Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies

Essentials An international collaboration provides a consensus for clinical definitions. This concerns thrombotic microangiopathies and thrombotic thrombocytopenic purpura (TTP). The consensus defines diagnosis, disease monitoring and response to treatment. Requirements for ADAMTS-13 are given. Summary: Background Thrombotic thrombocytopenic purpura (TTP) and hemolytic\ue2\u80\u93uremic syndrome (HUS) are two important acute conditions to diagnose. Thrombotic microangiopathy (TMA) is a broad pathophysiologic process that leads to microangiopathic hemolytic anemia and thrombocytopenia, and involves capillary and small-vessel platelet aggregates. The most common cause is disseminated intravascular coagulation, which may be differentiated by abnormal coagulation. Clinically, a number of conditions present with microangiopathic hemolytic anemia and thrombocytopenia, including cancer, infection, transplantation, drug use, autoimmune disease, and pre-eclampsia and hemolysis, elevated liver enzymes and low platelet count syndrome in pregnancy. Despite overlapping clinical presentations, TTP and HUS have distinct pathophysiologies and treatment pathways. Objectives To present a consensus document from an International Working Group on TTP and associated thrombotic microangiopathies (TMAs). Methods The International Working Group has proposed definitions and terminology based on published information and consensus-based recommendations. Conclusion The consensus aims to aid clinical decisions, but also future studies and trials, utilizing standardized definitions. It presents a classification of the causes of TMA, and criteria for clinical response, remission and relapse of congenital and immune-mediated TTP

Molecular targets for rapid identification of Brucella spp

BACKGROUND: Brucella is an intracellular pathogen capable of infecting animals and humans. There are six recognized species of Brucella that differ in their host preference. The genomes of the three Brucella species have been recently sequenced. Comparison of the three revealed over 98% sequence similarity at the protein level and enabled computational identification of common and differentiating genes. We validated these computational predictions and examined the expression patterns of the putative unique and differentiating genes, using genomic and reverse transcription PCR. We then screened a set of differentiating genes against classical Brucella biovars and showed the applicability of these regions in the design of diagnostic tests. RESULTS: We have identified and tested set of molecular targets that are associated in unique patterns with each of the sequenced Brucella spp. A comprehensive comparison was made among the published genome sequences of B. abortus, B. melitensis and B. suis. The comparison confirmed published differences between the three Brucella genomes, and identified subsets of features that were predicted to be of interest in a functional comparison of B. melitensis and B. suis to B. abortus. Differentiating sequence regions from B. abortus, B. melitensis and B. suis were used to develop PCR primers to test for the existence and in vitro transcription of these genes in these species. Only B. suis is found to have a significant number of unique genes, but combinations of genes and regions that exist in only two out of three genomes and are therefore useful for diagnostics were identified and confirmed. CONCLUSION: Although not all of the differentiating genes identified were transcribed under steady state conditions, a group of genes sufficient to discriminate unambiguously between B. suis, B. melitensis, and B. abortus was identified. We present an overview of these genomic differences and the use of these features to discriminate among a number of Brucella biovars

Late Precontact Settlement on the Northern Seward Peninsula Coast: Results of Recent Fieldwork

Changing Arctic settlement patterns are associated with shifts in socioeconomic organization and interaction at both the inter- and intraregional levels; analysis of Arctic settlement patterns can inform research on the emergence and spread of Arctic maritime adaptations. Changes in late precontact settlement patterns in Northwest Alaska suggest significant shifts in subsistence and/or social organization, but the patterns themselves are not well understood. Prior research around Kotzebue Sound suggests three possible scenarios: (1) population decrease and dispersion from settlement centers after 550 cal bp, (2) population stability and dispersion after 550 cal bp, and (3) different settlement patterns in the northern and southern areas of Kotzebue Sound. We analyze site distribution and radiocarbon data from new research on the northern Seward Peninsula coast to address questions about local late precontact settlement patterns. Our results point to denser late precontact occupation of this region than previously understood, suggesting either population stability and dispersion after 550 cal bp or the development of differential settlement patterns around the Kotzebue Sound region. This research provides new information about late precontact settlement patterns in Northwest Alaska and contributes to the broader debate about the changing nature of Arctic maritime adaptations during the dynamic late Holocene period. Results also indicate that people in this region were well integrated into both Kotzebue Sound and more distant socioeconomic systems despite potential reduction or change in interaction spheres during the late precontact period

Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies.

