Influence of Talc on the Properties of Silicone Pressure-Sensitive Adhesives.

The article describes new silicone self-adhesive adhesives modified with the addition of talc. The obtained self-adhesive materials were characterized to determine their adhesive properties (adhesion, cohesion, and adhesion) and functional properties (pot life of the composition, shrinkage, and thermal properties of adhesives). Novel materials exhibited high thermal resistance above 225 °C while maintaining or slightly reducing other values (adhesion, cohesion, shrinkage, and tack). Selected composition: T 0.1 was used to prepare self-adhesives in industrial-scale production. Moreover, conducted test results revealed that the addition of talc delayed the thermal decomposition of the adhesive and provided reduced intensity of smoke emissions during combustion as well as the flammability of the adhesive layer.

LRRK2 phosphorylation status and kinase activity regulate (macro)autophagy in a Rab8a/Rab10-dependent manner.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic cause of Parkinson's disease (PD), with growing importance also for Crohn's disease and cancer. LRRK2 is a large and complex protein possessing both GTPase and kinase activity. Moreover, LRRK2 activity and function can be influenced by its phosphorylation status. In this regard, many LRRK2 PD-associated mutants display decreased phosphorylation of the constitutive phosphorylation cluster S910/S935/S955/S973, but the role of these changes in phosphorylation status with respect to LRRK2 physiological functions remains unknown. Here, we propose that the S910/S935/S955/S973 phosphorylation sites act as key regulators of LRRK2-mediated autophagy under both basal and starvation conditions. We show that quadruple LRRK2 phosphomutant cells (4xSA; S910A/S935A/S955A/S973A) have impaired lysosomal functionality and fail to induce and proceed with autophagy during starvation. In contrast, treatment with the specific LRRK2 kinase inhibitors MLi-2 (100 nM) or PF-06447475 (150 nM), which also led to decreased LRRK2 phosphorylation of S910/S935/S955/S973, did not affect autophagy. In explanation, we demonstrate that the autophagy impairment due to the 4xSA LRRK2 phospho-dead mutant is driven by its enhanced LRRK2 kinase activity. We show mechanistically that this involves increased phosphorylation of LRRK2 downstream targets Rab8a and Rab10, as the autophagy impairment in 4xSA LRRK2 cells is counteracted by expression of phosphorylation-deficient mutants T72A Rab8a and T73A Rab10. Similarly, reduced autophagy and decreased LRRK2 phosphorylation at the constitutive sites were observed in cells expressing the pathological R1441C LRRK2 PD mutant, which also displays increased kinase activity. These data underscore the relation between LRRK2 phosphorylation at its constitutive sites and the importance of increased LRRK2 kinase activity in autophagy regulation and PD pathology.

A Correlative Study of Interfacial Segregation in a Cu-Doped TiNiSn Thermoelectric half-Heusler Alloy.

The performance of thermoelectric materials depends on both their atomic-scale chemistry and the nature of microstructural details such as grain boundaries and inclusions. Here, the elemental distribution throughout a TiNiCu0.1Sn thermoelectric material has been examined in a correlative study deploying atom-probe tomography (APT) and electron microscopies and spectroscopies. Elemental mapping and electron diffraction reveal two distinct types of grain boundary that are either topologically rough and meandering in profile or more regular and geometric. Transmission electron microscopy studies indicate that the Cu dopant segregates at both grain boundary types, attributed to extrusion from the bulk during hot-pressing. The geometric boundaries are found to have a degree of crystallographic coherence between neighboring grains; the rough boundaries are decorated with oxide impurity precipitates. APT was used to study the three-dimensional character of rough grain boundaries and reveals that Cu is present as discrete, elongated nanoprecipitates cosegregating alongside larger substoichiometric titanium oxide precipitates. Away from the grain boundary, the alloy microstructure is relatively homogeneous, and the atom-probe results suggest a statistical and uniform distribution of Cu with no evidence for segregation within grains. The extrusion suggests a solubility limit for Cu in the bulk material, with the potential to influence carrier and phonon transport properties across grain boundaries. These results underline the importance of fully understanding localized variations in chemistry that influence the functionality of materials, particularly at grain boundaries.

