Long-term lead elimination from plasma and whole blood after poisoning

OBJECTIVE: Blood lead (B-Pb), one of the most used toxicological biomarker all kind, has serious limitations. Thus, the objective is to evaluate whether plasma lead (P-Pb) is more adequate. METHODS: A long-term follow-up study of five cases of lead poisoning. P-Pb was analysed by inductively coupled plasma mass spectrometry. Kinetics after end of exposure was modelled. RESULTS: P-Pb at severe poisoning was about 20 μg/L; haematological effects at about 5 μg/L. Biological half-time of P-Pb was about 1 month; B-Pb decay was much slower. CONCLUSION: P-Pb is a valuable biomarker of exposure to and risk, particularly at high exposure

Some exact results for the velocity of cracks propagating in non-linear elastic models

We analyze a piece-wise linear elastic model for the propagation of a crack in a stripe geometry under mode III conditions, in the absence of dissipation. The model is continuous in the propagation direction and discrete in the perpendicular direction. The velocity of the crack is a function of the value of the applied strain. We find analytically the value of the propagation velocity close to the Griffith threshold, and close to the strain of uniform breakdown. Contrary to the case of perfectly harmonic behavior up to the fracture point, in the piece-wise linear elastic model the crack velocity is lower than the sound velocity, reaching this limiting value at the strain of uniform breakdown. We complement the analytical results with numerical simulations and find excellent agreement.Comment: 9 pages, 13 figure

Supersonic crack propagation in a class of lattice models of Mode III brittle fracture

We study a lattice model for mode III crack propagation in brittle materials in a stripe geometry at constant applied stretching. Stiffening of the material at large deformation produces supersonic crack propagation. For large stretching the propagation is guided by well developed soliton waves. For low stretching, the crack-tip velocity has a universal dependence on stretching that can be obtained using a simple geometrical argument.Comment: 4 pages, 3 figure

Peroxidase-Generated Apoplastic ROS Impair Cuticle Integrity and Contribute to DAMP-Elicited Defenses

Cuticular defects trigger a battery of reactions including enhanced reactive oxygen species (ROS) production and resistance to necrotrophic pathogens. However, the source of ROS generated by such impaired cuticles has remained elusive. Here, we report the characterization of Arabidopsis thaliana ohyl mutant, a Peroxidase 57 (PER57) - overexpressing line that demonstrates enhanced defense responses that result both from increased accumulation of ROS and permeability of the leaf cuticle. The ohyl mutant was identified in a screen of A. thaliana seedlings for oligogalacturonides (OGs) insensitive/hypersensitive mutants that exhibit altered growth retardation in response to exogenous OGs. Mutants impaired in OG sensitivity were analyzed for disease resistance/susceptibility to the necrotrophic phytopathogens Botrytis cinerea and Pectobacterium carotovorum. In the ohyl line, the hypersensitivity to OGs was associated with resistance to the tested pathogens. This PER57 overexpressing line exhibited a significantly more permeable leaf cuticle than wild-type plants and this phenotype could be recapitulated by overexpressing other class III peroxidases. Such peroxidase overexpression was accompanied by the suppressed expression of cutin biosynthesis genes and the enhanced expression of genes associated with OG-signaling. Application of ABA completely removed ROS, restored the expression of genes associated with cuticle biosynthesis and led to decreased permeability of the leaf cuticle, and finally, abolished immunity to B. cinerea. Our work demonstrates that increased peroxidase activity increases permeability of the leaf cuticle. The loss of cuticle integrity primes plant defenses to necrotrophic pathogens via the activation of DAMP-responses.Peer reviewe

Prevention, Detection, and Management of Heart Failure in Patients Treated for Breast Cancer

Purpose of Review: Long-term survival has increased significantly in breast cancer patients, and cardiovascular side effects are surpassing cancer-related mortality. We summarize risk factors, prevention strategies, detection, and management of cardiotoxicity, with focus on left ventricular dysfunction and heart failure, during breast cancer treatment. Recent Findings: Baseline treatment of cardiovascular risk factors is recommended. Anthracycline and trastuzumab treatment constitute a substantial risk of developing cardiotoxicity. There is growing evidence that this can be treated with beta blockers and angiotensin antagonists. Early detection of cardiotoxicity with cardiac imaging and circulating cardiovascular biomarkers is currently evaluated in clinical trials. Chest wall irradiation accelerates atherosclerotic processes and induces fibrosis. Immune checkpoint inhibitors require consideration for surveillance due to a small risk of severe myocarditis. Cyclin-dependent kinases4/6 inhibitors, cyclophosphamide, taxanes, tyrosine kinase inhibitors, and endocrine therapy have a lower-risk profile for cardiotoxicity. Summary: Preventive and management strategies to counteract cancer treatment–related left ventricular dysfunction or heart failure in breast cancer patients should include a comprehensive cardiovascular risk assessment and individual clinical evaluation. This should include both patient and treatment-related factors. Further clinical trials especially on early detection, cardioprevention, and management are urgently needed. © 2020, The Author(s).Peer reviewe

