Status of document search and data quality objective efforts

The purpose of this letter report is to document the status of the identification, search, retrieval, evaluation, declassification and availability of (1) Hanford-Site-originated operating information necessary to reconstruct radiation doses and (2) monitoring information indicating concentrations of radioactive materials in the environment. All information needed to date to reconstruct the radiation doses has been identified, sought, retrieved, evaluated, declassified, and made available. Any data needed in the future that have not yet been found will be sought using the same search tree method used to identify the Hanford-Site-originated documents up to now. This search tree method has ensured that the data quality objective of completeness is met. Because there was a centralized list of documents for which we have technical indices the documents through 1964 have been identified, and the document collections are considered as complete as possible. The collection of documents from 1965--1972 is complete for monthly average data but not to the same extent as for the years 1944--1964 where daily and sometimes hourly data are often available and for which a subject index is readily available. From 1965--1972 there were multiple contractors, each maintaining a separate document system with no detailed subject index for retrieval purposes. A HEDR Information Resources Tracking System (HIRTS) database has been established of all documents identified as being of potential interest and/or use to dose reconstruction. The HIRTS contains more than 6000 citations with bibliographic information on each report, document number(s), author(s), title, date, document form (hard copy or microfilm), number of pages, location, public availability, and names of HEDR Project and TSP staff who have requested copies

Letter report: Title listing of daily operating data on Hanford single-pass reactors, 1944--1971. Hanford Environmental Dose Reconstruction Project

The primary objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation dose that populations and individuals could have received as a result of emissions from Hanford Site operations since 1944, with descriptions of the uncertainties inherent in such estimates. A secondary objective is to make project documentation and Hanford-originated references used in the reports available to the public. Hanford-originated documents of potential interest and/or use to the HEDR Project are made publicly available through the US Government`s National Technical Information Service and placed in the US Department of Energy Richland Field Office (RL) Public Reading Room in Richland, Washington. Project work is conducted under several technical tasks, among which is the Source Terms Task. Under this task, estimates of radioactive emissions from Hanford facilities since 1944 are developed. These estimates are based on historical measurements and production information. The Information Resources Task identifies and retrieves historical production operating information for developing source terms. The purpose of this letter report is to identify documents that record daily reactor operating information at the Hanford Site for the years 1944--1971. Complete bibliographic citations and sample pages from each different format for Hanford reactor operations data are included

Rates and predictors of hypoglycaemia in 27 585 people from 24 countries with insulin-treated type 1 and type 2 diabetes : the global HAT study

Aims: To determine the global extent of hypoglycaemia experienced by patients with diabetes using insulin, as there is a lack of data on the prevalence of hypoglycaemia in developed and developing countries. Methods: This non-interventional, multicentre, 6-month retrospective and 4-week prospective study using self-assessment questionnaire and patient diaries included 27 585 patients, aged >= 18 years, with type 1 diabetes (T1D; n = 8022) or type 2 diabetes (T2D; n = 19 563) treated with insulin for > 12 months, at 2004 sites in 24 countries worldwide. The primary endpoint was the proportion of patients experiencing at least one hypoglycaemic event during the observational period. Results: During the prospective period, 83.0% of patients with T1D and 46.5% of patients with T2D reported hypoglycaemia. Rates of any, nocturnal and severe hypoglycaemia were 73.3 [95% confidence interval (CI) 72.6-74.0], 11.3 (95% CI 11.0-11.6) and 4.9 (95% CI 4.7-5.1) events/patient-year for T1D and 19.3 (95% CI 19.1-19.6), 3.7 (95% CI 3.6-3.8) and 2.5 events/patient-year (95% CI 2.4-2.5) for T2D, respectively. The highest rates of any hypoglycaemia were observed in Latin America for T1D and Russia for T2D. Glycated haemoglobin level was not a significant predictor of hypoglycaemia. Conclusions: We report hypoglycaemia rates in a global population, including those in countries without previous data. Overall hypoglycaemia rates were high, with large variations between geographical regions. Further investigation into these differences may help to optimize therapy and reduce the risk of hypoglycaemia.Peer reviewe

