An iridium anomaly at the Cretaceous/Tertiary boundary layer has been attributed to an extraterrestrial body that struck the Earth some 65 million years ago. It has been suggested that, during this event, the carrier of iridium was probably a micrometre-sized silicate-enclosed aggregate or the nanophase material of the vaporized impactor. But the fate of platinum-group elements (such as iridium) that regularly enter the atmosphere via ablating meteoroids remains largely unknown. Here we report a record of iridium and platinum fluxes on a climatic-cycle timescale, back to 128,000 years ago, from a Greenland ice core. We find that unexpectedly constant fallout of extraterrestrial matter to Greenland occurred during the Holocene, whereas a greatly enhanced input of terrestrial iridium and platinum masked the cosmic flux in the dust-laden atmosphere of the last glacial age. We suggest that nanometre-sized meteoric smoke particles, formed from the recondensation of ablated meteoroids in the atmosphere at altitudes >70 kilometres, are transported into the winter polar vortices by the mesospheric meridional circulation and are preferentially deposited in the polar ice caps. This implies an average global fallout of 14 +/- 5 kilotons per year of meteoric smoke during the Holocene.

Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most markers studied, median immune cell densities were at least two times higher in lymph node metastases compared to skin/subcutaneous ones; therefore, the prognostic and predictive associations of immune cell infiltration were evaluated separately in the two groups of metastases as well as in all samples as a whole. Higher prevalence of several immune cell types was seen in lymph node metastases of the responders compared to non-responders, particularly FOXP3 cells and CD8 T lymphocytes. In subcutaneous or cutaneous metastases, on the other hand, significant difference could be observed only in the case of CD16 and CD68. Associations of labeled cell densities with survival were also found for most cell types studied in nodal metastases, and for CD16 and CD68 cells in skin/s.c. metastatic cases. Our results corroborate the previous findings suggesting an association between an immunologically active tumor microenvironment and response to ipilimumab treatment, and propose new potential biomarkers for predicting treatment efficacy and disease outcome.

Our results pointed to utilisable NTG formulations and outcome measures for NTG-induced migraine models in mice. Pending further cross-validation with positive and negative control drugs in these mouse models and in the human NTG models of migraine, these tests might be valuable translational research tools for development of new anti-migraine drugs.

Background: Cardiac troponin I (cTnI) is used as a biomarker of myocardial injury in people and small animals. Little is known about the diagnostic use of cTnI in cattle.Hypothesis: Serum cTnI correlates to myocardial function and histopathologic lesions in cattle with monensin-induced myocardial injury.Animals: Ten healthy cows. Methods: Experimental study. Animals received 1 dose of monensin PO; 30 mg/kg (n 5 1) or 40 mg/kg (n 5 1) (Group A) or 50 mg/kg monensin (n 5 8) (Group B) of body weight. Repeated measurements were performed of serum cTnI, biochemistry, and ECG and echocardiography until study termination at 80 (Group A) and 144 hours (Group B) after dosing. Semiquantitative histopathologic examinations of the heart were performed in each cow. A scoring system with regard to the magnitude of myocardial injury was established and a total heart score was compared with maximum cTnI concentration measured after monensin administration. Five hearts from healthy cows served as controls.Results: Increased cTnI (40.07 ng/mL) was found in 9/10 cows. cTnI was significantly associated with left ventricular shortening fraction (r 2 5 0.51; P 5 .02) and myocardial histopathologic lesion score (r 2 5 0.49; P 5 .021). All cows (n 5 7) with evidence of myocardial necrosis had a cTnI concentration ! 1.04 ng/mL.Conclusion and Clinical Importance: cTnI is related to myocardial necrosis and severity of myocardial damage in cattle with monensin toxicosis. cTnI could become a useful diagnostic tool in the noninvasive assessment of myocardial injury in cattle with naturally occurring cardiac disease.

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