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are two important acute conditions to diagnose. Thrombotic Microangiopathy is a broad pathophysiological process that leads to microangiopathic hemolytic anemia, thrombocytopenia and involves capillary and small vessel platelet aggregates. The most common cause being disseminated intravascular coagulation (DIC), which may be differentiated by abnormal coagulation. Clinically, a number of conditions present with microangiopathic hemolytic anemia and thrombocytopenia (MAHAT), including cancer, infection, transplantation, drugs, autoimmune disease and pre-eclampsia and HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome in pregnancy. Despite overlapping clinical presentations, TTP and HUS have distinct pathophysiology and treatment pathways. OBJECTIVES Presented is a consensus document from an international working group on TTP and associated TMAs (thrombotic microangiopathies). METHODS The international working group has proposed definitions and terminology based on published information and consensus based recommendations. CONCLUSION The consensus aims to aid clinical decisions but also future studies and trials, utilizing standardized definitions. It presents classification of the causes of TMA, and criteria for clinical response, remission and relapse of congenital and immune mediated TTP. This article is protected by copyright. All rights reserved

Cultural Resources Survey of the Lone Star Express II Pipeline Project - Loop 2, in Nolan, Taylor, Callahan, and Eastland Counties, Texas

Gray & Pape, Inc., of Houston, Texas, on behalf of Lonestar NGL Pipeline, LP, conducted an intensive pedestrian cultural resources survey within permitted areas of the 117.85-kilometer (73.23-mile) long Lone Star Express II Pipeline Project – Loop 2, in Nolan, Taylor, Callahan, and Eastland Counties, Texas. The lead agency for the project has been identified as the United States Army Corps of Engineers, Fort Worth District (Permit No. SWF-2019-00234). Thus, survey efforts concentrated on areas anticipated to be under the jurisdiction of the United States Army Corps of Engineers (permit areas). Within Loop 2, the total Area of Potential Effects within the permit areas measures approximately 125.9 hectares (311 acres). This area encapsulates approximately 29 kilometers (18 miles) of the proposed project alignment. The procedures to be followed by the United States Army Corps of Engineers to fulfill the requirements set forth in the National Historic Preservation Act, other applicable historic preservation laws, and Presidential directives as they relate to the regulatory program of the United States Army Corps of Engineers (33 CFR Parts 320-334) are articulated in the Regulatory Program of the United States Army Corps of Engineers, Part 325 - Processing of Department of the Army Permits, Appendix C - Procedures for the Protection of Historic Properties. All fieldwork and reporting activities were completed according to a scope of work submitted to the United States Army Corps of Engineers and the Texas Historical Commission and accepted standards set forth by the Texas Historical Commission and the Council of Texas Archeologists and in accordance with Section 106 of the National Historic Preservation Act. A records and literature review of the project location prior to the survey identified 17 previously recorded archaeological resources, one cemetery, one historic marker, and 17 previously conducted surveys within a 0.8-kilometer (0.5-mile) radius of the Loop 2 segment. Of those, six recorded archaeological resources are within 91 meters (300 feet) of the project corridor and four previous surveys intersect the project alignment. Fieldwork on Loop 2 was initially conducted in Spring 2019, with supplemental investigations taking place in August, October, and November of 2019. Survey of Loop 2 required approximately 2,320 person-hours to complete and involved archaeological reconnaissance and shovel testing throughout anticipated permit areas within the project corridor. In total, approximately 677 shovel tests were excavated within permit areas and beyond in cases of site delineation, of which six within the APE were positive for cultural materials. A total of 14 mechanical auger tests were conducted within Permit Area 6 at Mulberry Creek. All were negative for cultural materials. Five previously recorded resources: 41NL318, 41TA353, 41TA354, 41TA314, and 41CA27; six new resources: 41TA396, 41TA397, 41TA398, 