Intra‐clinothem variability in sedimentary texture and process regime recorded down slope profiles

Shelf‐margin clinothem successions can archive process interactions at the shelf to slope transition, and their architecture provides constraints on the interplay of factors that control basin‐margin evolution. However, detailed textural analysis and facies distributions from shelf to slope transitions remain poorly documented. This study uses quantitative grain‐size and sorting data from coeval shelf and slope deposits of a single clinothem that crops out along a 5 km long, dip‐parallel transect of the Eocene Sobrarbe Deltaic Complex (Ainsa Basin, south‐central Pyrenees, Spain). Systematic sampling of sandstone beds tied to measured sections has captured vertical and basinward changes in sedimentary texture and facies distributions at an intra‐clinothem scale. Two types of hyperpycnal flow‐related slope deposits, both rich in mica and terrestrial organic matter, are differentiated according to grain size, sorting and bed geometry: (i) sustained hyperpycnal flow deposits, which are physically linked to coarse channelized sediments in the shelf setting and which deposit sand down the complete slope profile; (ii) episodic hyperpycnal flow deposits, which are disconnected from, and incise into, shelf sands and which are associated with sediment bypass of the proximal slope and coarse‐grained sand deposition on the medial and distal slope. Both types of hyperpycnites are interbedded with relatively homogenous, organic‐free and mica‐free, well‐sorted, very fine‐grained sandstones, which are interpreted to be remobilized from wave‐dominated shelf environments; these wave‐dominated deposits are found only on the proximal and medial slope. Coarse‐grained sediment bypass into the deeper‐water slope settings is therefore dominated by episodic hyperpycnal flows, whilst sustained hyperpycnal flows and turbidity currents remobilizing wave‐dominated shelf deposits are responsible for the full range of grain sizes in the proximal and medial slope, thus facilitating clinoform progradation. This novel dataset highlights previously undocumented intra‐clinothem variability related to updip changes in the shelf process‐regime, which is therefore a key factor controlling downdip architecture and resulting sedimentary texture

Diagnostic Criteria of Ulcerative Pyoderma Gangrenosum : A Delphi Consensus of International Experts

IMPORTANCE Pyoderma gangrenosum is a rare inflammatory skin condition that is difficult to diagnose. Currently, it is a "diagnosis of exclusion," a definition not compatible with clinical decision making or inclusion for clinical trials. OBJECTIVE To propose and validate diagnostic criteria for ulcerative pyoderma gangrenosum. EVIDENCE REVIEW Diagnostic criteria were created following a Delphi consensus exercise using the RAND/UCLA Appropriateness Method. The criteria were validated against peer-reviewed established cases of pyoderma gangrenosum and mimickers using k-fold cross-validation with methods of multiple imputation. FINDINGS Delphi exercise yielded 1 major criterion biopsy of ulcer edge demonstrating neutrophilic infiltrate and 8 minor criteria: (1) exclusion of infection; (2) pathergy; (3) history of inflammatory bowel disease or inflammatory arthritis; (4) history of papule, pustule, or vesicle ulcerating within 4 days of appearing; (5) peripheral erythema, undermining border, and tenderness at ulceration site; (6) multiple ulcerations, at least 1 on an anterior lower leg; (7) cribriform or "wrinkled paper" scar(s) at healed ulcer sites; and (8) decreased ulcer size within 1 month of initiating immunosuppressive medication(s). Receiver operating characteristic analysis revealed that 4 of 8 minor criteria maximized discrimination, yielding sensitivity and specificity of 86% and 90%, respectively. CONCLUSIONS AND RELEVANCE. This Delphi exercise produced 1 major criterion and 8 minor criteria for the diagnosis of ulcerative pyoderma gangrenosum. The criteria may serve as a guideline for clinicians, allowing for fewer misdiagnoses and improved patient selection for clinical trials

The exon 13 duplication in the BRCA1 gene is a founder mutation present in geographicaly diverse populations

Recently, a 6-kb duplication of exon 13, which creates a frameshift in the coding sequence of the BRCA1 gene, has been described in three unrelated U.S. families of European ancestry and in one Portuguese family. Here, our goal was to estimate the frequency and geographic diversity of carriers of this duplication. To do this, a collaborative screening study was set up that involved 39 institutions from 19 countries and included 3,580 unrelated individuals with a family history of the disease and 934 early-onset breast and/or ovarian cancer cases. A total of 11 additional families carrying this mutation were identified in Australia (1), Belgium (1), Canada (1), Great Britain (6), and the United States (2). Haplotyping showed that they are likely to derive from a common ancestor, possibly of northern British origin. Our results demonstrate that it is strongly advisable, for laboratories carrying out screening either in English-speaking countries or in countries with historical links with Britain, to include within their BRCA1 screening protocols the polymerase chain reaction-based assay described in this report