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Source apportionment of fine particulate matter in middle Indo-Gangetic Plain by coupled radiocarbon –molecular organic tracer method
No full textDespite significant emissions of fine particulate matter (FPM) from the Indo-Gangetic Plain (IGP) that affect the climate and air quality in the region, the sources of these emissions are not adequately addressed. This research uses a combined radiocarbon-molecular organic tracer technique to investigate the degree of contamination, seasonal fluctuations, and contribution of FPM in the middle IGP (Patna), India. The findings indicated levoglucosan (L) as the single primary BB tracer chemical, ranging from 149 ng/m3 to 490 ng/m3 (median 282 ng/m3). Winter (median 462 ng/m3) showed a 2–3 times higher level of L than the monsoon season (median 180 ng/m3). A significant association of L with other organic tracers such as galactosan (G), mannosan (M), vallinic acid, syringic acid, p-hydroxybenzoic acid (pHA) and dehydroabietic acid (DHAA)(r = 0.53 to 0.89, p < 0.05), and moderate connection with Cl- (r = 0.21, p < 0.05), SO42- (r = 0.29, p < 0.05), and NO3- (r = 0.22, p < 0.05) indicated significant BB contribution. However, non-sea salt (nss-K+) was not related to L. Based on seven days of
air mass back trajectories and MODIS active fire counts analysis, we conclude that OAs composition is not the local origin but is also impacted by long-range atmospheric transport from Pakistan/Afghanistan, followed by the Bay of Bengal and the Arabian Sea. Chemical analysis of organic tracers and positive matrix factorization (PMF) modeling study identified three unique sources, i.e., biomass burning, secondary aerosols formation, and mixed type (fossil fuels and construction dust) as the primary source of FPM in Patna, accounted for 46.1 %, 28.9 %, and 24.9 %, of total emissions, respectively. The radiocarbon (14C) analysis of total carbon (TC) samples further supported this conclusion. The results of the 14C study indicated that emissions from BB, such as wood and stubble, were responsible for 57% of the TC concentration
Inclusive Hadronic Decay Rate of the τ Lepton from Lattice QCD: The u[over ¯]s Flavor Channel and the Cabibbo Angle.
Get PDFWe present a lattice determination of the inclusive decay rate of the process τ↦X_{us}ν_{τ} in which the τ lepton decays into a generic hadronic state X_{us} with u[over ¯]s flavor quantum numbers. Our results have been obtained in n_{f}=2+1+1 isosymmetric QCD with full nonperturbative accuracy, without any operator product expansion approximation and, except for the presently missing long-distance isospin-breaking corrections, include a solid estimate of all sources of theoretical uncertainties. This has been possible by using the Hansen-Lupo-Tantalo method [M. Hansen et al., Phys. Rev. D 99, 094508 (2019)PRVDAQ2470-001010.1103/PhysRevD.99.094508] that we have already successfully applied [A. Evangelista et al., Phys. Rev. D 108, 074513 (2023)PRVDAQ2470-001010.1103/PhysRevD.108.074513] to compute the inclusive decay rate of the process τ↦X_{ud}ν_{τ} in the u[over ¯]d flavor channel. By combining our first-principles theoretical results with the presently available experimental data, we extract the Cabibbo-Kobayashi-Maskawa matrix element |V_{us}|, the Cabibbo angle, with a 0.9% accuracy, dominated by the experimental error
Targeted Visual Prompting for Medical Visual Question Answering
No full textWith growing interest in recent years, medical visual question answering (Med-VQA) has rapidly evolved, with multimodal large language models (MLLMs) emerging as an alternative to classical model architectures. Specifically, their ability to add visual information to the input of pre-trained LLMs brings new capabilities for image interpretation. However, simple visual errors cast doubt on the actual visual understanding abilities of these models. To address this, region-based questions have been proposed as a means to assess and enhance actual visual understanding through compositional evaluation. To combine these two perspectives, this paper introduces targeted visual prompting to equip MLLMs with region-based questioning capabilities. By presenting the model with both the isolated region and the region in its context in a customized visual prompt, we show the effectiveness of our method across multiple datasets while comparing it to several baseline models
Scientific guidelines for preclinical research on potentised preparations manufactured according to current pharmacopoeias-the PrePoP guidelines.