Atom Probe Tomography of a Cu-Doped TiNiSn Thermoelectric Material: Nanoscale Structure and Optimization of Analysis Conditions.

Cu-doping and crystallographic site occupations within the half-Heusler (HH) TiNiSn, a promising thermoelectric material, have been examined by atom probe tomography. In particular, this investigation aims to better understand the influence of atom probe analysis conditions on the measured chemical composition. Under a voltage-pulsing mode, atomic planes are clearly resolved and suggest an arrangement of elements in-line with the expected HH (F-43m space group) crystal structure. The Cu dopant is also distributed uniformly throughout the bulk material. For operation under laser-pulsed modes, the returned composition is highly dependent on the selected laser energy, with high energies resulting in the measurement of excessively high absolute Ti counts at the expense of Sn and in particular Ni. High laser energies also appear to be correlated with the detection of a high fraction of partial hits, indicating nonideal evaporation behavior. The possible mechanisms for these trends are discussed, along with suggestions for optimal analysis conditions for these and similar thermoelectric materials.

Spatio-temporal focal spot characterization and modeling of the NIF ARC kilojoule picosecond laser.

The advanced radiographic capability (ARC) laser system, part of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory, is a short-pulse laser capability integrated into the NIF. The ARC is designed to provide adjustable pulse lengths of ∼1-38ps in four independent beamlets, each with energies up to 1 kJ (depending on pulse duration). A detailed model of the ARC lasers has been developed that predicts the time- and space-resolved focal spots on target for each shot. Measurements made to characterize static and dynamic wavefront characteristics of the ARC are important inputs to the code. Modeling has been validated with measurements of the time-integrated focal spot at the target chamber center (TCC) at low power, and the space-integrated pulse duration at high power, using currently available diagnostics. These simulations indicate that each of the four ARC beamlets achieves a peak intensity on target of up to a few 1018W/cm2.

National Trends in hospitalizations for self-directed violence related to opioids and/or depression - United States, 2000-2015.

This study examined national trends in self-directed violence in the context of changes in opioid use and depression to better inform prevention measures. Using 2000-2015 National Inpatient Sample (NIS) data, we identified 625,064 hospitalizations for self-directed violence among persons aged ≥10 years in the United States. Based on whether co-listing opioid related diagnosis and depression, we categorized hospitalizations for self-directed violence into four comorbid categories as 1) related to opioids alone; 2) related to depression alone; 3) related to both opioids and depression; and 4) related to neither opioids nor depression. Census population estimates served as the denominator for calculating hospitalization rates for self-directed violence. Hospitalization rates for self-directed violence related to opioids doubled from 5.1 per 100,000 persons in 2000 to 11.0 in 2015. The rate of increase was highest for self-directed violence related to both opioids and depression, which increased 9.4% annually during 2000-2011 and then decreased 4.3% annually during 2011-2015. Hospitalizations for self-directed violence related to depression alone remained the predominant category, accounting for approximately 60% of hospitalizations for self-directed violence; the rates among females aged 10-24 years were the highest among all subgroups, and rose 7.8% annually since 2011 reaching 93.2 per 100,000 persons in 2015. These findings highlight the importance of assessing the risk for self-directed violence among patients misusing opioids and the importance of treating opioid use disorder and depression, particularly when they co-occur. Prevention and treatment of depression is especially important for young females.

Carfentanil Outbreak - Florida, 2016-2017.

