Purpose There are different mineral classes of asbestos, including serpentines and amphiboles. Chrysotile is the main type of serpentine and by far the most frequently used type of asbestos (about ...95% of world production and use). There has been continuing controversy over the capability of chrysotile asbestos to cause pleural and peritoneal mesothelioma. This review is to help clarify the issue by detailing cases and epidemiology studies worldwide where chrysotile is the exclusive or overwhelming fiber exposure. Methods A worldwide literature review was conducted of asbestos and associated mesothelioma including case series, case-control and cohort epidemiology studies searching for well documented chrysotile asbestos associated mesothelioma cases. Results Chrysotile asbestos exposures have occurred in many countries around the world from mining, manufacturing and community exposures. There have been many documented cases of mesothelioma from those exposures. Conclusions Chrysotile asbestos, along with all other types of asbestos, has caused mesothelioma and a world-wide ban of all asbestos is warranted to stop an epidemic of mesothelioma.
Pore fluids are ubiquitous throughout the lithosphere and are commonly invoked as the cause of induced seismicity and slow earthquakes. We perform lab experiments to address these questions for ...drained fault conditions and low pore pressure. We shear simulated faults at effective normal stress σn′ $\left({\sigma }_{n}^{\prime }\right)$ of 20 MPa and pore pressures Pp from 1 to 4 MPa. We document the full range of lab earthquake behaviors from slow slip to elasto‐dynamic rupture and show that slow slip can be explained by the slip rate dependence of the critical rheologic stiffness without dilatancy hardening or other fluid effects. Our fault permeabilities ranges from 10−18 to 10−17 m2 with an initial porosity of 0.1 and estimated fluid diffusion time ≈1 s. Slow slip and quasi‐dynamic fault motion may arise from high Pp at higher pressures but dilatancy strengthening is not a general requirement.
Plain Language Summary
Earthquakes begin and propagate within the fluid‐saturated rocks of Earth's crust. Many investigators have suggested that high pore fluid pressure (Pp) is essential for slow earthquakes and tremor. These studies rely on the idea that changes in Pp can impact rupture propagation speed by dilatant volume increase during faulting with concurrent increases in fault effective normal stress. Thus, understanding the processes that produce slow‐slip versus dynamically propagating rupture is integral to seismic hazard forecasting. Here, we describe experiments on granular faults that produce the full spectrum of slip observed in nature. We measure the mechanical and hydraulic behavior of the faults and determine that frictional and fluid‐driven processes occur in conjunction. Importantly, we demonstrate that frictional processes are sufficient to explain slow‐slip when fluid migration is not inhibited. We demonstrate that for low pore fluid pressures, the full transition from slow slip to dynamic rupture events can be explained as a frictional effect via the critical rheologic stiffness.
Key Points
The frictional stability transition does not require dilatant hardening for granular fault zones sheared at low pore pressures
Slow earthquakes and quasi‐dynamic fault slip can be explained by the strain‐rate dependence of the critical fault stiffness (Kc)
For the effective normal stresses studied, pore pressure has a negligible impact on frictional stability and the mode of fault slip
This study evaluated the potential role of immune cells and molecules in the pathogenesis and clinical course of pancreatic neuroendocrine tumors (PanNET).
Surgically resected PanNETs (
= 104) were ...immunohistochemically analyzed for Ki67 index, mitotic rate, macrophage, CD4
cells, and CD8
T-cell infiltration, as well as HLA class I, PD-L1, and B7-H3 expression. Results were correlated with clinicopathologic characteristics as well as with disease-free (DFS) and disease-specific (DSS) survival.
The median age of the 57 WHO grade 1 and 47 WHO grade 2 patients was 55 years. High intratumoral CD8
T-cell infiltration correlated with prolonged DFS (
= 0.05), especially when the number of tumor-associated macrophages (TAM) was low. In contrast, high peritumoral CD4
cell and TAM infiltration was associated with a worse DFS and DSS. PD-L1 and B7-H3 were expressed in 53% and 78% PanNETs, respectively. HLA class I expression was defective in about 70% PanNETs. HLA-A expression correlated with favorable DSS in PD-L1-negative tumors (
= 0.02). TAM infiltration (
= 0.02), WHO grade (
= 0.04), T stage (
= 0.01), and lymph node positivity (
= 0.04) were independent predictors of DFS. TAM infiltration (
= 0.026) and T stage (
= 0.012) continued to be predictors of DFS in WHO grade 1 PanNET patients. TAM infiltration was the sole independent predictor of DSS for WHO grade 1 and 2 patients (
= 0.02). Therefore, this biomarker may contribute to identifying WHO grade 1 patients with poor prognosis.
