Sleep, alcohol, and caffeine in financial traders.

Alcohol and caffeine are two of the most commonly used substances for altering human consciousness. While their adverse effects on sleep have been separately examined in the laboratory and epidemiological levels, how they impact real-world night-to-night sleep, in isolation or together, remains unclear. This is especially true in occupations wherein the use of alcohol and caffeine is high (e.g., financial services sector). Using a six-week micro-longitudinal study, here we examined the real-world impact of alcohol, caffeine, and their combined consumption in a cohort of financial traders. We demonstrate that alcohol consumption significantly degrades the subjective quality of sleep (p < 0.001). Caffeine consumption led to a different phenotype of sleep impairment, resulting in a detrimental reduction in sleep quantity (p = 0.019), rather than a marked alteration in sleep quality. Contrary to our hypothesis, when consumed in combination, evening alcohol consumption interacted with ongoing caffeine consumption such that alcohol partially mitigated the impairments in sleep quantity associated with caffeine (p = 0.032). This finding suggests the sedating effects of alcohol and the psychoactive stimulant effects of caffeine obscure each other's impact on sleep quantity and sleep quality, respectively-potentially explaining their interdependent use in this cohort (i.e., "self-medication" of evening sedation with alcohol to combat the prior daytime ingestion of caffeine and vice versa). More generally, these results contribute to a unique understanding of the singular and combinatory impacts of two of the most commonly used substances for augmenting human consciousness under free-living, real-world conditions, the performance-impairing (and thus economic-cost) consequences of which may be important to the business sector and the society.

Clinician Opinions: Perceived Utility of and Barriers to Incorporating Pretreatment Ecological Momentary Assessment Into Clinical Care.

Increasingly, clinicians have the option of including technological components into clinical care. However, little research has assessed clinicians' interest in utilizing technology in their clinical work. Here, clinicians reported their opinions related to using a mobile assessment platform (MAP) to collect ecological data from clients before providing clinical care. Practicing and training mental health clinicians (N = 221) reported demographics, characteristics of their clinical work, and confidence in their clinical skill. Participants then read a description of MAP and responded to questions about their perceived benefits of and barriers to its use. Last, participants rated their interest in using MAP in their clinical work. These perceptions were then factor-analyzed and the resulting factor scores were regressed onto clinician characteristics. Interest in using MAP was significantly lower for the group that endorsed a psychodynamic/psychoanalytic orientation and those with greater confidence in their clinical skills. Across scales, we found a pattern that participants who did not identify as male, those with a psychodynamic/psychoanalytic orientation, and those with greater confidence in their clinical skills tended to have lower ratings of the benefits of and higher ratings for the barriers to using MAP. Results revealed that significant differences in opinions about incorporating technology into clinical work exist between different groups of clinicians. This information may be useful in future work that attempts to implement technological tools into clinical settings.

Posttraumatic stress symptoms and substance use among college students: Exploring interactions with sleep quality and assigned sex.

Substance use is widely recognized as a negative outcome following traumatic events and is tied to symptoms of posttraumatic stress (PTS). Sleep quality may influence the PTS and substance use association, particularly among college students who are at risk for poor sleep. The purpose of the present study was to examine the moderating effect of sleep quality on the relationship between PTS and substance use in a cohort of college students, with an exploratory aim of examining potential differences by assigned sex. A screening survey was completed by 2,767 students enrolled in a larger RCT examining various brief college student alcohol reduction strategies. Results found a significant two-way interaction between PTS symptoms and subjective sleep quality on weekly number of drinks and peak drinking occasion, where the significant positive association between PTS symptoms to weekly drinks and peak drinking occasion was only found for those who reported poor sleep quality. A similar pattern emerged for the significant two-way interaction between PTS symptoms and subjective sleep quality on cannabis use frequency. A significant three-way interaction (i.e., PTS Symptoms × Poor Subjective Sleep Quality × Assigned Sex) indicated the two-way interaction between PTS symptoms and sleep quality for both weekly drinks and cannabis use frequency was stronger among male compared to female participants. Study findings suggest sleep quality is an important factor contributing to the relation between PTS symptom severity and substance use among college students. Strategies for assessing and improving sleep quality and PTS symptoms can be incorporated into prevention and intervention efforts targeting substance use related harm for college students.

Stakeholder engagement to inform evidence-based treatment implementation for children's mental health: a scoping review.

BACKGROUND: There is a pervasive mental health treatment gap for children across the globe. Engaging stakeholders in child mental health evidence-based treatment (EBT) implementation projects may increase the likelihood of successful EBT implementation, thereby better addressing the treatment gap. However, little is known about the extent of stakeholder engagement to inform the implementation of child mental health EBTs. METHODS: We conducted a scoping review to characterize stakeholder engagement in child mental health EBT implementation projects, including what stakeholders are engaged, how they are engaged, when they are engaged, where they are engaged (i.e., location of projects), why they are engaged, and the reported impacts of stakeholder engagement. We searched seven databases: MEDLINE, PsycInfo, Embase, ERIC, CINAHL Complete, Scopus, and Web of Science Core Collection. To be included, studies had to report on some form of stakeholder engagement that was undertaken to inform or explain the implementation of a child mental health EBT. We performed data extraction and synthesis to describe key study and stakeholder characteristics, stakeholder engagement methods and rationales, reported impacts of stakeholder engagement, and quality of reporting on stakeholder engagement. RESULTS: In total, 122 manuscripts met our inclusion criteria, from which we identified a total of 103 unique child mental health EBT implementation projects. Projects spanned 22 countries, which included low-, lower-middle, upper-middle, and high-income countries. The largest number of projects was in the USA and conducted in public mental health settings. Most projects engaged EBT providers during the active implementation phase and with limited depth, often gathering information from stakeholders without sharing decision-making power in implementation efforts. Across projects, impacts of stakeholder engagement spanned all of Proctor and colleague's implementation outcomes. CONCLUSIONS: Given that stakeholder engagement is often shallow and with limited shared decision-making, additional effort should be made to increase engagement to preempt challenges to EBT implementation and ensure implementation success. Such efforts may ensure the just distribution of power in EBT implementation efforts. TRIAL REGISTRATION: All procedures were pre-registered on the Open Science Framework prior to conducting the literature search (DOI 10.17605/OSF.IO/GR9AP ).

A meta-analysis on the affect regulation function of real-time self-injurious thoughts and behaviours.

Prominent theories suggest that self-injurious thoughts and behaviours are negatively reinforced by decreased negative affect. The present meta-analysis quantifies effects from intensive longitudinal studies measuring negative affect and self-injurious thoughts and behaviours. We obtained data from 38 of the 79 studies (48%, 22 unique datasets) involving N = 1,644 participants (80% female, 75% white). Individual-participant data meta-analyses revealed changes in affect pre/post self-injurious thoughts and behaviours. In antecedent models, results supported increased negative affect before nonsuicidal self-injurious behaviour (k = 14, 95% CI 0.09 to 0.31) and suicidal thoughts (k = 14, 95% CI 0.03 to 0.19). For consequence models, negative affect was reduced following nonsuicidal self-injurious thoughts (k = 6, 95% CI -0.79 to -0.44), nonsuicidal self-injurious behaviours (k = 14, 95% CI -0.73 to -0.19) and suicidal thoughts (k = 13, 95% CI -0.79 to -0.23). Findings, which were not moderated by sampling strategies or sample composition, support the affect regulation function of self-injurious thoughts and behaviours.

Highly stretchable van der Waals thin films for adaptable and breathable electronic membranes.

The conformal integration of electronic systems with irregular, soft objects is essential for many emerging technologies. We report the design of van der Waals thin films consisting of staggered two-dimensional nanosheets with bond-free van der Waals interfaces. The films feature sliding and rotation degrees of freedom among the staggered nanosheets to ensure mechanical stretchability and malleability, as well as a percolating network of nanochannels to endow permeability and breathability. With an excellent mechanical match to soft biological tissues, the freestanding films can naturally adapt to local surface topographies and seamlessly merge with living organisms with highly conformal interfaces, rendering living organisms with electronic functions, including leaf-gate and skin-gate transistors. On-skin transistors allow high-fidelity monitoring and local amplification of skin potentials and electrophysiological signals.

Silver nanoparticles boost charge-extraction efficiency in Shewanella microbial fuel cells.

Microbial fuel cells (MFCs) can directly convert the chemical energy stored in organic matter to electricity and are of considerable interest for power generation and wastewater treatment. However, the current MFCs typically exhibit unsatisfactorily low power densities that are largely limited by the sluggish transmembrane and extracellular electron-transfer processes. Here, we report a rational strategy to boost the charge-extraction efficiency in Shewanella MFCs substantially by introducing transmembrane and outer-membrane silver nanoparticles. The resulting Shewanella-silver MFCs deliver a maximum current density of 3.85 milliamperes per square centimeter, power density of 0.66 milliwatts per square centimeter, and single-cell turnover frequency of 8.6 × 105 per second, which are all considerably higher than those of the best MFCs reported to date. Additionally, the hybrid MFCs feature an excellent fuel-utilization efficiency, with a coulombic efficiency of 81%.

Solution-processable 2D semiconductors for high-performance large-area electronics.