Increased prevalence of illicitly manufactured fentanyl and fentanyl analogs has contributed substantially to overdose deaths in the United States (1-3). On October 26, 2015, CDC issued a Health Advisory regarding rapid increases in deaths involving fentanyl. This CDC Health Advisory has been updated twice to address increases in fentanyl and fentanyl analog overdoses and their co-occurrence with nonopioids (4). Deaths involving carfentanil, an analog reportedly 10,000 times more potent than morphine and 100 times more potent than fentanyl, were first reported in Florida, Michigan, and Ohio in 2016 and described in an August 2016 CDC Health Advisory (1,5). Carfentanil is used to rapidly immobilize large animals in veterinary medicine and has no U.S. approved therapeutic use in humans. Carfentanil's street price per dose is likely lower than that of heroin. During 2016 and 2017, an outbreak of carfentanil-involved fatal overdoses in Florida emerged, and the Medical Examiner jurisdiction serving Sarasota, Manatee, and DeSoto counties (the Sarasota area) was the outbreak epicenter. This report describes toxicology profiles, sociodemographic information, and geographic distributions of carfentanil-involved fatal overdoses (carfentanil deaths) in the Sarasota area compared with those in the rest of Florida (i.e., all Florida counties excluding Sarasota area) from January 2016 to December 2017. The Sarasota area accounted for 19.0% of 1,181 statewide carfentanil deaths that occurred during this time and experienced a peak in carfentanil deaths preceding the larger Florida outbreak. The report of a single carfentanil death from August to December 2017 (compared with 73 reported deaths during the same period in 2016) appeared to mark the end of the outbreak in the area. The threat of such rapid, intense fatal overdose outbreaks highlights the need for accelerated reporting, reliable data sharing systems, and novel proactive surveillance to support targeted prevention and response efforts by public health and safety organizations (6).

Opioid Prescribing Behaviors - Prescription Behavior Surveillance System, 11 States, 2010-2016.

PROBLEM/CONDITION: In 2017, a total of 70,237 persons in the United States died from a drug overdose, and 67.8% of these deaths involved an opioid. Historically, the opioid overdose epidemic in the United States has been closely associated with a parallel increase in opioid prescribing and with widespread misuse of these medications. National and state policy makers have introduced multiple measures to attempt to assess and control the opioid overdose epidemic since 2010, including improvements in surveillance systems. PERIOD COVERED: 2010-2016 DESCRIPTION OF SYSTEM: The Prescription Behavior Surveillance System (PBSS) was created in 2011. Its goal was to track rates of prescribing of controlled substances and possible misuse of such drugs using data from selected state prescription drug monitoring programs (PDMP). PBSS data measure prescribing behaviors for prescription opioids using multiple measures calculated from PDMP data including 1) opioid prescribing, 2) average daily opioid dosage, 3) proportion of patients with daily opioid dosages ≥90 morphine milligram equivalents, 4) overlapping opioid prescriptions, 5) overlapping opioid and benzodiazepine prescriptions, and 6) multiple-provider episodes. For this analysis, PBSS data were available for 2010-2016 from 11 states representing approximately 38.0% of the U.S. POPULATION: Average quarterly percent changes (AQPC) in the rates of opioid prescribing and possible opioid misuse measures were calculated for each state. RESULTS AND INTERPRETATION: Opioid prescribing rates declined in all 11 states during 2010-2016 (range: 14.9% to 33.0%). Daily dosage declined least (AQPC: -0.4%) in Idaho and Maine, and most (AQPC: -1.6%) in Florida. The percentage of patients with high daily dosage had AQPCs ranging from -0.4% in Idaho to -2.3% in Louisiana. Multiple-provider episode rates declined by at least 62% in the seven states with available data. Variations in trends across the 11 states might reflect differences in state policies and possible differential effects of similar policies. PUBLIC HEALTH ACTIONS: Use of PDMP data from individual states enables a more detailed examination of trends in opioid prescribing behaviors and indicators of possible misuse than is feasible with national commercially available prescription data. Comparison of opioid prescribing trends among states can be used to monitor the temporal association of national or state policy interventions and might help public health policymakers recognize changes in the use or possible misuse of controlled prescription drugs over time and allow for prompt intervention through amended or new opioid-related policies.

Injection laser system for Advanced Radiographic Capability using chirped pulse amplification on the National Ignition Facility.

We report on the design, performance, and qualification of the injection laser system designed to deliver joule-level chirped pulse beamlets arranged in dual rectangular beam formats into two main laser amplifier beamlines of the National Ignition Facility. The system is designed to meet the requirements of the Advanced Radiographic Capability upgrade with features that deliver performance, adjustability, and long-term reliability.

An Examination of Concurrent Opioid and Benzodiazepine Prescribing in 9 States, 2015.