Get PDFOBJECTIVE
Pharmacopoeias regulate the manufacture of potentised pharmaceutical preparations used in different branches of complementary and integrative medicine. The physicochemical properties and biological activity of these preparations are often investigated in preclinical research, yet no guidelines for experimental research currently exist in this area. The present PrePoP guidelines aim to provide recommendations to promote high-quality, statistically sound, and reproducible preclinical research on potentised preparations.
METHODS
Input was gathered from researchers nominated by the relevant scientific societies using a simplified Delphi consensus approach covering the most relevant aspects of basic research methodology in the field including appropriate controls, sample preparation and handling, and statistics. After three rounds of feedback, a consensus was finally reached on the most important aspects and considerations for conducting high-quality research on potentised preparations.
RESULTS
We present a series of recommendations on a range of topics including experimental controls, system stability, blinding and randomisation, environmental influences, and procedures for the preparation of potentised samples and controls, and we address some specific challenges of this research field.
CONCLUSION
This expert consensus process resulted in a robust set of methodological guidelines for research on potentised preparations and provides a valuable framework that will inform and improve the quality of subsequent research in this emerging field.
PLEASE CITE THIS ARTICLE AS
Tournier AL, Bonamin LV, Buchheim-Schmidt S, Cartwright S, Dombrowsky C, Doesburg P, Holandino C, Kokornaczyk MO, van de Kraats EB, López-Carvallo JA, Nandy P, Mazón-Suástegui JM, Mirzajani F, Poitevin B, Scherr C, Thieves K, Würtenberger S, Baumgartner S. Scientific guidelines for preclinical research on potentised preparations manufactured according to current pharmacopoeias-the PrePoP guidelines. J Integr Med. 2024; Epub ahead of print
Bayes on the court: Evidence for continuous prior-knowledge integration in virtual-reality tennis returns
Get PDFDue to noisy signals in the sensorimotor system, our perception is constantly subject to uncertainty. This is particularly evident in highly dynamic situations, such as returning a tennis serve. In fundamental research taking on a Bayesian approach to decision-making and sensorimotor control, it is argued that uncertainty is reduced by the reliability-weighted integration of current sensory information and accumulated prior knowledge (Körding & Wolpert, 2006). Therefore, we investigated this mechanism in a virtual-tennis return situation.
To this end, 32 young adults (22 females and 10 males, Mage = 21.0, SD = 2.5) learned two probability distributions of serve’s impact locations in a within-subject design over two days that differed regarding the central tendency closer to the left or the right of the service field. The kinematic information in the serving movement remained identical over all trials due to the identical avatar simulation. The perceptual demands in tracking the ball were high because of a speed similar to a serve in professional tennis. As an indicator of participants’ expectation of the ball-bounce location in action, we assessed the gaze fixation after the predictive saccade before the ball’s bounce.
A shift of the fixation in relation to the ball’s actual impact location towards the respective distribution’s central tendency was detected that, on top of this, increased over the acquisition period. These results perfectly fit a Bayesian explanatory framework since (1) Körding and Wolpert’s (2006) claim that prior knowledge is integrated into tennis returns according to Bayesian principles is empirically confirmed, and (2) prior-knowledge integration must be understood as a dynamic process in which the eye movements in the early phase of the return movement are increasingly affected by accumulated prior knowledge – which, to our knowledge, was empirically confirmed for complex sensorimotor behaviour for the first time by our study.
Körding, K. P. & Wolpert, D. M. (2006). Bayesian decision theory in sensorimotor control. Trends in Cognitive Sciences, 10(7), 319–326. doi: https://doi.org/10.1016/j.tics.2006.05.00
CT scan-based 3D fracture mapping in civilian gunshot intracapsular fractures of the femur neck.
Get PDFINTRODUCTION
Displaced intracapsular neck of femur (NOF) fractures secondary to civilian gunshots are rare injuries with universally poor outcomes following surgical fixation. No studies have been published on fracture mapping in NOF fractures secondary to civilian gunshots.
OBJECTIVES
We performed CT scan-based fracture mapping to identify the most common fracture patterns in these injuries.
METHODS
Design: Retrospective search of prospectively collected data.
