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Abstract Continental deformation is known to be controlled by the interplay between tectonic and gravitational forces modulated by thermal relaxation-controlled lithospheric strength leading to oscillations around an equilibrium state, or to runaway extension. Using data-driven thermomechanical modelling of the Alpine Himalayan Collision Zone, we demonstrate how deviations from an equilibrium between mantle dynamics, plate-boundary forces, and the thermochemical configuration of the lithosphere control continental deformation. We quantify such balance between the internal energy of the plate and tectonic forces in terms of a critical crustal thickness, that match the global average of present-day continental crust. It follows that thicker intraplate domains than the critical crust (orogens) must undergo weakening due to their increased internal energy, and, in doing so, they dissipate the acquired energy within a diffused zone of deformation, unlike the localized deformation seen along plate boundaries. This evolution is controlled by a dissipative thermodynamic feedback loop between thermal and mechanical relaxation of the driving energy in the orogenic lithosphere. Exponentially growing energy states, leading to runaway extension are efficiently dampened by enhanced dissipation from radioactive heat sources. This ultimately drives orogens with their thickened radiogenic crust towards a final equilibrium state. Our results suggest a genetic link between the thermochemical state of the crust and the tectonic evolution of silicate Earth-like planets.

Abstract We analyzed the inclusion of sex and/or gender (S/G) in Head and Neck Cancer (HNC) clinical studies, through inspecting ClinicalTrials.gov (AACT) and the mention of Human Papilloma Virus (HPV) on a specific subgroup, namely oral cavity, larynx and oropharynx. Only 5% of HNC studies mention S/G as a planned analytical variable. Proportionally more observational studies treated S/G as an analytical variable than interventional studies (10% vs 5%, P-value ≤ 0.001), 8% of studies that mentioned S/G involved more than 100 subjects while 4% less than 100 (P-value ≤ 0.001). In randomized protocols, S/G was mentioned more in studies with a planned sample of more than 100 patients and including HPV status (P-value

Studies supporting a strong association between tau deposition and neuronal loss, neurodegeneration, and cognitive decline have heightened the allure of tau and tau-related mechanisms as therapeutic targets. In February 2020, leading tau experts from around the world convened for the first-ever Tau2020 Global Conference in Washington, DC, co-organized and cosponsored by the Rainwater Charitable Foundation, the Alzheimer's Association, and CurePSP. Representing academia, industry, government, and the philanthropic sector, presenters and attendees discussed recent advances and current directions in tau research. The meeting provided a unique opportunity to move tau research forward by fostering global partnerships among academia, industry, and other stakeholders and by providing support for new drug discovery programs, groundbreaking research, and emerging tau researchers. The meeting also provided an opportunity for experts to present critical research-advancing tools and insights that are now rapidly accelerating the pace of tau research.

Objective: In 2019 the American College of Obstetricians and Gynecologists (ACOG) issued specific recommendations for performance of antepartum fetal surveillance (AFS) based on individual risk factors. As similar recommendations were already in place at our institution, we have evaluated the impact of AFS on stillbirth (SB) occurrence in a 5-year cohort. Methods: Retrospective cohort study of all deliveries between 7/1/2013 and 6/30/2018. Excluded were multiples, anomalous fetuses or newborns, and deliveries before 32 0/7 weeks' gestation. AFS was conducted from 32 weeks with a modified biophysical profile, with a complete biophysical profile as back-up for non-reactive non-stress tests. All cases of SB were prospectively identified and individually reviewed to verify the presence of risk factors, the results of fetal testing if done, and calculate the interval between last fetal test and delivery. The electronic medical records during the study period were queried to identify women who underwent AFS and those who did not. Chi-square was used to compare the rates of SB between the two groups. Results: 16,827 women fulfilled the study inclusion and exclusion criteria, 5711 (34%) had risk factors which prompted AFS; 37% had 2 or more risk factors. SB occurred in 1.8‰ of them (10/5711) (3 had 1 risk factor, 5 had 2, and 2 had 3 risk factors). Rates of SB at ≥32.0 weeks were similar between women who had AFS and those who did not (1.8 vs. 2.3‰, p = 0.51, OR = 0.75, 95%CI 0.36–1.55). The false-negative rate at <7 days of a reassuring AFS among compliant women was 1.4‰ (8/5711). Rates of preterm delivery were similar in the tested vs untested population (6.5 vs. 6.0%, p = 0.22). Conclusion: Implementation of AFS in women with risk factors similar to those recommended by the ACOG may lower the risk of SB from 32 weeks to that of low-risk pregnancies. [ABSTRACT FROM AUTHOR]