INTRODUCTION: Concurrent prescribing of opioids and benzodiazepines is discouraged by evidence-based clinical guidelines because of the known risks of taking these medications in combination. METHODS: This study analyzed concurrent opioid and benzodiazepine prescribing in 9 states using the 2015 Prescription Behavior Surveillance System, a multistate database of de-identified prescription drug monitoring program data. Concurrent prescribing rates were examined among individuals with both an opioid and a benzodiazepine prescription. Among patients with concurrent prescribing, total days of opioid supply, daily dosage of opioids, and total days of concurrent prescriptions were examined. Analyses were stratified by whether concurrent prescribing was from a single prescriber or multiple prescribers. Opioid prescribing and concurrent opioid and benzodiazepine prescribing rates were examined by age and sex. Analyses were conducted in 2018. RESULTS: Among 19,977,642 patients that were prescribed an opioid, 21.6% (4,324,092) were also prescribed a benzodiazepine, of which 54.9% (2,375,219) had concurrent prescriptions. More than half of patients with concurrent opioids and benzodiazepines received prescriptions from 2 or more distinct prescribers. Mean total opioid days, daily opioid dosage, and days of concurrent prescribing were higher among patients when multiple prescribers were involved compared with concurrent prescriptions from the same prescriber. Concurrent prescribing was more common among adults aged ≥50 years and female patients. CONCLUSIONS: Public health interventions are needed to reduce concurrent prescribing of opioids and benzodiazepines. Evidence-based guidelines can help reduce concurrent prescribing when one prescriber is involved, and utilization of prescription drug monitoring programs and improved care coordination could help address concurrent prescribing when multiple prescribers are involved.

Effects of mandatory prescription drug monitoring program (PDMP) use laws on prescriber registration and use and on risky prescribing.

BACKGROUND: Comprehensive mandatory use laws for prescription drug monitoring programs (PDMPs) have been implemented in a number of states to help address the opioid overdose epidemic. These laws may reduce opioid-related overdose deaths by increasing prescribers' use of PDMPs and reducing high-risk prescribing behaviors. METHODS: We used state PDMP data to examine the effect of these mandates on prescriber registration, use of the PDMP, and on prescription-based measures of patient risk in three states-Kentucky, Ohio, and West Virginia-that implemented mandates between 2010 and 2015. We conducted comparative interrupted time series analyses to examine changes in outcome measures after the implementation of mandates in the mandate states compared to control states. RESULTS: Mandatory use laws increased prescriber registration and utilization of the PDMP in the mandate states compared to controls. The multiple provider episode rate, rate of opioid prescribing, rate of overlapping opioid prescriptions, and rate of overlapping opioid/benzodiazepine prescriptions decreased in Kentucky and Ohio. Nevertheless, the magnitude of changes in these measures varied among mandates states. CONCLUSIONS: These findings indicate that PDMP mandates have the potential to reduce risky opioid prescribing practices. Variation in the laws may explain why the effectiveness varied between states.

Grain-by-Grain Compositional Variations and Interstitial Metals-A New Route toward Achieving High Performance in Half-Heusler Thermoelectrics.

Half-Heusler alloys based on TiNiSn are promising thermoelectric materials characterized by large power factors and good mechanical and thermal stabilities, but they are limited by large thermal conductivities. A variety of strategies have been used to disrupt their thermal transport, including alloying with heavy, generally expensive, elements and nanostructuring, enabling figures of merit, ZT ≥ 1 at elevated temperatures (>773 K). Here, we demonstrate an alternative strategy that is based around the partial segregation of excess Cu leading to grain-by-grain compositional variations, the formation of extruded Cu "wetting layers" between grains, and-most importantly-the presence of statistically distributed interstitials that reduce the thermal conductivity effectively through point-defect scattering. Our best TiNiCuySn (y ≤ 0.1) compositions have a temperature-averaged ZTdevice = 0.3-0.4 and estimated leg power outputs of 6-7 W cm-2 in the 323-773 K temperature range. This is a significant development as these materials were prepared using a straightforward processing method, do not contain any toxic, expensive, or scarce elements, and are therefore promising candidates for large-scale production.

Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 - 10 States, July-December 2016.

Preliminary estimates of U.S. drug overdose deaths exceeded 60,000 in 2016 and were partially driven by a fivefold increase in overdose deaths involving synthetic opioids (excluding methadone), from 3,105 in 2013 to approximately 20,000 in 2016 (1,2). Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase (3,4). In addition, fentanyl analogs such as acetylfentanyl, furanylfentanyl, and carfentanil are being detected increasingly in overdose deaths (5,6) and the illicit opioid drug supply (7). Carfentanil is estimated to be 10,000 times more potent than morphine (8). Estimates of the potency of acetylfentanyl and furanylfentanyl vary but suggest that they are less potent than fentanyl (9). Estimates of relative potency have some uncertainty because illicit fentanyl analog potency has not been evaluated in humans. This report describes opioid overdose deaths during July-December 2016 that tested positive for fentanyl, fentanyl analogs, or U-47700, an illicit synthetic opioid, in 10 states participating in CDC's Enhanced State Opioid Overdose Surveillance (ESOOS) program.* Fentanyl analogs are similar in chemical structure to fentanyl but not routinely detected because specialized toxicology testing is required. Fentanyl was detected in at least half of opioid overdose deaths in seven of 10 states, and 57% of fentanyl-involved deaths also tested positive for other illicit drugs, such as heroin. Fentanyl analogs were present in >10% of opioid overdose deaths in four states, with carfentanil, furanylfentanyl, and acetylfentanyl identified most frequently. Expanded surveillance for opioid overdoses, including testing for fentanyl and fentanyl analogs, assists in tracking the rapidly changing illicit opioid market and informing innovative interventions designed to reduce opioid overdose deaths.

Opioid Overdose Outbreak - West Virginia, August 2016.

On August 15, 2016, the Mayor's Office of Drug Control Policy in Huntington, West Virginia, notified the Cabell-Huntington Health Department (CHHD) of multiple calls regarding opioid overdose received by the emergency medical system (EMS) during 3 p.m.-8 p.m. that day. A public health investigation and response conducted by the West Virginia Bureau for Public Health (BPH) and CHHD identified 20 opioid overdose cases within a 53-hour period in Cabell County; all cases included emergency department (ED) encounters. EMS personnel, other first responders, and ED providers administered the opioid antidote naloxone to 16 (80%) patients, six of whom were administered multiple doses, suggesting exposure to a highly potent opioid. No patients received referral for recovery support services. In addition to the public health investigation, a public safety investigation was conducted; comprehensive opioid toxicology testing of clinical specimens identified the synthetic opioid fentanyl* and novel fentanyl analogs, including carfentanil,† which had been used by patients who overdosed in Huntington. Results of these two investigations highlight the importance of collaboration between public health and public safety agencies to provide in-depth surveillance data from opioid overdose outbreaks that involve high-potency fentanyl analogs. These data facilitated a public health response through increased awareness of powerful opioid substances requiring multiple naloxone doses for reversal, and improved patient linkage to recovery support services and a harm reduction program from the ED after opioid overdose.

Increases in Fentanyl-Related Overdose Deaths - Florida and Ohio, 2013-2015.

In March and October 2015, the Drug Enforcement Administration (DEA) and CDC issued nationwide alerts identifying fentanyl, particularly illicitly manufactured fentanyl (IMF), as a threat to public health and safety (1,2). IMF is pharmacologically similar to pharmaceutical fentanyl (PF), but is unlawfully produced in clandestine laboratories, obtained via illicit drug markets, and includes fentanyl analogs. Fentanyl is a synthetic opioid 50-100 times more potent than morphine and approved for the management of surgical/postoperative pain, severe chronic pain, and breakthrough cancer pain.* DEA's National Forensic Laboratory Information System (NFLIS) collects drug identification results from drug cases analyzed by federal, state, and local forensic laboratories throughout the United States.(†) In 2014, 80% of fentanyl submissions (i.e., drug products obtained by law enforcement that tested positive for fentanyl) in NFLIS were identified from 10 states, including Florida and Ohio (2), and seven of these 10 states reported sharp increases in fentanyl-related overdose deaths (fentanyl deaths) (3). This report presents findings of increased fentanyl deaths during 2013-2015 from investigations conducted by the University of Florida and the Ohio Department of Public Health, in collaboration with CDC. Analyses examined the association between trends in fentanyl-related law enforcement submissions and fentanyl deaths and describes groups at risk for fentanyl death using medical examiner and coroner reports. The marked increases in fentanyl death in Florida and Ohio during 2013-2015 were closely associated with parallel increases in fentanyl submissions, with the largest impact on persons who use heroin, consistent with reports that IMF is commonly mixed with or sold as heroin (1,4). In Ohio, circumstances associated with fentanyl deaths included a current diagnosed mental health disorder(§) and recent release from an institution such as a jail, rehabilitation facility, or hospital.

