Pathogenic Variants in Fucokinase Cause a Congenital Disorder of Glycosylation

FUK encodes fucokinase, the only enzyme capable of converting L-fucose to fucose-1-phosphate, which will ultimately be used for synthesizing GDP-fucose, the donor substrate for all fucosyltransferases. Although it is essential for fucose salvage, this pathway is thought to make only a minor contribution to the total amount of GDP-fucose. A second pathway, the major de novo pathway, involves conversion of GDP-mannose to GDP-fucose. Here we describe two unrelated individuals who have pathogenic variants in FUK and who presented with severe developmental delays, encephalopathy, intractable seizures, and hypotonia. The first individual was compound heterozygous for c.667T>C (p.Ser223Pro) and c.2047C>T (p.Arg683Cys), and the second individual was homozygous for c.2980A>C (p.Lys994Gln). Skin fibroblasts from the first individual confirmed the variants as loss of function and showed significant decreases in total GDP-[3H] fucose and [3H] fucose-1-phosphate. There was also a decrease in the incorporation of [5,6-3H]-fucose into fucosylated glycoproteins. Lys994 has previously been shown to be an important site for ubiquitin conjugation. Here, we show that loss-of-function variants in FUK cause a congenital glycosylation disorder characterized by a defective fucose-salvage pathway

Gemcitabine and Irinotecan for Patients with Untreated Extensive Stage Small Cell Lung Cancer: SWOG 0119

IntroductionTo evaluate the activity of a nonplatinum-, nonetoposide-containing regimen for patients with extensive stage small cell lung cancer.MethodsPatients with untreated extensive stage small cell lung cancer were treated with gemcitabine 1000 mg/m2 and irinotecan 100 mg/m2 on days 1 and 8 of a 21-day cycle for a maximum of six cycles. Patients with brain metastases were eligible if asymptomatic or controlled after radiation.ResultsEighty-four eligible patients with untreated extensive stage small cell lung cancer with adequate organ function and a performance status of 0–2 were accrued. The median age was 64 years (range, 42–85) and 45 (54%) were women. Six cycles were completed by 28 (33%) patients. Some degree of diarrhea occurred in 57% (grade 3/4, 18%). Other grade 3/4 toxicities were neutropenia (26%), anemia (10%), thrombocytopenia (8%), febrile neutropenia (5%), fatigue (11%), nausea (10%), and vomiting (8%). The response rate was 32% (95% confidence interval: 22%–43%) among the 81 patients with measurable disease. The median survival was 8.5 months (95% confidence interval: 7.0–9.8) with 1- and 2-year survival rates of 26% and 7%, respectively. Salvage therapy data were captured by prospective collection, and only 50% of patients were treated secondarily.ConclusionThe overall response rate with the combination of gemcitabine and irinotecan was disappointing, and the median survival rate was lower than expected. Further development of this combination in small cell lung cancer is not recommended

Republic of the Marshall Islands Changed Circumstances Petition to Congress

This report summarizes U.S. nuclear testing on the Marshall Islands, U.S. compensation efforts to date, relevant provisions in the Compact of Free Association, and the Changed Circumstances Petition. It analyzes several issues related to the personal injury, health care, and property damages claims in the Petition

Quality assurance and quality control processes:summary of a metabolomics community questionnaire

Introduction The Metabolomics Society Data Quality Task Group (DQTG) developed a questionnaire regarding quality assurance (QA) and quality control (QC) to provide baseline information about current QA and QC practices applied in the international metabolomics community. Objectives The DQTG has a long-term goal of promoting robust QA and QC in the metabolomics community through increased awareness via communication, outreach and education, and through the promotion of best working practices. An assessment of current QA and QC practices will serve as a foundation for future activities and development of appropriate guidelines. Method QA was defined as the set of procedures that are performed in advance of analysis of samples and that are used to improve data quality. QC was defined as the set of activities that a laboratory does during or immediately after analysis that are applied to demonstrate the quality of project data. A questionnaire was developed that included 70 questions covering demographic information, QA approaches and QC approaches and allowed all respondents to answer a subset or all of the questions. Result The DQTG questionnaire received 97 individual responses from 84 institutions in all fields of metabolomics covering NMR, LC-MS, GC-MS, and other analytical technologies. Conclusion There was a vast range of responses concerning the use of QA and QC approaches that indicated the limited availability of suitable training, lack of Standard Operating Procedures (SOPs) to review and make decisions on quality, and limited use of standard reference materials (SRMs) as QC materials. The DQTG QA/QC questionnaire has for the first time demonstrated that QA and QC usage is not uniform across metabolomics laboratories. Here we present recommendations on how to address the issues concerning QA and QC measurements and reporting in metabolomics

Two-Proton Correlations from 14.6A GeV/c Si+Pb and 11.5A GeV/c Au+Au Central Collisions