The genetics and neuropathology of frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) is a heterogeneous group of disorders characterized by disturbances of behavior and personality and different types of language impairment with or without concomitant features of motor neuron disease or parkinsonism. FTLD is characterized by atrophy of the frontal and anterior temporal brain lobes. Detailed neuropathological studies have elicited proteinopathies defined by inclusions of hyperphosphorylated microtubule-associated protein tau, TAR DNA-binding protein TDP-43, fused-in-sarcoma or yet unidentified proteins in affected brain regions. Rather than the type of proteinopathy, the site of neurodegeneration correlates relatively well with the clinical presentation of FTLD. Molecular genetic studies identified five disease genes, of which the gene encoding the tau protein (MAPT), the growth factor precursor gene granulin (GRN), and C9orf72 with unknown function are most frequently mutated. Rare mutations were also identified in the genes encoding valosin-containing protein (VCP) and charged multivesicular body protein 2B (CHMP2B). These genes are good markers to distinguish underlying neuropathological phenotypes. Due to the complex landscape of FTLD diseases, combined characterization of clinical, imaging, biological and genetic biomarkers is essential to establish a detailed diagnosis. Although major progress has been made in FTLD research in recent years, further studies are needed to completely map out and correlate the clinical, pathological and genetic entities, and to understand the underlying disease mechanisms. In this review, we summarize the current state of the rapidly progressing field of genetic, neuropathological and clinical research of this intriguing condition

Hanford Site Process Flow Diagrams, 1958

This report consists of flow diagrams extracted from the General Managers Data Book and prepared as a separate document that graphically depicts in lay language the site operation in 1958. (JL

Declassifications requested by the Technical Steering Panel of Hanford documents produced 1944--1960

The purpose of this letter report is to list the actions taken on historical documents that the Technical Steering Panel (TSP) and/or the public identified as being of potential use to the Hanford Environmental Dose Reconstruction (HEDR) Project. The documents addressed herein were generated from 1944 through 1960 at the Hanford Site and were still listed as classified documents in 1990. This report lists the 1429 documents and their classification status. All TSP- and/or public-requested declassifications of Hanford historical documents generated from 1944--1960 have been completed. Of the 1429 documents, 1103 were declassified. (492 as a result of TSP/public requests, 506 previously declassified, 105 declassified for other programs). The remaining 326 documents were not declassified because either they were determined by the TSP to be not applicable to the HEDR Project or because of the reasons given in the appendixes. Of the 1103 declassified documents, 506 have not been reviewed by the TSP for their pertinence to the HEDR Project. Figure I provides an overview of the declassification process

Exclusion mapping in familial non-specific dementia

We present genetic linkage data in a large family in which non-specific dementia is inherited as an autosomal dominant trait. We have analyzed 45 highly polymorphic microsatellite sequences and excluded a quarter of the genome as the site of the pathogenic mutation in this family

Performance of claims-based algorithms for identifying incident thyroid cancer in commercial health plan enrollees receiving antidiabetic drug therapies

Background: Thyroid cancer incidence is increasing in the United States (US) and many other countries. The objective of this study was to develop and evaluate algorithms using administrative medical claims data for identification of incident thyroid cancer. Methods: This effort was part of a prospective cohort study of adults initiating therapy on antidiabetic drugs and used administrative data from a large commercial health insurer in the US. Patients had at least 6 months of continuous enrollment prior to initiation during 2009–2013, with follow-up through March, 2014 or until disenrollment. Potential incident thyroid cancers were identified using International Classification of Diseases, 9th Revision (ICD-9) diagnosis code 193 (malignant neoplasm of the thyroid gland). Medical records were adjudicated by a thyroid cancer specialist. Several clinical variables (e.g., hospitalization, treatments) were considered as predictors of case status. Positive predictive values (PPVs) and 95% confidence intervals (CIs) were calculated to evaluate the performance of two primary algorithms. Results: Charts were requested for 170 patients, 150 (88%) were received and 141 (80%) had sufficient information to adjudicate. Of the 141 potential cases identified using ≥1 ICD-9 diagnosis code 193, 72 were confirmed as incident thyroid cancer (PPV of 51% (95% CI 43–60%)). Adding the requirement for thyroid surgery increased the PPV to 68% (95% CI 58-77%); including the presence of other therapies (chemotherapy, radio-iodine therapy) had no impact. When cases were required to have thyroid surgery during follow-up and ≥2 ICD-9 193 codes within 90 days of this surgery, the PPV was 91% (95% CI 81-96%); 62 (82%) of the true cases were identified and 63 (91%) of the non-cases were removed from consideration by the algorithm as potential cases. Conclusions: These findings suggest a significant degree of misclassification results from relying only on ICD-9 diagnosis codes to detect thyroid cancer. An administrative claims-based algorithm was developed that performed well to identify true incident thyroid cancer cases