Very static enforcement of dynamic policies

Security policies are naturally dynamic. Reflecting this, there has been a growing interest in studying information-flow properties which change during program execution, including concepts such as declassification, revocation, and role-change. A static verification of a dynamic information flow policy, from a semantic perspective, should only need to concern itself with two things: 1) the dependencies between data in a program, and 2) whether those dependencies are consistent with the intended flow policies as they change over time. In this paper we provide a formal ground for this intuition. We present a straightforward extension to the principal flow-sensitive type system introduced by Hunt and Sands (POPL’06, ESOP’11) to infer both end-to-end dependencies and dependencies at intermediate points in a program. This allows typings to be applied to verification of both static and dynamic policies. Our extension preserves the principal type system’s distinguishing feature, that type inference is independent of the policy to be enforced: a single, generic dependency analysis (typing) can be used to verify many different dynamic policies of a given program, thus achieving a clean separation between (1) and (2). We also make contributions to the foundations of dynamic information flow. Arguably, the most compelling semantic definitions for dynamic security conditions in the literature are phrased in the so-called knowledge-based style. We contribute a new definition of knowledge-based progress insensitive security for dynamic policies. We show that the new definition avoids anomalies of previous definitions and enjoys a simple and useful characterisation as a two-run style property

Phase-Field Model of Mode III Dynamic Fracture

We introduce a phenomenological continuum model for mode III dynamic fracture that is based on the phase-field methodology used extensively to model interfacial pattern formation. We couple a scalar field, which distinguishes between ``broken'' and ``unbroken'' states of the system, to the displacement field in a way that consistently includes both macroscopic elasticity and a simple rotationally invariant short scale description of breaking. We report two-dimensional simulations that yield steady-state crack motion in a strip geometry above the Griffith threshold.Comment: submitted to PR

Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density.

Background: Chronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury,yet the effects on normal cardiac mechanical performance are poorly understood. Methods: Pregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen)for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting. Results: CHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05).Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P <0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero. Conclusion: These data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance

Association between polymorphisms in RMI1, TOP3A, and BLM and risk of cancer, a case-control study

BACKGROUND: Mutations altering BLM function are associated with highly elevated cancer susceptibility (Bloom syndrome). Thus, genetic variants of BLM and proteins that form complexes with BLM, such as TOP3A and RMI1, might affect cancer risk as well. METHODS: In this study we have studied 26 tagged single nucleotide polymorphisms (tagSNPs) in RMI1, TOP3A, and BLM and their associations with cancer risk in acute myeloid leukemia/myelodysplatic syndromes (AML/MDS; N = 152), malignant melanoma (N = 170), and bladder cancer (N = 61). Two population-based control groups were used (N = 119 and N = 156). RESULTS: Based on consistency in effect estimates for the three cancer forms and similar allelic frequencies of the variant alleles in the control groups, two SNPs in TOP3A (rs1563634 and rs12945597) and two SNPs in BLM (rs401549 and rs2532105) were selected for analysis in breast cancer cases (N = 200) and a control group recruited from spouses of cancer patients (N = 131). The rs12945597 in TOP3A and rs2532105 in BLM showed increased risk for breast cancer. We then combined all cases (N = 584) and controls (N = 406) respectively and found significantly increased risk for variant carriers of rs1563634 A/G (AG carriers OR = 1.7 [95%CI 1.1-2.6], AA carriers OR = 1.8 [1.2-2.8]), rs12945597 G/A (GA carriers OR = 1.5 [1.1-1.9], AA carriers OR = 1.6 [1.0-2.5]), and rs2532105 C/T (CT+TT carriers OR = 1.8 [1.4-2.5]). Gene-gene interaction analysis suggested an additive effect of carrying more than one risk allele. For the variants of TOP3A, the risk increment was more pronounced for older carriers. CONCLUSION: These results further support a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk