Recommendations on data sharing in HIV drug resistance research

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens.  • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens.  • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines.  • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing.  • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions.  • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Combination leflunomide and methotrexate (MTX) therapy for patients with active rheumatoid arthritis failing MTX monotherapy: open-label extension of a randomized, double-blind, placebo controlled trial

P e r s o n a l n o n -c o m m e r c i a l u s e o n l y . T h e J o u r n a l o f R h e u m a t o l o g y . C o p y r i g h t © 2 0 0 4 . A l l r i g h t s r e s e r v e d Conclusion. Response to therapy was maintained to 48 weeks of treatment in patients who continued to receive LEF and MTX during the extension. Importantly, ACR20 response rates after 24 weeks of LEF therapy were similar between patients switched from PLA to LEF without loading dose, and those who received a loading does of LEF (100 mg/day × 2 days) at randomization. Fewer adverse events were reported in patients switched to LEF without a loading dose. (J Rheumatol 2004;31:1521-31

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The Ruby cover-up /

Originally published by Everest House, New York, under title: Who was Jack Ruby?Includes bibliographical references (pages 439-441) and index.Los foxes and el songbird -- The private government of Jack Ruby -- The weekend -- A stillness on the fifth floor -- Any friend of Needle-Nose Labriola -- Put that in your pipe and smoke it -- In search of class -- Cuba -- The ring of bulls -- An amicable solution -- May Day -- Man's best friend -- The truth, the whole truth and other fables -- Faster than a speeding magic bullet -- A matter of conspiracy

The rise in non-fatal and fatal overdoses involving stimulants with and without opioids in the United States.

AIMS: To examine trends and recent changes in non-fatal and fatal stimulant overdose rates with and without opioids to improve the descriptive characterization of the US overdose epidemic. DESIGN: Secondary analysis of non-fatal (2006-16) and fatal (2006-17) drug overdose trends, focusing on the most recent years of data available to examine rate changes by demographics (2015-16 for non-fatal and 2016-17 for fatal). SETTING: Non-fatal drug overdoses from the Healthcare Cost and Utilization Project's Nationwide Emergency Department Sample; drug overdose deaths from the National Vital Statistics System. PARTICIPANTS/CASES: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and Tenth Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS) codes for cocaine, psychostimulants and opioids were used to classify non-fatal drug overdoses. Drug overdose deaths were identified using ICD-10 multiple cause-of-death codes for cocaine, psychostimulants, all opioids, heroin and synthetic opioids. MEASUREMENTS: Percentage of changes in age-adjusted non-fatal and fatal rates of cocaine and psychostimulant-involved drug overdose with and without opioids. FINDINGS: Overall, cocaine-involved non-fatal overdose rates with an opioid increased from 2006 to 2016 [annual percentage change (APC) = 14.7], while rates without an opioid increased from 2006 to 2012 (APC = 11.3) and then remained stable (APC = -7.5). Psychostimulant-involved non-fatal rates with and without an opioid increased from 2006 to 2016 (APC = 49.9 with opioids; 13.9 without opioids). Cocaine-involved death rates with and without opioids increased from 2014 to 2017 (APC = 46.0 with opioids, 23.6 without opioids). Psychostimulant-involved death rates with opioids increased from 2010 to 2015 (APC = 28.6), with a dramatic increase from 2015 to 2017 (APC = 50.5), while rates without opioids increased from 2008 to 2017 (APC = 22.6). In 2016, 27% of non-fatal cocaine- and 14% of psychostimulant-involved overdoses included a reported opioid; 72.7% of cocaine- and 50.3% of psychostimulant-involved deaths involved an opioid in 2017. From 2015 to 2016, cocaine-involved and psychostimulant-involved non-fatal overdose rates with an opioid increased 17.0 and 5.9%, respectively; cocaine-involved and psychostimulant-involved non-fatal overdoses without opioids decreased 13.6 and increased 18.9%, respectively. Death rates involving stimulants increased with and without opioids from 2016 to 2017 (cocaine with and without opioids = 37.7 and 23.3%; psychostimulants with and without opioids = 52.2 and 23.0%). Death rates involving stimulants with synthetic opioids increased dramatically from 2016 to 2017 (1.3-2.3 per 100 000 for cocaine and 0.3-0.8 for psychostimulants). CONCLUSIONS: While increases in cocaine-involved deaths in the United States from 2006 seem to be driven by opioids, particularly synthetic opioids, increases in non-fatal and fatal overdoses involving psychostimulants are occurring with and without opioids

Trends in Suspected Opioid Overdoses from Emergency Departments in 11 States and DC

ObjectiveThis presentation will provide insight into how the extensive spread of illicitly-manufactured fentanyl impacted opioid overdose rates throughout the Midwest and neighboring states.IntroductionRecent reporting using data from CDC’s National Syndromic Surveillance Program indicates that rates of emergency department (ED) visits involving suspected opioid overdoses increased by 70% in the Midwest from the third quarter (Q3) 2016 (July–September) to the Q3 2017. Large increases in the use and distribution of illicitly-manufactured fentanyl (IMF) and fentanyl analogs, are a key factor driving increased opioid overdose rates in the Midwest and east of the Mississippi River. Fentanyl is a synthetic opioid 50–100 times more potent than morphine. A better understanding of the distribution of changes in opioid overdose rate from Q3 2016 to Q3 2017 within states needed to inform response and prevention efforts.MethodsThe CDC’s Enhanced State Opioid Overdose Surveillance Program currently funds 32 states and Washington DC to increase timeliness of opioid overdose reporting and detect rapid changes in trends. Data from nine states (IL, MD, MO, NC, OH, PA, VA, WI, WV) were analyzed. Midwest states sharing subregional data with CDC were selected to better understand geographic and temporal patterns driving previously reported increases in ED visits involving suspected opioid overdoses from Q3 2016 through Q3 2017. Bordering states (MD, NC, PA, VA, WV) sharing subregional data with CDC were also included to determine trends in states contiguous to the Midwest. State subregions were defined using publicly available state government sources in consultation with state public health departments and were mainly divided by public health districts. . Fifty of 56 possible state subregions across 9 states met two inclusion criteria: 1) reported 25 opioid overdose ED visits per quarter and 2) did not report a change of 50% between any two quarters. Opioid overdoses were defined according to jurisdictional and national definitions that included searches of chief complaint text (e.g., searching for words “opioid” and “overdose”) and ICD-10-CM diagnostic/billing codes. State subregional rates were defined as number of opioid overdoses divided by the total number of ED visits in the state subregion, multiplied by 10,000. Quarterly and yearly percent change in opioid overdose ED visits from Q3 2016 to Q3 2017 were described with a focus on high burden subregions reporting large yearly increases of 25% from Q3 2016 to Q3 2017. We categorized a subregion as having an opioid overdose outbreak when at least one quarterly rate increase in opioid overdoses of 50% occurred.ResultsOver 7 million ED visits were reported each quarter. Average subregional opioid overdose rates increased at a consistent quarterly rate of between 16% - 19% during Q3 2016 to Q2 2017. From Q2 2017 to Q3 2017, opioid overdose rates only increased 1%. Overall, subregions reported a mean yearly increase in opioid overdose rates of 51% from Q3 2016 to Q3 2017. This yearly increase in opioid overdose from Q3 2016 to Q3 2017 was unequally distributed across subregions with 9 (18%) of subregions reporting an increase in opioid overdose rates of 100%, 13 (26%) reporting an increase of 50% - &lt;100%, 7 (14%) reporting an increase of 25% - &lt;50%, 13 (26%) reporting an increases of 0% to &lt;25%, and 8 (16%) reporting a decrease. Analyses of the 29 high burden subregions found that 16 (55%) reported at least one opioid overdose outbreak compared to 3 of 21 other subregions (14%) (Table 1). The 16 high burden subregions that reported any outbreak had a mean yearly increase in opioid overdose rates from Q3 2016 to Q3 2017 of 107%, range 33% to 266%. Eight of these 16 high burden subregions either reported two opioid overdose outbreaks or an opioid overdose outbreak and a quarterly increase of between 25% - &lt;50%.All states had at least one subregion report an opioid overdose outbreak between Q3 2016 to Q2 2017. Also, within OH, PA, WI, and WV, half or more of their subregions reported an outbreak between Q3 2016 and Q3 2017 (Table 1). Fifteen of the 22 (68%) quarterly opioid overdose outbreaks occurred either during Q4 2016 or Q1 2017 (Table 1). Across all outbreaks, state subregions reported a mean quarterly increase of 83% with a range from 50 - 156%.ConclusionsOpioid overdose outbreaks in a subset of 16 high burden subregions across all 9 states were a key factor driving increases in the states’ opioid overdose rates. Half of these 16 subregions experienced a single opioid overdose outbreak while the other half experienced two or more sharp increases. The majority of opioid overdose outbreaks occurred during October 2016 to March 2017 were concentrated in Ohio, a state reporting extremely large increase in IMF supply and overdose deaths involving fentanyl, and states contiguous with Ohio. Although most subregions reported outbreaks at the beginning of the study period, higher opioid overdose rates persisted in the vast majority of subregions reporting opioid overdose outbreaks. This outbreak pattern is consistent with previous findings showing large increases in the supply of IMF and fentanyl analogs, including carfentanil, in Midwestern states during 2016 and in early 2017. Although opioid overdose outbreaks were concentrated in subregions in OH, PA, and WV, all 9 states included in the analysis were impacted by at least one outbreak during the study period. Findings highlight the need for targeting of hotspots within states and implementation of public health interventions to reduce harm and surge resources during an outbreak. These short-term efforts, however, must be complemented by a sustained response to reduce increased drug overdose rates that persist after an initial outbreak. A key limitation of this study was that it only included data from a single year and as a result may underestimate the length and severity of outbreaks. As changes in the illicit opioid market continue, surveillance of local outbreaks must be supplemented by broader surveillance designed to detect both localized introduction of new novel psychoactive substances as well as large scale changes in the illicit opioid market.ReferencesVivolo-Kantor, A. M., Seth, P., Gladden, R.M., et al. (2018). Vital Signs: Trends in Emergency Department Visits for Suspected Opioid Overdoses—United States, July 2016–September 2017.Morbidity and Mortality Weekly Report, 67, 279-285.O’Donnell J, Gladden RM, Mattson CL, et al. Notes from the Field: Overdose Deaths with Carfentanil and Other Fentanyl Analogs Detected — 10 States, July 2016–June 2017. Morb Mortal Wkly Rep 2018;67:767–768.O’Donnell JK, Halpin J, Mattson CL, et al. Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 — 10 States, July–December 2016. Morb Mortal Wkly Rep 2017;66:1197–1202.