Investigating the Chemical Signatures of Cold-Climate Alteration on Mars at a Glaciated Volcanic Complex in the Oregon Cascades

No abstract availabl

Weathering in the Forelands of Two Rapidly Retreating Alpine Glaciers of Volcanic Bedrock in the Three Sisters, Oregon, USA

The glaciers of the Three Sisters volcanoes in Cascadia have retreated dramatically over the past century. In order to understand ongoing chemical weathering and solute transport in the proglacial valleys, waters were sampled from glacier outwash streams, local snowmelt, and proglacial springs and lakes at Collier and Diller Glaciers. To understand weathering and transport processes in the proglacial plains, infrared orbital remote sensing data was used to map compositional variability and highlight weathering products, which were then ground-truthed with laboratory mineralogical and chemical analyses of sediments. The hydrochemistry is significantly affected by a sub- and proglacial mafic weathering system lacking carbonate minerals. Here we report major ion concentrations in meltwaters for the summer 2016 and 2017 melt seasons. Total cation concentrations range from 3 to 250 eq/l and dissolved bicarbonate concentrations range from 2 to 200 eq/l. Other dissolved anions are negligible compared to bicarbonate. Dissolved silica concentrations range from 2 to 260 mol/l, comparable to total dissolved cation concentrations. The highest cation and silica concentrations were measured in moraine-sourced springs. Compositional remote sensing analysis identified alteration zones in the proglacial plains at both Collier and Diller indicating potential hydrated silica. This analysis is consistent with laboratory analysis of sediment samples, which indicate the presence of poorly crystalline phases weathering products, including hydrated silica. Weathered materials are preferentially deposited on moraines due to aeolian and glacial transport, as well as intra-moraine alteration, and at abandoned stream terraces due to fluvial transport. Geochemical measurements indicate that the predominant form of chemical weathering in these periglacial mafic systems is the carbonation of feldspar as well as reactive volcanic glass. The presence of poorly crystalline silicates, as indicated by remote sensing datasets and laboratory analysis, is consistent with rapid weathering of feldspars and glass and formation of Fe-Al-Si-bearing mineraloids in these proglacial valleys. This weathering regime has wide-ranging implications for atmospheric CO2 drawdown due to cold-climate volcanic rock weathering

Hindsight: review of preclinical disease models for the development of new treatments for uveal melanoma

The molecular, histopathological, genomic and transcriptomic characteristics of uveal melanoma (UM) have identified four molecular subgroups with different clinical outcomes. Despite the improvements in UM classification and biological pathology, current treatments do not reduce the occurrence of metastasis. The development of effective adjuvant and metastatic therapies for UM has been slow and extremely limited. Preclinical models that closely resemble the molecular and genetic UM subgroups are essential for translating molecular findings into improved clinical treatment. In this review, we provide a retrospective view of the existing preclinical models used to study UM, and give an overview of their strengths and limitations. We review targeted therapy clinical trial data to evaluate the gap in the translation of preclinical findings to human studies. Reflecting on the current high attrition rates of clinical trials for UM, preclinical models that effectively recapitulate the human in vivo situation and/or accurately reflect the subtype classifications would enhance the translational impact of experimental data and have crucial implications for the advancement of personalised medicine

1,4-dihydroxy quininib modulates the secretome of uveal melanoma tumour explants and a marker of oxidative phosphorylation in a metastatic xenograft model

Uveal melanoma (UM) is an intraocular cancer with propensity for liver metastases. The median overall survival (OS) for metastatic UM (MUM) is 1.07 years, with a reported range of 0.84-1.34. In primary UM, high cysteinyl leukotriene receptor 1 (CysLT(1)) expression associates with poor outcomes. CysLT(1) antagonists, quininib and 1,4-dihydroxy quininib, alter cancer hallmarks of primary and metastatic UM cell lines in vitro. Here, the clinical relevance of CysLT receptors and therapeutic potential of quininib analogs is elaborated in UM using preclinical in vivo orthotopic xenograft models and ex vivo patient samples. Immunohistochemical staining of an independent cohort (n = 64) of primary UM patients confirmed high CysLT(1) expression significantly associates with death from metastatic disease (p = 0.02; HR 2.28; 95% CI 1.08-4.78), solidifying the disease relevance of CysLT(1) in UM. In primary UM samples (n = 11) cultured as ex vivo explants, 1,4-dihydroxy quininib significantly alters the secretion of IL-13, IL-2, and TNF-alpha. In an orthotopic, cell line-derived xenograft model of MUM, 1,4-dihydroxy quininib administered intraperitoneally at 25 mg/kg significantly decreases ATP5B expression (p = 0.03), a marker of oxidative phosphorylation. In UM, high ATP5F1B is a poor prognostic indicator, whereas low ATP5F1B, in combination with disomy 3, correlates with an absence of metastatic disease in the TCGA-UM dataset. These preclinical data highlight the diagnostic potential of CysLT(1) and ATP5F1B in UM, and the therapeutic potential of 1,4-dihydroxy quininib with ATP5F1B as a companion diagnostic to treat MUM

Minimally invasive surgery and cancer: controversies part 1

Perhaps there is no more important issue in the care of surgical patients than the appropriate use of minimally invasive surgery (MIS) for patients with cancer. Important advances in surgical technique have an impact on early perioperative morbidity, length of hospital stay, pain management, and quality of life issues, as clearly proved with MIS. However, for oncology patients, historically, the most important clinical questions have been answered in the context of prospective randomized trials. Important considerations for MIS and cancer have been addressed, such as what are the important immunologic consequences of MIS versus open surgery and what is the role of laparoscopy in the staging of gastrointestinal cancers? This review article discusses many of the key controversies in the minimally invasive treatment of cancer using the pro–con debate format