Laser-vibrometric ultrasonic characterization of resonant modes and quality factors of Ge membranes.

The vibrations of a single-crystal germanium (Ge) membrane are studied in air and vacuum using laser vibrometry, in order to determine mechanical properties such as Q-factors, tensile stress, anisotropy, and robustness to shock. Resonance modes up to 3:2 are identified, giving a residual stress measurement of 0.22 GPa, consistent with the value obtained from x-ray relaxation studies. The membrane is found to be isotropic, with Q-factors ranging from around 40 at atmospheric pressure to over 3200 at [Formula: see text] mbar, significantly lower than those found in polycrystalline Ge micromechanical devices. The robustness to shock is explained through the high resonance mode frequencies and the dissipation mechanism into the substrate, which is a direct consequence of having a high quality film with low residual tensile stress, giving the potential for such films to be used in optoelectronic devices.

Characterization of SiGe thin films using a laboratory X-ray instrument.

The technique of reciprocal space mapping using X-rays is a recognized tool for the nondestructive characterization of epitaxial films. X-ray scattering from epitaxial Si0.4Ge0.6 films on Si(100) substrates using a laboratory X-ray source was investigated. It is shown that a laboratory source with a rotating anode makes it possible to investigate the material parameters of the super-thin 2-6 nm layers. For another set of partially relaxed layers, 50-200 nm thick, it is shown that from a high-resolution reciprocal space map, conditioned from diffuse scattering on dislocations, it is possible to determine quantitatively from the shape of a diffraction peak (possessing no thickness fringes) additional parameters such as misfit dislocation density and layer thickness as well as concentration and relaxation.

A decision process for determining whether to conduct responder health research following large disasters.

Disasters often set the stage for scientific inquiry within the field of occupational safety and health. This is especially true when the long-term consequences of exposures associated with a particular disaster are unclear. However, a responder research study can be costly and difficult to design, and researchers must consider whether the proposed study will produce useful, reliable results and is a prudent public health investment. The decision process can be segregated into various components, including scientific rationale that should be formally recognized as critical to efficiently and effectively determine whether a research study is warranted. The scientific rationale includes certain controlling or "gatekeeper" factors that should be present to proceed with research.

Recommendations for biomonitoring of emergency responders: focus on occupational health investigations and occupational health research.

The disaster environment frequently presents rapidly evolving and unpredictable hazardous exposures to emergency responders. Improved estimates of exposure and effect from biomonitoring can be used to assess exposure-response relationships, potential health consequences, and effectiveness of control measures. Disaster settings, however, pose significant challenges for biomonitoring. A decision process for determining when to conduct biomonitoring during and following disasters was developed. Separate but overlapping decision processes were developed for biomonitoring performed as part of occupational health investigations that directly benefit emergency responders in the short term and for biomonitoring intended to support research studies. Two categories of factors critical to the decision process for biomonitoring were identified: Is biomonitoring appropriate for the intended purpose and is biomonitoring feasible under the circumstances of the emergency response? Factors within these categories include information needs, relevance, interpretability, ethics, methodology, and logistics. Biomonitoring of emergency responders can be a valuable tool for exposure and risk assessment. Information needs, relevance, and interpretability will largely determine if biomonitoring is appropriate; logistical factors will largely determine if biomonitoring is feasible. The decision process should be formalized and may benefit from advance planning.