The objective of this study is to demonstrate the potential of a multicompartmental mathematical model to simulate the activity of the gastrointestinal system after the intake of drugs, with a limited number of parameters. The gastrointestinal system is divided into five compartments, modeled as both continuous systems with discrete events (stomach and duodenum) and systems with delay (jejunum, ileum, and colon). The dissolution of the drug tablet occurs in the stomach and is described through the Noyes–Whitney equation, with pH dependence expressed through the Henderson–Hasselbach relationship. The boluses resulting from duodenal activity enter the jejunum, ileum, and colon compartments, where drug absorption takes place as blood flows countercurrent. The model includes only three parameters with assigned physiological meanings. It was tested and validated using data from in vivo experiments. Specifically, the model was tested with the concentration profiles of nine different drugs and validated using data from two drugs with varying initial concentrations. Overall, the outputs of the model are in good agreement with experimental data, particularly with regard to the time of peak concentration. The primary sources of discrepancy were identified in the concentration decay. The model’s main strength is its relatively low computational cost, making it a potentially excellent tool for in silico assessment and prediction of drug adsorption in the intestine.

The use of reclaimed wastewater for irrigation could result in the release of pharmaceutically active compounds (PhACs) and their metabolites into the agroecosystem. In this study, we investigated the fate of carbamazepine (CBZ) and its metabolites, with the aim of clarifying their behavior in a soil–plant system in a greenhouse experiment. The research was carried out using irrigation water especially fortified with high doses of CBZ (200 or 600 ppb) in order to evaluate the dynamics of CBZ and its metabolites in the soil and basil organs. The results of the study showed that CBZ is easily absorbed by the aerial part of the basil plant. The soil contained two metabolites of CBZ, namely acridine and carbamazepine-10,11-epoxide, as revealed by high-resolution mass spectrometry analyses. In addition, acridine was found in the aerial parts of basil plants. Furthermore, the greater presence of CBZ and its metabolites in bulk soil indicated a positive role of the basil rhizosphere in the degradation of such compounds or a positive role of the plant in the removal of the contaminant by uptake. Considering the observed morphological parameters and the mean CBZ content in wastewater, significantly lower than that used in the experiment, basil can be considered resistant to the application of irrigation water contaminated with CBZ.

To the Editor, Erectile dysfunction (ED) is one of the most prevalent conditions affecting men globally, with significant psychological and social consequences. The prevalence varies across different populations, and it is estimated around 50% in men aged between 40 to 70. The etiology of ED is multifactorial, involving a complex crosstalk between psychological, hormonal, neurogenic, vascular, and structural factors. Recently, the role of iron homeostasis (IH) is emerging. [...]

This study investigates the decades-long evolution of groundwater dynamics and thermal field in the North German Basin beneath Brandenburg (NE Germany) by coupling a distributed hydrologic model with a 3D groundwater model. We found that hydraulic gradients, acting as the main driver of the groundwater flow in the studied basin, are not exclusively influenced by present-day topographic gradients. Instead, structural dip and stratification of rock units and the presence of permeability contrasts and anisotropy are important co-players affecting the flow in deep seated saline aquifers at depths >500 m. In contrast, recharge variability and anthropogenic activities contribute to groundwater dynamics in the shallow (

Geothermal energy is one of the most viable sources of renewable heat. However, the potential risk of induced seismicity associated with geothermal operations may slow down the growth of the geothermal sector. Previous research has led to significant progress in understanding fluid-injection-induced seismicity in geothermal reservoirs. However, an in-depth assessment of thermal effects on the seismic risk was generally considered to be of secondary importance. This study aims to investigate the relative influence of temperature and key geological and operational parameters on the slip tendency of pre-existing faults. This is done through coupled thermo-hydro-mechanical simulations of the injection and production processes in synthetic geothermal reservoir models of the most utilized and potentially exploitable Dutch geothermal reservoir formations: Slochteren sandstone, Delft sandstone and Dinantian limestone.

