can be correlated on the basis of three radiocarbon-dated horizons (> 39 900 yr BP, 34 850 yr BP and 1390 yr BP) and palynostratigraphy. Pollen concentration data provide indirect time control between radiocarbon-dated horizons of the La Chonta 2 core. During the Early Glacial successive fluctuations of the upper forest line occurred between ca. 2300 m and 2800 m altitude and the bog is alternately situated close to the subalpine rainforest belt and in the uppermontane rainforest belt. During the Pleniglacial (ca. 50 000-13 000 yr BP) the forest line fell to ca. 2000 m altitude and paramo vegetation surrounded the La Chonta site. During the Late Glacial the forest line shifted rapidly in ca. 270 yr to 2700–2800 m altitude and the lake became surrounded by Quercus-dominated upper montane rainforest during a period of ca. 1655 yr. A distinct climate cooling (by 2–2.5°C) followed during ca. 580 yr and the upper forest line dropped to ca. 2400 m altitude. This temperature rebound is probably equivalent to the Younger Dryas event. In the depression extensive Alnus carr and swamp vegetation developed. Finally, during the Holocene, the forest line shifted to 3300–3500 m elevation and the lower montane rainforest reached close to ca. 2300 m altitude. In the later part of the Holocene subparamo scrub with Hypericum, Puya, Compositae, Escallonia and Ericaceae largely replaced Alnus carr and the regional and local vegetation closely resembles the presentday composition. During the Last Glacial to Holocene transition a shift of the upper forest line of ca. 1400 m is inferred, corresponding to a glacial temperature depression at 2300 m altitude of ca. 8°C.
An air mass with high potential vorticity preceding the formation of the Marcus Convergence Zone

We examined the convective activity and dynamical field over the subtropical North Pacific by focusing on the relationship between upper cold lows (UCLs) and the formation of the Marcus Convergence Zone (MCZ). In mid‐July, we detected a UCL near Marcus Island that was associated with the formation of the MCZ. The convective activity associated with the MCZ followed the UCL, implying that the UCL contributed to the MCZ formation. Analysis of the temporal evolution of the dynamic field revealed that the UCL appeared in a large‐scale, high‐potential vorticity (PV) air mass migrating from the east. We had already identified the high‐PV region near the mid‐Pacific trough in late July. It stretched westward and reached Marcus Island in mid‐July, suggesting that the UCL in the high‐PV air mass over the North Pacific contributed to the formation of the MCZ.
True Triaxial Tests on Cross-Anisotropic Deposits of Fine Nevada Sand

AbstractAn experimental program was designed to study the effects of cross-anisotropy under three-dimensional conditions on fine Nevada sand using tall prismatic specimens. Eighteen drained tests were performed using a true triaxial apparatus. Specimens were created with both horizontal and vertical bedding planes by dry pluviation, then a freezing technique was used to solidify the specimens while they were mounted in the true triaxial apparatus. The specimens were then sheared at various b-values, where b=(σ2−σ3)/(σ1−σ3), in the three sectors of the octahedral plane. The stress-strain behavior and strength under various loading conditions on the octahedral plane are presented. Results show similar strength results in Sectors I and II. Effects of cross-anisotropy are shown when comparing the friction angles in Sectors I and II with those in Sector III. The strength is highest in Sector I, where the friction angle in triaxial compression (b=0.0, vertical specimen with horizontal bedding planes) is 5.3° hi.
Neurocomputational Underpinnings of Expected Surprise

Predictive coding accounts of brain functions profoundly influence current approaches to perceptual synthesis. However, a fundamental paradox has emerged, that may be very relevant for understanding hallucinations, psychosis, or cognitive inflexibility: in some situations, surprise or prediction error-related responses can decrease when predicted, and yet, they can increase when we know they are predictable. This paradox is resolved by recognizing that brain responses reflect precision-weighted prediction error. This presses us to disambiguate the contributions of precision and prediction error in electrophysiology. To meet this challenge for the first time, we appeal to a methodology that couples an original experimental paradigm with fine dynamic modeling. We examined brain responses in healthy human participants (N = 20; 10 female) to unexpected and expected surprising sounds, assuming that the latter yield a smaller prediction error but much more amplified by a larger precision weight. Importantly, addressing this modulation requires the modeling of trial-by-trial variations of brain responses, that we reconstructed within a fronto-temporal network by combining EEG and MEG. Our results reveal an adaptive learning of surprise with larger integration of past (relevant) information in the context of expected surprises. Within the auditory hierarchy, this adaptation was found tied down to specific connections and reveals in particular precision encoding through neuronal excitability. Strikingly, these fine processes are automated as sound sequences were unattended. These findings directly speak to applications in psychiatry, where specifically impaired precision weighting has been suggested to be at the heart of several conditions such as schizophrenia and autism. SIGNIFICANCE STATEMENT In perception as Bayesian inference and learning, context sensitivity expresses as the precision weighting of prediction errors. A subtle mechanism that is thought to lie at the heart of several psychiatric conditions. It is thus critical to identify its neurophysiological and computational underpinnings. We revisit the passive auditory oddball paradigm by manipulating sound predictability and use a twofold modeling approach to simultaneous EEG-MEG recordings: (1) trial-by-trial modeling of cortical responses reveals a context-sensitive perceptual learning process; (2) the dynamic causal modeling (DCM) of evoked responses uncovers the associated changes in synaptic efficacy. Predictability discloses a link between precision weighting and self-inhibition of superficial pyramidal (SP) cells, a result that paves the way to a fine description of healthy and pathologic perception.