SETTING
Single Level 1 Trauma hospital. Patient selection criteria: All patients presenting with gunshot fractures to the femur neck between 01 January 2009 and 31 December 2022 were identified. Once identified from Picture Archiving and Communication System (PACS), computed tomography (CT) scans in Digital Imaging and Communication in Medicine (DICOM) format were imported into Mimics 16 software and fracture fragments were segmented and three-dimensional (3D) reconstruction was generated. The reduced fractures were exported to 3-Matic software to merge the fragments and adjust the orientation in three planes. An uninjured femur model was used as a template for reduction. Fracture lines and heat maps were then generated. Our outcome measures were successful mapping of the identified fracture lines.
RESULTS
A total of 25 intracapsular femur neck fractures were identified and suitable for CT scan mapping. All patients were male with an average age of 22 (range 18-32). Once generated, fracture maps were used to show the location, distribution and frequency of the fracture lines. In all but two cases the fracture line propagation remained within the confines of the hip joint capsule. In three cases there was fracture extension into the superior aspect of the femur head, and in one case extension into the inferior aspect.
CONCLUSION
This is the first study to perform 3D fracture mapping for intracapsular femur neck fractures secondary to civilian gunshot injuries. The exercise has helped us better understand the commonest fracture patterns and assisted us with surgical planning and execution
Targeting valine catabolism to inhibit metabolic reprogramming in prostate cancer.
Get PDFMetabolic reprogramming and energetic rewiring are hallmarks of cancer that fuel disease progression and facilitate therapy evasion. The remodelling of oxidative phosphorylation and enhanced lipogenesis have previously been characterised as key metabolic features of prostate cancer (PCa). Recently, succinate-dependent mitochondrial reprogramming was identified in high-grade prostate tumours, as well as upregulation of the enzymes associated with branched-chain amino acid (BCAA) catabolism. In this study, we hypothesised that the degradation of the BCAAs, particularly valine, may play a critical role in anapleurotic refuelling of the mitochondrial succinate pool, as well as the maintenance of intracellular lipid metabolism. Through the suppression of BCAA availability, we report significantly reduced lipid content, strongly indicating that BCAAs are important lipogenic fuels in PCa. This work also uncovered a novel compensatory mechanism, whereby fatty acid uptake is increased in response to extracellular valine deprivation. Inhibition of valine degradation via suppression of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) resulted in a selective reduction of malignant prostate cell proliferation, decreased intracellular succinate and impaired cellular respiration. In combination with a comprehensive multi-omic investigation that incorporates next-generation sequencing, metabolomics, and high-content quantitative single-cell imaging, our work highlights a novel therapeutic target for selective inhibition of metabolic reprogramming in PCa
The 2023 - 2024 multi-source mpox outbreaks of Clade I MPXV in sub-Saharan Africa: alarm bell for Africa and the World.
Get PDFA population pharmacokinetic model for sertraline in women during the perinatal period-A contribution from the ConcePTION project.
Get PDFAIMS
Sertraline is frequently prescribed for mental health conditions in both pregnant and breastfeeding women. According to the limited available data, only small amounts of sertraline are transferred into human milk, yet with a large amount of unexplained interindividual variability. This study aimed to develop a population pharmacokinetic (popPK) model to describe the pharmacokinetics of sertraline during the perinatal period and explain interindividual variability.
METHODS
Pregnant women treated with sertraline were enrolled in the multicenter prospective cohort SSRI-Breast Milk study. A popPK model for sertraline maternal plasma and breast milk concentrations was developed and allowed estimating the milk-to-plasma ratio (MPR). An additional fetal compartment allowed cord blood concentrations to be described. Several covariates were tested for significance. Ultimately, model-based simulations allowed infant drug exposure through placenta and breast milk under various conditions to be predicted.
RESULTS
Thirty-eight women treated with sertraline were included in the study and provided 89 maternal plasma, 29 cord blood and 107 breast milk samples. Sertraline clearance was reduced by 42% in CYP2C19 poor metabolizers compared to other phenotypes. Doubling milk fat content increased the MPR by 95%. Simulations suggested a median daily infant dosage of 6.9 μg kg-1 after a 50 mg maternal daily dose, representing 0.95% of the weight-adjusted maternal dose. Median cord blood concentrations could range from 3.29 to 33.23 ng mL-1 after maternal daily doses between 25 and 150 mg.
CONCLUSIONS
Infant exposure to sertraline, influenced by CYP2C19 phenotype and breast milk fat content, remains low, providing reassurance regarding the use of sertraline during pregnancy and breastfeeding
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