Two-dimensional (2D) materials, consisting of atomically thin crystal layers bound by the van der Waals force, have attracted much interest because of their potential in diverse technologies, including electronics, optoelectronics and catalysis1-10. In particular, solution-processable 2D semiconductor (such as MoS2) nanosheets are attractive building blocks for large-area thin-film electronics. In contrast to conventional zero- and one-dimensional nanostructures (quantum dots and nanowires, respectively), which are typically plagued by surface dangling bonds and associated trapping states, 2D nanosheets have dangling-bond-free surfaces. Thin films created by stacking multiple nanosheets have atomically clean van der Waals interfaces and thus promise excellent charge transport11-15. However, preparing high-quality solution-processable 2D semiconductor nanosheets remains a challenge. For example, MoS2 nanosheets and thin films produced using lithium intercalation and exfoliation are plagued by the presence of the metallic 1T phase and poor electrical performance (mobilities of about 0.3 square centimetres per volt per second and on/off ratios of less than 10)2,12, and materials produced by liquid exfoliation exhibit an intrinsically broad thickness distribution, which leads to poor film quality and unsatisfactory thin-film electrical performance (mobilities of about 0.4 square centimetres per volt per second and on/off ratios of about 100)14,16,17. Here we report a general approach to preparing highly uniform, solution-processable, phase-pure semiconducting nanosheets, which involves the electrochemical intercalation of quaternary ammonium molecules (such as tetraheptylammonium bromide) into 2D crystals, followed by a mild sonication and exfoliation process. By precisely controlling the intercalation chemistry, we obtained phase-pure, semiconducting 2H-MoS2 nanosheets with a narrow thickness distribution. These nanosheets were then further processed into high-performance thin-film transistors, with room-temperature mobilities of about 10 square centimetres per volt per second and on/off ratios of 106 that greatly exceed those obtained for previous solution-processed MoS2 thin-film transistors. The scalable fabrication of large-area arrays of thin-film transistors enabled the construction of functional logic gates and computational circuits, including an inverter, NAND, NOR, AND and XOR gates, and a logic half-adder. We also applied our approach to other 2D materials, including WSe2, Bi2Se3, NbSe2, In2Se3, Sb2Te3 and black phosphorus, demonstrating its potential for generating versatile solution-processable 2D materials.

The burden of diabetes mellitus for medicare beneficiaries.

The objective was to estimate health care costs and utilization for Medicare beneficiaries with type 1 (T1DM) or type 2 (T2DM) diabetes and their respective matched control cohorts. A retrospective claims cohort analysis was used to assess direct health care cost and utilization of health services in 2009 for patients aged 65-89 who were enrolled in a Medicare Advantage Plus prescription drug plan. Patients were matched 1:1 with patients without diabetes. All-cause health care costs for 2009 were calculated as the sum of all medical and pharmacy claims. The analysis included 6562 patients with T1DM and an equal number of matched controls, and 194,775 patients with T2DM and an equal number of matched controls. There were no significant demographic differences between cohorts for matched variables. Patients with T2DM had significantly higher mean Deyo/Charlson Comorbidity Index scores compared with their controls (2.47 versus 0.77; P<0.001), although all groups reported a high rate of costly comorbidities such as hypertension and heart disease. Mean all-cause health care costs per patient per year were significantly higher for patients with T1DM and T2DM versus controls for inpatient hospitalizations; outpatient, office, and emergency room visits; pharmacy expenditures; and total health care costs for 2009 (T1DM group: $20,701±$30,201; T1DM-matched control group: $6,537±$10,441; T2DM group: $10,437±$18,518; T2DM-matched control group: $6,505±$11,140). Diabetes escalates health care costs for Medicare Advantage Plus patients compared with patients in the same plan without diabetes, regardless of comorbidities.

A general approach to site-specific antibody drug conjugates.

Using an expanded genetic code, antibodies with site-specifically incorporated nonnative amino acids were produced in stable cell lines derived from a CHO cell line with titers over 1 g/L. Using anti-5T4 and anti-Her2 antibodies as model systems, site-specific antibody drug conjugates (NDCs) were produced, via oxime bond formation between ketones on the side chain of the incorporated nonnative amino acid and hydroxylamine functionalized monomethyl auristatin D with either protease-cleavable or noncleavable linkers. When noncleavable linkers were used, these conjugates were highly stable and displayed improved in vitro efficacy as well as in vivo efficacy and pharmacokinetic stability in rodent models relative to conventional antibody drug conjugates conjugated through either engineered surface-exposed or reduced interchain disulfide bond cysteine residues. The advantages of the oxime-bonded, site-specific NDCs were even more apparent when low-antigen-expressing (2+) target cell lines were used in the comparative studies. NDCs generated with protease-cleavable linkers demonstrated that the site of conjugation had a significant impact on the stability of these rationally designed prodrug linkers. In a single-dose rat toxicology study, a site-specific anti-Her2 NDC was well tolerated at dose levels up to 90 mg/kg. These experiments support the notion that chemically defined antibody conjugates can be synthesized in commercially relevant yields and can lead to antibody drug conjugates with improved properties relative to the heterogeneous conjugates formed by nonspecific chemical modification.