Two-proton correlation functions have been measured in Si+Pb collisions at 14.6A GeV/c and Au+Au collisions at 11.5A GeV/c by the E814/E877 collaboration. Data are compared with predictions of the transport model RQMD and the source size is inferred from this comparison. Our analysis shows that, for both reactions, the characteristic size of the system at freeze-out exceeds the size of the projectile, suggesting that the fireball created in the collision has expanded. For Au+Au reactions, the observed centrality dependence of the two-proton correlation function implies that more central collisions lead to a larger source sizes.Comment: RevTex, 12 pages, 5 figure

Use of electronic health record data to identify skin and soft tissue infections in primary care settings: a validation study

Background: Epidemiologic studies of skin and soft tissue infections (SSTIs) depend upon accurate case identification. Our objective was to evaluate the positive predictive value (PPV) of electronic medical record data for identification of SSTIs in a primary care setting. Methods: A validation study was conducted among primary care outpatients in an academic healthcare system. Encounters during four non-consecutive months in 2010 were included if any of the following were present in the electronic health record: International Classification of Diseases, Ninth Revision (ICD-9) code for an SSTI, Current Procedural Terminology (CPT) code for incision and drainage, or a positive wound culture. Detailed chart review was performed to establish presence and type of SSTI. PPVs and 95% confidence intervals (CI) were calculated among all encounters, initial encounters, and cellulitis/abscess cases. Results: Of the 731 encounters included, 514 (70.3%) were initial encounters and 448 (61.3%) were cellulitis/abscess cases. When the presence of an ICD-9 code, CPT code, or positive culture was used to identify SSTIs, 617 encounters were true positives, yielding a PPV of 84.4% [95% CI: 81.8–87.0%]. The PPV for using ICD-9 codes alone to identify SSTIs was 90.7% [95 % CI: 88.5–92.9%]. For encounters with cellulitis/abscess codes, the PPV was 91.5% [95% CI: 88.9–94.1%]. Conclusions: ICD-9 codes may be used to retrospectively identify SSTIs with a high PPV. Broadening SSTI case identification with microbiology data and CPT codes attenuates the PPV. Further work is needed to estimate the sensitivity of this method.Keywords: Skin infection, Positive predictive value, Methodologies, Abscess, Primary careKeywords: Skin infection, Positive predictive value, Methodologies, Abscess, Primary car

RHIC physics overview

The results from data taken during the last several years at the Relativistic Heavy-Ion Collider (RHIC) will be reviewed in the paper. Several selected topics that further our understanding of constituent quark scaling, jet quenching and color screening effect of heavy quarkonia in the hot dense medium will be presented. Detector upgrades will further probe the properties of Quark Gluon Plasma. Future measurements with upgraded detectors will be presented. The discovery perspectives from future measurements will also be discussed.Comment: 9 pages, 4 figures, invited review article, published by Frontier of Physics in Chin

Frequency of Outpatient Antibiotic Prescription on Discharge to Hospice Care

The use of antibiotics is common in hospice care despite limited evidence that it improves symptoms or quality of life. Patients receiving antibiotics upon discharge from a hospital may be more likely to continue use following transition to hospice care despite a shift in the goals of care. We quantified the frequency and characteristics for receiving a prescription for antibiotics on discharge from acute care to hospice care. This was a cross-sectional study among adult inpatients (≥18 years old) discharged to hospice care from Oregon Health & Science University (OHSU) from 1 January 2010 to 31 December 2012. Data were collected from an electronic data repository and from the Department of Care Management. Among 62,792 discharges, 845 (1.3%) patients were discharged directly to hospice care (60.0% home and 40.0% inpatient). Most patients discharged to hospice were >65 years old (50.9%) and male (54.6%) and had stayed in the hospital for ≤7 days (56.6%). The prevalence of antibiotic prescription upon discharge to hospice was 21.1%. Among patients discharged with an antibiotic prescription, 70.8% had a documented infection during their index admission. Among documented infections, 40.3% were bloodstream infections, septicemia, or endocarditis, and 38.9% were pneumonia. Independent risk factors for receiving an antibiotic prescription were documented infection during the index admission (adjusted odds ratio [AOR]=7.00; 95% confidence interval [95% CI]=4.68 to 10.46), discharge to home hospice care (AOR=2.86; 95% CI=1.92 to 4.28), and having a cancer diagnosis (AOR=2.19; 95% CI=1.48 to 3.23). These data suggest that a high proportion of patients discharged from acute care to hospice care receive an antibiotic prescription upon discharge

109th Congress

Environmental protection concerns span a wide variety of issues, including clean air, water quality, chemical security, and environmental aspects of other major issue areas, such as energy, transportation, disaster relief and cleanup, and defense. This report provides an overview of key environmental issues receiving attention in the 109th Congress