Amphibians and reptiles are important ecological indicators of ecosystem status and play significant ecological roles. However, their populations are declining globally due to factors such as climate and land-use change. To effectively manage these species, it is crucial to study their distribution in protected areas. In this study, we provide new information on the distribution and ecology of amphibians and reptiles in the “Cilento, Vallo di Diano e Alburni” (CVDA) National Park in southern Italy. We used a comprehensive dataset consisting of 2465 records obtained from fieldwork, citizen science, and literature to evaluate species’ rarity, habitat preferences and community assemblage. We investigated whether differences in species richness across different habitat types and elevations resulted from species selection of different environmental conditions. We quantified species probability of observation in different habitat types and estimated the significance of species-habitat associations. Species rarity was assessed by considering geographic range, population abundance, and habitat breadth. Collected data substantially improved knowledge of the distribution of numerous species compared to published data. Our findings are generally consistent with the species’ ecological information available in Italy, but we also found some species’ peculiar ecological aspects that are little-known. The CVDA National Park emerges as an effective protected area that ensures good conservation status of the herpetofauna, also in the case of species showing population and range declines at the national scale.

Lysosomal storage diseases (LSDs) are inherited disorders caused by lysosomal deficiencies and characterized by dysfunction of the autophagy-lysosomal pathway (ALP) often associated with neurodegeneration. No cure is currently available to treat neuropathology in LSDs. By studying a mouse model of mucopolysaccharidosis (MPS) type IIIA, one of the most common and severe forms of LSDs, we found that multiple amyloid proteins including α-synuclein, prion protein (PrP), Tau, and amyloid β progressively aggregate in the brain. The amyloid deposits mostly build up in neuronal cell bodies concomitantly with neurodegeneration. Treating MPS-IIIA mice with CLR01, a "molecular tweezer" that acts as a broad-spectrum inhibitor of amyloid protein self-assembly reduced lysosomal enlargement and re-activates autophagy flux. Restoration of the ALP was associated with reduced neuroinflammation and amelioration of memory deficits. Together, these data provide evidence that brain deposition of amyloid proteins plays a gain of neurotoxic function in a severe LSD by affecting the ALP and identify CLR01 as new potent drug candidate for MPS-IIIA and likely for other LSDs.

The underpinnings of bipedal gait are reviewed from an evolutionary biology and prognostic health perspective to better understand issues and concerns related to cell phone use during ambulation and under conditions of distraction and interference. We also consider gait-related health issues associated with the fear of or risk of falling and include prognostic dimensions associated with cognitive decline, dementia, and mortality. Data were acquired on 21 healthy young adults without hearing loss, vestibular, balance, otological or neurological dysfunction using a computerized walkway (GAITRite® Walkway System) combined with specialized software algorithms to extract gait parameters. Four experimental conditions and seven temporo-spatial gait parameters were studied: gait velocity, cadence, stride length, ambulatory time, single-support time, double-support time, and step count. Significant main effects were observed for ambulation time, velocity, stride velocity, and double-support time. The greatest impact of distraction and interference occurred during the texting condition, although other significant effects occurred when participants were verbally responding to queries and passively listening to a story. These experimental observations show that relatively simple distraction and interference tasks implemented through the auditory sensory modality can induce significant perturbations in gait while individuals were ambulating and using a cell phone. Herein, emphasis is placed on the use of quantifiable gait parameters in medical, psychological, and audiological examinations to serve as a foundation for identifying and potentially averting gait-related disturbances.

One of the most frequent triggers of food anaphylaxis in pediatric age but also among the most common, early, and complex causes of childhood food allergy is cow’s milk protein allergy (CMPA). The diagnostic course and management of this allergy is defined in a complex clinical picture due to several factors. First of all, the epidemiological data are not uniform, mainly as a consequence of the diagnostic methodology used in the various studies and the different age ranges covered. In addition, there is the complexity of terminology, since although CMPA traditionally refers to immune-mediated reactions to cow’s milk, it is a term encompassing numerous clinical features with different symptoms and the requirement for specific treatments. Moreover, the differential diagnosis with other very frequent diseases, especially in the first year of life, such as gastro-esophageal reflux disease or colic, is still complex. This can result in misdiagnosis and incorrect treatment, with harmful health consequences and significant economic repercussions. In this context, the combination of several omics sciences together, which have already proved useful in clarifying the allergenicity of cow’s milk proteins with greater precision, could improve the diagnostic tests currently in use through the identification of new, more specific, and precise biomarkers that make it possible to improve diagnostic accuracy and predict the patient’s response to the various available treatments for the recovery of tolerance.