TAM infiltration appears to be the most informative prognostic biomarker in PanNET. It may represent a useful immunotherapeutic target in patients with PanNET.
We monitor dynamic rupture propagation during laboratory stick‐slip experiments performed on saw‐cut Westerly granite under upper crustal conditions (10–90 MPa). Spectral analysis of high‐frequency ...acoustic waveforms provided evidence that energy radiation is enhanced with stress conditions and rupture velocity. Using acoustic recordings band‐pass filtered to 400–800 kHz (7–14 mm wavelength) and high‐pass filtered above 800 kHz, we back projected high‐frequency energy generated during rupture propagation. Our results show that the high‐frequency radiation originates behind the rupture front during propagation and propagates at a speed close to that obtained by our rupture velocity inversion. From scaling arguments, we suggest that the origin of high‐frequency radiation lies in the fast dynamic stress‐drop in the breakdown zone together with off‐fault coseismic damage propagating behind the rupture tip. The application of the back‐projection method at the laboratory scale provides new ways to locally investigate physical mechanisms that control high‐frequency radiation.
Plain Language Summary
Over geological time scales, partially or fully locked tectonic plates accumulate stress and strain. The stress and the strain build up on discontinuities that we call “faults.” Natural faults exist either inside a tectonic plate or at the boundary between two distinct tectonic plates. When the stress accumulated on a fault exceeds the strength of the fault, the accumulated stress and strain, which can be interpreted in term of accumulated energy, are suddenly released. This natural phenomenon is called an “earthquake.” During an earthquake, part of the energy is released in the form of seismic waves. Those seismic waves are responsible for the ground shaking. High‐frequency waves usually cause most of the damage. To better understand the physical parameters that influence the generation of high‐frequency waves, we experimentally reproduced microearthquakes and used them as a proxy to study real earthquakes. Our results showed that the higher the pressure acting on the fault when an earthquake is generated, the higher the amount of high‐frequency radiations. Moreover, our observations underlined that, during an earthquake, high‐frequency waves are released in specific areas on the fault. Thus, these results might be of relevance to improve seismic hazard assessment.
Key Points
High‐frequency radiation is enhanced with both confining pressure and rupture velocity
Acoustic sensors can be used as an array to track high‐frequency sources during rupture propagation
High‐frequency radiation sources propagate consistently with the rupture front and are located behind it
This article investigates the appearance of instabilities in two planar coflowing fluid sheets with different densities and viscosities via experiments, numerical simulation and linear stability ...analysis. At low dynamic pressure ratios a convective instability is shown to appear for which the frequency of the waves in the primary atomization region is influenced by both liquid and gas velocities. For large dynamic pressure ratios an asymptotic regime is obtained in which frequency is solely controlled by gas velocity and the instability becomes absolute. The transition from convective to absolute is shown to be influenced by the velocity defect induced by the presence of the separator plate. We show that in this regime the splitter plate thickness can also affect the nature of the instability if it is larger than the gas vorticity thickness. Computational and experimental results are in agreement with the predictions of a spatio-temporal stability analysis.
Hypertension, coronary heart disease (CHD), and anxiety disorders all cause substantial morbidity to patients and costs to the healthcare system. Associations between these diseases have been ...hypothesized and studied for decades. In particular, psychosocial stressors associated with anxiety disorders raise autonomic arousal via the hypothalamic-pituitary axis which increases circulating catecholamines. This heightened arousal is associated with an increased risk of hypertension and a pro-inflammatory state and, consequently, development of coronary heart disease. This association holds across the spectrum of anxiety disorders (generalized anxiety, posttraumatic stress disorder, panic disorder, and obsessive compulsive disorder) and also when controlling for comorbid conditions such as depression and physical ailments. Multiple cross sectional studies reveal a positive association between anxiety and hypertension. These associations are bidirectional, with those with hypertension being more likely to have anxiety and those with anxiety being more likely to have hypertension. However, a few studies have shown no association. Longitudinal studies point to an increased risk of development of hypertension in patients who suffer from anxiety. More convincing studies show links between anxiety symptoms and disorders, including panic disorder and PTSD, and cardiovascular outcomes. Drawing broad conclusions from these studies is challenging, however, given the multiplicity of scales used to measure anxiety disorders. Anxiety, hypertension, and CHD are common conditions seen in primary care, and anxiety may be an important predictor of future CHD outcomes. Better recognition of the association of these conditions and the possible roles of each in development of the other should alert primary care providers to be vigilant in monitoring and treating anxiety, hypertension, and CHD.