Site-specific antibody-polymer conjugates for siRNA delivery.

We describe here the development of site-specific antibody-polymer conjugates (APCs) for the selective delivery of small interference RNAs (siRNAs) to target cells. APCs were synthesized in good yields by conjugating an aminooxy-derivatized cationic block copolymer to an anti-HER2 Fab or full-length IgG by means of genetically encoded p-acetyl phenylalanine (pAcF). The APCs all showed binding affinity comparable to that of HER2 as their native counterparts and no significant cellular cytotoxicity. Mutant S202-pAcF Fab and Q389-pAcF IgG polymer conjugates specifically delivered siRNAs to HER2(+) cells and mediated potent gene silencing at both the mRNA and protein levels. However, a mutant A121-pAcF IgG polymer conjugate, despite its high binding affinity to HER2 antigen, did not induce a significant RNA interference response in HER2(+) cells, presumably due to steric interference with antigen binding and internalization. These results highlight the importance of conjugation site on the activity of antibody-polymer-based therapeutics and suggest that such chemically defined APCs may afford a useful targeted delivery platform for siRNAs or other nucleic acid-based therapies.

Impact of exacerbations on health care cost and resource utilization in chronic obstructive pulmonary disease patients with chronic bronchitis from a predominantly Medicare population.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system. COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system. This study examined health care utilization and cost among these patients. METHODS: For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population. This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009. Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD. Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year. Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use. Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics. RESULTS: The final study sample involved 8554 patients; mean age was 70.1±8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation. COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations. All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations. Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs. CONCLUSIONS: The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs. New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease.

A statewide collaborative initiative to improve the quality of care for patients with acute myocardial infarction and heart failure.

BACKGROUND: To enhance quality improvement, we created a unique statewide collaboration among 3 organizations: the Virginia Health Quality Center (Virginia's Medicare Quality Improvement Organization), the American College of Cardiology, and the American Heart Association. The goal was to improve discharge measures for acute myocardial infarction and heart failure. METHODS AND RESULTS: In 2004, 29 hospitals participated in the collaborative initiative. Using Medicare data submitted from 2004 through the second quarter of 2006, we analyzed adherence to individual discharge measures and all-or-none appropriate care measures for acute myocardial infarction, heart failure, and both. To control for differences in hospital characteristics, we were able to match 21 of the participating hospitals with 21 similar nonparticipating hospitals. In this paired analysis, the total appropriate care measure increased from 61% to 77% in participating hospitals compared with an increase from 51% to 60% in nonparticipating hospitals (P<0.0001). A generalized linear mixed model examining the full data set at the patient level failed to show a clear advantage among participating hospitals. Participating hospitals had higher baseline rates for most quality measures, suggesting a possible effect of a prior collaborative. Further analysis of only hospitals that participated in a prior collaborative showed that participants in the current collaborative initiative had higher rates of improvement for 7 of 10 quality measures and appropriate care measures for heart failure, acute myocardial infarction, or both (all P<0.05). CONCLUSIONS: We report a unique collaboration of a Medicare Quality Improvement Organization and 2 national organizations to address quality of care for acute myocardial infarction and heart failure. A composite measure of quality (the total appropriate care measure) improved more in the participating hospitals during the timeframe of the intervention, although the greater improvement in this and other measures in the participating hospitals appeared to be dependent on participation in a prior collaborative initiative.

Improvement in oncology practice performance through voluntary participation in the Quality Oncology Practice Initiative.

PURPOSE: The Quality Oncology Practice Initiative (QOPI) became available to all American Society of Clinical Oncology member physicians in 2006 as a voluntary medical oncology practice-based quality measurement and improvement project. QOPI assesses practice performance for a series of evidence- and consensus-based process measures, relying on practices to complete structured chart reviews and submit data via a secure Web-based portal. METHODS: This analysis focused on the 71 practices that participated in both the March and September 2006 data collections (7,624 charts abstracted in March and 10,240 in September). Among 33 measures common to both collections, five measures were closely correlated, and 28 are included in the final analysis. Composite scores were created for six different domains of care. Statistical significance was tested on both absolute changes and relative changes (relative failure reduction) of quality measures from baseline to follow-up and between the lower quartile and all other quartiles. RESULTS: Practice performance on individual measures varied between 18.8% and 98.6%. Mean overall performance as measured by a composite score increased from 78.7% in March to 82.3% in September (P < .05). Improvement was most marked among practices originally performing in the bottom quartile. Using a composite score, the absolute and relative performance for the bottom quartile improved by 27% and 35%, respectively, statistically superior to that of all others. CONCLUSION: Practices that participated in QOPI demonstrated improved performance in self-reported process measures, with the greatest improvement demonstrated in initially low-performing practices.