A Rare Thyroid Metastasis from Uveal Melanoma and Response to Immunotherapy Agents

Thyroid metastasis is a rare occurrence with cutaneous melanoma and even more uncommon with uveal melanoma. The management of such metastasis is uncertain due to its infrequency and, in the era of immunotherapy, the effect of these novel drugs on uncommon metastasis, such as to the thyroid, is unknown. We report the rare case of a thyroid metastasis in a patient diagnosed with ocular melanoma initially managed with enucleation. Metastatic disease developed in the lung and thyroid gland. The case patient received the immunotherapy ipilimumab with stable disease in the thyroid and progressive disease elsewhere. The patient was then further treated with a second immunotherapy agent, pembrolizumab, and remains with stable disease one year later. We discuss the current literature on thyroid metastases from all causes and the optimal known management strategies. Furthermore, we provide an original report on the response of this disease to the novel immunomodulators, ipilimumab, and pembrolizumab with stable disease four years after initial diagnosis of ocular melanoma

Psychometric analysis of the International Olympic Committee’s Sport Mental Health Assessment Triage Tool among non-elite amateur adult athletes

Background: The International Olympic Committee developed the Sport Mental Health Assessment Tool-1, encompassing the Athlete Psychological Strain Questionnaire (APSQ) used for initial screening of mental ill-being symptoms and risk in elite athletes. Despite preliminary psychometric evidence, the APSQ has yet to be tested in non-elite amateur athletes, who represent the majority of sporting participants. The aim of the current study was to test the factor structure, cut-off point sensitivity, nomological validity, and test-retest reliability of the APSQ in non-elite amateur athletes.Method: Athletes (n = 605) aged 28.57 years (SD = 9.32) comprising 402 males (73.5%) completed the 10-item APSQ, alongside validated measures of anxiety, depression, and well-being. Two Confirmatory Factor Analysis models were tested, in addition to a series of receiver operating characteristics curves benchmarked against clinically relevant anxiety and depression symptoms to examine pre-defined and alternative cut-point sensitivity. Nomological validity was tested through Pearson’s correlations, and intraclass correlation coefficients were examined for test-retest reliability. Results: A higher-order APSQ model comprising a general ‘Psychological Strain’ factor, and three subcomponents of ‘External coping’, ‘Self-Regulation’ and ‘Performance’ was selected. Convergent and divergent validity were shown, and a new and revised, cut-point was found to have good classification accuracy within the study sample. Largely ‘fair-to-good’ test-retest reliability values were found. Conclusion: The APSQ could be considered for initial screening of athlete mental health symptoms by sports organisations, and may enable effective triaging to follow-up mental health assessment and/or supporting guidance, potentially preventing, or mitigating, short and long-term effects of mental ill-being. Further research should be undertaken to establish if the psychometric properties found amongst the present sample are generalisable to the broader amateur sporting population.<br/

Pharmacy Education and Training in Ireland. The PHARMINE survey of European higher education institutions delivering pharmacy education & training - Ireland, 2010.

Pharmacy education is provided for in Ireland by three Higher Education Institutions; The Royal College of Surgeons in Ireland (RCSI), University of Dublin, Trinity College (TCD), and University College Cork (UCC). TCD was the sole provider of the undergraduate programme from 1977 until 2002 when the School of Pharmacy RCSI opened. The Schools educate approximately 150 students per annum. Applications to study pharmacy are far in excess of the places available as demand is high, and the profession is therefore fortunate to attract students of high calibre. There have been a number of recent developments which have transformed the landscape of pharmacye ducation and training in Ireland. The Bologna declaration, for instance, prompted curriculum reform in the Schools with RCSI completely reforming in 2005 to be fully compliant. One of the main drivers for development has been the Pharmacy Act 2007, which conferred responsibility ont he Pharmaceutical Society of Ireland (PSI), the pharmacy regulator, for overseeing education, training and lifelong learning in pharmacy. The PSI recently commissioned The Review of Pharmacy Education and Accreditation (PEARs) Project, a Review of International CPD Models, a review of competency frameworks and a baseline survey of standards in practice. These are intended to inform undergraduate curriculum development and a strategy for lifelong learning. The primary recommendation of the PEARs report(http://www.pharmaceuticalsociety.ie/Education/upload/File/Accreditation/PEARs_Project_Report.pdf) is that “the current 4+1 model of pharmacy education to first registration should be replaced by a five year fully integrated programme of education, training and assessment as the basis for application for registration as a pharmacist.” This report will instigate major curriculum reform in the Higher Education Institutions imminently. The Review of International CPD Models(http://www.pharmaceuticalsociety.ie/News/upload/File/Publications/PSI_International_Review_of CPD_Models.pdf ) set forth a vision for continuing professional development provision that will be implemented by 2014, as mandated by the Pharmacy Act 2007. The PSI also prioritised reform of the pre‐registration year – the year of training between the undergraduatep rogramme and registration. The National Pharmacy Internship Programme, a globally unique programme, was developed on behalf of the PSI by the School of Pharmacy of the Royal College of Surgeons in Ireland. Successful completion of the programme results in the award of a Masters of Pharmacy (M.Pharm) and entitlement to apply for registration as a pharmacist in Ireland and for subsequent free movement within the EU/EEA under the Professional Qualification Directive (2005/36/EC). The programme is a 12 month, full‐time, blended‐learning programme, attracting 90 European Credit Transfer and Accumulation System (ECTS) credits on completion. The basis for the curriculum is a competency framework that describes the knowledge, skills and attitudes required of a newly registered pharmacist, consistent with international norms. It is envisaged that improvements in the education and training of pharmacists will allow for significante enhancements to be made to the delivery of pharmacy services that capable of being benchmarked against the best internationally.</p