Pre-exposure prophylaxis (PrEP) is a daily regimen that reduces the risk of acquiring HIV by up to 97%. There is limited information on the use of telehealth to provide PrEP in a program aimed toward ...the primary prevention of HIV. This was a 6-month telePrEP feasibility study that assessed process measures, clinical outcomes and patient satisfaction. Descriptive statistics and Chi-square analysis were used to evaluate measures and outcomes from the start to the end of the study. Twenty patients enrolled, and 80% completed the study. Participants were cisgender males (100%) with an average age of 35.6 years, white (95%), and were college graduates or higher (55%). The majority (75%) had very high comfort with video calls before the program. Self-reported adherence to PrEP medication remained high throughout the program (60%-70%). Without this program 31.2% of participants were unlikely to have received PrEP. For obtaining PrEP 56.3% preferred telemedicine only, and 31.2% preferred a combination of telemedicine and in-person office visits. PrEP is an effective method of preventing HIV infection for those at high risk. Our program shows that telemedicine can be useful to expand access to medication for patients at high risk.
During an earthquake, part of the released elastic strain energy is dissipated within the slip zone by frictional and fracturing processes, the rest being radiated away via elastic waves. While ...frictional heating plays a key role in the energy budget of earthquakes, it could not be resolved by seismological data up to now. Here we investigate the dynamics of laboratory earthquakes by measuring frictional heat dissipated during the propagation of shear instabilities at stress conditions typical of seismogenic depths. We estimate the complete energy budget of earthquake rupture and demonstrate that the radiation efficiency increases with thermal‐frictional weakening. Using carbon properties and Raman spectroscopy, we map spatial heat heterogeneities on the fault surface. We show that an increase in fault strength corresponds to a transition from a weak fault with multiple strong asperities and little overall radiation, to a highly radiative fault behaving as a single strong asperity.
Plain Language Summary
In nature, earthquakes occur when the stress accumulated in a medium is released by frictional sliding on faults. The stress released is dissipated into fracture and heat energy or radiated through seismic waves. The seismic efficiency of an earthquake is a measure of the fraction of the energy that is radiated away into the host medium. Because faults are at inaccessible depths, we reproduce earthquakes in the laboratory under natural in situ conditions to understand the physical processes leading to dynamic rupture. We estimate the first complete energy budget of an earthquake and show that increasing heat dissipation on the fault increases the radiation efficiency. We develop a novel method to illuminate areas of the fault that get excessively heated up. We finally introduce the concept of spontaneously developing heat asperities, playing a major role in the radiation of seismic waves during an earthquake.
Key Points
Spatial heat heterogeneities are imaged on a frictional interface using carbon properties and Raman spectroscopy
Rupture processes become more efficient with increasing slip on fault
Heating efficiency depends on time‐dependent memory effect of the fault surface
Changes in synaptic excitability and reduced brain metabolism are among the earliest detectable alterations associated with the development of Alzheimer's disease (AD). Stimulation of synaptic ...activity has been shown to be protective in models of AD beta-amyloidosis. Remarkably, deep brain stimulation (DBS) provides beneficial effects in AD patients, and represents an important therapeutic approach against AD and other forms of dementia. While several studies have explored the effect of synaptic activation on beta-amyloid, little is known about Tau protein. In this study, we investigated the effect of synaptic stimulation on Tau pathology and synapses in in vivo and in vitro models of AD and frontotemporal dementia (FTD). We found that chronic DBS or chemically induced synaptic stimulation reduced accumulation of pathological forms of Tau and protected synapses, while chronic inhibition of synaptic activity worsened Tau pathology and caused detrimental effects on pre- and post-synaptic markers, suggesting that synapses are affected. Interestingly, degradation via the proteasomal system was not involved in the reduction of pathological Tau during stimulation. In contrast, chronic synaptic activation promoted clearance of Tau oligomers by autophagosomes and lysosomes. Chronic inhibition of synaptic activity resulted in opposite outcomes, with build-up of Tau oligomers in enlarged auto-lysosomes. Our data indicate that synaptic activity counteracts the negative effects of Tau in AD and FTD by acting on autophagy, providing a rationale for therapeutic use of DBS and synaptic stimulation in tauopathies.
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