41TA399, 41CA42, and 41CA43; and two isolate finds were identified within Loop 2 permit areas. Materials were identified adjacent to one additional previously identified resource, 41TA371, located outside of Project Permit Areas. The material consisted of only two artifacts found on the surface in a disturbed context. Thus, the site was not expanded into the current Area of Potential Effects. Four resources are of a historic age or have a historic component: 41NL318, 41TA396, 41TA397, and 41TA399. Historic components generally consist of early to mid-twentieth century and twentieth-century materials representative of trash dumps. Site 41NL318 contains a remnant of a private drive/road and associated wooden bridge. The remainder of the resources are prehistoric. Prehistoric site contents consist nearly entirely of surface scatters of artifacts, with artifact classes largely the same across each, consisting mainly of debitage, with varying numbers of cores and bifaces. On very few occasions, a preform or utilized flake were also observed. In general, the resources appear to represent raw material procurement areas due to the abundant chert deposits available in the rocky soil. Activities are believed to have been largely limited to the procurement and testing of cobbles and expedient manufacture of bifaces. It appears that more refined tool manufacture was taking place elsewhere. Resources 41NL318, 41TA353/354, 41TA396, and 41TA314 contained the only diagnostic prehistoric artifacts identified during survey. Site 41TA353/354 contained Elam and Carrollton type projectile points and Site 41NL318 contained a Clear Fork Uniface, all of which can date to the middle to transitional Archaic. Sites 41TA396 and 41TA314 each contained a likely Marshall dart point which dates to the Late Middle Archaic. No artifacts were collected. No cultural features or historic-age standing resources were encountered in the field. The resource areas identified within the pipeline survey corridor have been previously disturbed by adjacent pipeline construction. Shovel test results at nearly all permit areas identified subsoils, cemented soils, or bedrock and gave indications of soil deflation or truncating, erosion, and past land modifications such as terracing and grading. Mulberry Creek in Taylor County, Permit Area Number 6, was targeted for deep testing based on geomorphological data, and field results and discussions with the Field Archaeologist. Deep test results indicated a lack of A horizon soils and showed no potential for deeply buried cultural material or paleosols within the anticipated depth of impacts at the location. Based on the overall lack of soil deposition, few diagnostics, and lack of integrity, it is the opinion of Gray & Pape, Inc. that the portions of recorded resources that are located within the proposed right-of- way do not retain the potential to provide significant research value and are thus recommended not eligible for the National Register, under Evaluation Criterion D or for State Antiquities Landmark status. Gray & Pape, Inc. recommends no additional archaeological work for these resources or surveyed permit areas of the project. However, Gray & Pape, Inc. recommends that an unanticipated discoveries plan be put into place in the event that such discoveries take place during construction

Chronic Neurological Impairment in Patients with Thrombotic Thrombocytopenic Purpura: Findings in Quantitative MRI

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening, microvascular blood disorder that affects approximately 5 people per million per year. The disorder is characterized by insufficient activity in ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13), which is an important enzyme in hemostasis because it prevents thrombosis. Along with blood clotting, other predominant symptoms are fever, anaemia, kidney failure, and neurological changes. Neurological changes may include confusion and decreased levels of consciousness, as well as depression and increased risk of seizures or stroke. However, little is known about the general pathology of these neurological changes and this forms the motivation for this research. An observational study using a comprehensive MRI protocol was evaluated in 13 patients and compared to results from assessments of depression and cognition. Despite prolonged remission, there is evidence of persistent neurocognitive decline as manifested in higher scores of depression and widespread white matter lesions