De Soto’s First Headquarters in Florida

Knowing that Hernando de Soto, his expedition, and the places he visited will probably be matters of discussion for years and years, I have not recently ventured any further contributions regarding them. However, challenge of one of my conclusions, the probable site of the Indian town of Ucita where De Soto established his first North American headquarters, has recently been made in a scientifically motivated paper (“The Terra Ceia Site, Manatee County, Florida.” No. 3 of the Publications of the Florida Anthropological Society, by Ripley P. Bullen), and this calls for some comments

De Soto and Terra Cei

In connection with my work as chairman of the De Soto Expedition Commission between 1935 and 1938 I made a study of the documentary and geographical evidence regarding the location of the point where De Soto landed on the Florida coast in 1539 and the position of his first headquarters. While I was assisted to some extent by other members of the Commission, the conclusions reached were more particularly mine and I assume all responsibility for them. They were originally stated in a paper printed in “The Florida Historical Quarterly” (vol. XVI, no. 3; Jan. 1938) and were incorporated later in the “Final Report of the United States De Soto Expedition Commission” (Washington, 1939). The point where the greater part of the Spanish army was landed was believed to be Shaws Point, and the native town where he established his headquarters apparently at the Indian site on Terra Ceia Island

The Haida of Queen Charlotte Islands.

300 p. illus., XXVI pl., fold. maps, fold. geneal. tab. 36 cm

Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease

Lung cancer diagnostics have progressed greatly in the previous decade. Development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants, using smaller samples obtained via minimally invasive techniques, is a huge challenge. Tumour heterogeneity and cancer evolution in response to therapy means that repeat biopsies or circulating biomarkers are likely to be increasingly useful to adapt treatment as resistance develops. We highlight some of the current challenges faced in clinical practice for molecular testing of EGFR, ALK, and new biomarkers such as PDL1. Implementation of next generation sequencing platforms for molecular diagnostics in non-small-cell lung cancer is increasingly common, allowing testing of multiple genetic variants from a single sample. The use of next generation sequencing to recruit for molecularly stratified clinical trials is discussed in the context of the UK Stratified Medicine Programme and The UK National Lung Matrix Trial

Field relations, age, and tectonic setting of metamorphic and plutonic rocks in the Creignish Hills – North Mountain area, southwestern Cape Breton Island, Nova Scotia, Canada

 The Creignish Hills and North Mountain areas of southwestern Cape Breton Island consist mostly of Neoproterozoic rocks typical of the Ganderian Bras d’Or terrane. U-Pb ages presented here for detrital zircon in the Blues Brook Formation of the Creignish Hills confirm a depositional age no greater than about 600 Ma. Although it is possible that some components of the formation are much older, similarities in rock types and field relations suggest that this is not the case. It is likely that the equivalent Malagawatch Formation of the North Mountain area, as well as high-grade metasedimentary rocks of the Melford Formation and Chuggin Road complex in the Creignish Hills and Lime Hill gneiss complex in the North Mountain area, represent the same or stratigraphically equivalent units as the Blues Brook Formation. The minimum ages of all of these units are constrained by cross-cutting syn- and post-tectonic plutons with ages mostly between 565 and 550 Ma, indicating that sediments were deposited, regionally metamorphosed, deformed, and intruded by plutons in less than 40–50 million years. The assemblage of pelitic, psammitic, and carbonate rocks indicates that a passive margin in a tropical climate was quickly changed to an active Andean-type continental margin in which voluminous calcalkaline dioritic to granitic plutons were emplaced. This sedimentary and tectonic history is characteristic of the Bras d’Or terrane and is shared by its likely correlative, the Brookville terrane in southern New Brunswick.

Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and Multivessel Disease

BACKGROUND: The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction is uncertain.   OBJECTIVES: CvLPRIT (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized study comparing complete revascularization at index admission with treatment of the infarct-related artery (IRA) only.   METHODS: After they provided verbal assent and underwent coronary angiography, 296 patients in 7 U.K. centers were randomized through an interactive voice-response program to either in-hospital complete revascularization (n = 150) or IRA-only revascularization (n = 146). Complete revascularization was performed either at the time of P-PCI or before hospital discharge. Randomization was stratified by infarct location (anterior/nonanterior) and symptom onset (≤3 h or >3 h). The primary endpoint was a composite of all-cause death, recurrent myocardial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months.   RESULTS: Patient groups were well matched for baseline clinical characteristics. The primary endpoint occurred in 10.0% of the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after complete revascularization (p = 0.055 at 30 days). Although there was no significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen. There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced nephropathy, or stroke between the groups.   CONCLUSIONS: In patients presenting for P-PCI with multivessel disease, index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA. In such patients, inpatient total revascularization may be considered, but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival. (Complete Versus Lesion-only Primary PCI Pilot Study [CvLPRIT]; ISRCTN70913605)

Selective inhibition of the K⁺ efflux sensitive NLRP3 pathway by Cl^- channel modulation.

From Europe PMC via Jisc Publications RouterHistory: ppub 2020-10-01, epub 2020-10-12Publication status: PublishedFunder: Medical Research Council; Grant(s): MR/N029992/1, MC_PC_17172, MR/T016515/1Funder: Alzheimer's Society; Grant(s): AS-PhD-16-002, 10Funder: Alzheimers Research UK; Grant(s): ARUK-2015DDI-OXThe NLRP3 inflammasome regulates production of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, and contributes to inflammation exacerbating disease. Fenamate non-steroidal anti-inflammatory drugs (NSAIDs) were recently described as NLRP3 inflammasome inhibitors via chloride channel inhibition. Fenamate NSAIDs inhibit cyclooxygenase (COX) enzymes, limiting their potential as therapeutics for NLRP3-associated diseases due to established side effects. The aim here was to develop properties of the fenamates that inhibit NLRP3, and at the same time to reduce COX inhibition. We synthesised a library of analogues, with feedback from in silico COX docking potential, and IL-1β release inhibitory activity. Through iterative screening and rational chemical design, we established a collection of chloride channel inhibiting active lead molecules with potent activity at the canonical NLRP3 inflammasome and no activity at COX enzymes, but only in response to stimuli that activated NLRP3 by a K+ efflux-dependent mechanism. This study identifies a model for the isolation and removal of unwanted off-target effects, with the enhancement of desired activity, and establishes a new chemical motif for the further development of NLRP3 inflammasome inhibitors