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People with opioid use disorder (OUD) have substantially higher standardised mortality rates compared with the general population. However, lack of individualised prognostic information presents challenges in personalisation of addiction treatment delivery.
Aims
To develop and validate the first prognostic models to estimate 6-month all-cause and drug-related mortality risk for people diagnosed with OUD using indicators recorded at baseline assessment in addiction services in England.
Method
Thirteen candidate prognostic variables, including sociodemographic, injecting status and health and mental health factors, were identified from nationally linked addiction treatment, hospital admission and death records from 1 April 2013 to 1 April 2022. Multivariable Cox regression models were developed with a fractional polynomial approach for continuous variables, and missing data were addressed using multiple imputation by chained equations. Validation was undertaken using bootstrapping methods. Discrimination was assessed using Harrel’s C and D statistics alongside examination of observed-to-predicted event rates and calibration curve slopes.
Results
Data were available for 236 064 people with OUD, with 2427 deaths due to any cause, including 1289 due to drug-related causes. Both final models demonstrated good optimism-adjusted discrimination and calibration, with all-cause and drug-related models, respectively, demonstrating Harrell’s C statistics of 0.73 (95% CI 0.71–0.75) and 0.74 (95% CI 0.72–0.76), D-statistics of 1.01 (95% CI 0.95–1.08) and 1.07 (95% CI 0.98–1.16) and calibration slopes of 1.01 (95% CI 0.95–1.08) and 1.01 (95% CI 0.94–1.10).
Conclusions
We developed and internally validated Roberts’ OUD mortality risk, with the first models to accurately quantify individualised absolute 6-month mortality risks in people with OUD presenting to addiction services. Independent validation is warranted to ensure these models have the optimal utility to assist wider future policy, commissioning and clinical decision-making.
We conducted a pilot study of implementing community health workers (CHWs) to assist patients with hypertension and social needs. As part of clinical care, patients identified as having an unmet need were referred to a CHW. We evaluated changes in blood pressure and needs among 35 patients and conducted interviews to understand participants’ experiences. Participants had a mean age of 54.1 years and 29 were Black. Twenty-six completed follow-up. Blood pressure and social needs improved from baseline to 6 months. Participants reported being accepting of CHWs, but also challenges with establishing a relationship with a CHW and being unclear about their role.
Plausible values (PVs) are a standard multiple imputation tool for analysis of large education survey data, which measures latent proficiency variables. When latent proficiency is the dependent variable, we reconsider the standard institutionally generated PV methodology and find it applies with greater generality than shown previously. When latent proficiency is an independent variable, we show that the standard institutional PV methodology produces biased inference because the institutional conditioning model places restrictions on the form of the secondary analysts’ model. We offer an alternative approach that avoids these biases based on the mixed effects structural equations model of Schofield (Modeling measurement error when using cognitive test scores in social science research. Doctoral dissertation. Department of Statistics and Heinz College of Public Policy. Pittsburgh, PA: Carnegie Mellon University, 2008).
There are numerous adverse health outcomes associated with dementia caregiving, including increased stress and depression. Caregivers often face time-related, socioeconomic, geographic, and pandemic-related barriers to treatment. Thus, implementing mobile health (mHealth) interventions is one way of increasing caregivers’ access to supportive care. The objective of the current study was to collect data from a 3-month feasibility trial of a multicomponent mHealth intervention for dementia caregivers.
Participants and Methods:
40 community-dwelling dementia caregivers were randomized to receive the CARE-Well (Caregiver Assessment, Resources, and Education) App or internet links connected to caregiver education, support, and resources. Caregivers were encouraged to use the App or links at least 4 times per week for 3 months. The App consisted of self-assessments, caregiver and stress reduction education, behavior problem management, calendar reminders, and online social support. Caregivers completed measures of burden, depression, and desire to institutionalize at baseline and post-intervention. Feasibility data included App usage, retention and adherence rates, and treatment satisfaction. Data were analyzed via descriptive statistics.
Results:
Caregivers were mostly white (95%), female (68%), in their mid-60s, (M= 66.38, SD= 10.64), and well-educated (M= 15.52 years, SD= 2.26). Caregivers were mainly spouses (68%) or adult children (30%). Care recipients were diagnosed with mild (60%) or moderate (40%) dementia, with 80% diagnosed as having Alzheimer’s disease. Overall, the study had an 85% retention rate (80% for App group; 90% for links group). 58% of caregivers in the App group were considered high users, using the App >120 minutes over the course of 3 months (M= 362.42, SD= 432.68), and an average of 16.44 days (SD= 15.51). 15% of the sample was non-adherent due to time constraints, disinterest, and/or technology issues. Most participants (75%) using the App were mostly or very satisfied, about 87% would be likely or very likely to seek similar programs in the future, and 93% found the App mostly or very understandable. Groups did not significantly differ on clinical outcomes, although the study was not powered for an efficacy analysis. Within groups analysis revealed significant increases in depressive symptoms at post-treatment for caregivers in both groups.
Conclusions:
This study demonstrated initial feasibility of the CARE-Well App for dementia caregivers. App use was lower than expected, however, high satisfaction, ease of use, and willingness to use similar programs in the future were endorsed. Some caregivers did not complete the intervention due to caregiving responsibilities, general disinterest, and/or technology issues. Although the study was not designed to assess clinical outcomes, we found that both groups reported higher depressive symptoms at post-treatment. This finding was unexpected and might reflect pandemic-related stress, which has been shown to particularly impact dementia caregivers. Future studies should address the efficacy of multicomponent mHealth interventions for dementia caregivers and the effects of increased dose on clinical outcomes. mHealth interventions should be refined to cater to varying levels of technology literacy among caregivers, and further research should aim to better integrate interventions into caregivers’ routines to enhance treatment engagement.
Late-life depression (LLD) is characterized by differences in resting state functional connectivity within and between intrinsic functional networks. This study examined whether clinical improvement to antidepressant medications is associated with pre-randomization functional connectivity in intrinsic brain networks.
Methods
Participants were 95 elders aged 60 years or older with major depressive disorder. After clinical assessments and baseline MRI, participants were randomized to escitalopram or placebo with a two-to-one allocation for 8 weeks. Non-remitting participants subsequently entered an 8-week trial of open-label bupropion. The main clinical outcome was depression severity measured by MADRS. Resting state functional connectivity was measured between a priori key seeds in the default mode (DMN), cognitive control, and limbic networks.
Results
In primary analyses of blinded data, lower post-treatment MADRS score was associated with higher resting connectivity between: (a) posterior cingulate cortex (PCC) and left medial prefrontal cortex; (b) PCC and subgenual anterior cingulate cortex (ACC); (c) right medial PFC and subgenual ACC; (d) right orbitofrontal cortex and left hippocampus. Lower post-treatment MADRS was further associated with lower connectivity between: (e) the right orbitofrontal cortex and left amygdala; and (f) left dorsolateral PFC and left dorsal ACC. Secondary analyses associated mood improvement on escitalopram with anterior DMN hub connectivity. Exploratory analyses of the bupropion open-label trial associated improvement with subgenual ACC, frontal, and amygdala connectivity.
Conclusions
Response to antidepressants in LLD is related to connectivity in the DMN, cognitive control and limbic networks. Future work should focus on clinical markers of network connectivity informing prognosis.
Turning the wealth of health and social data into insights to promote better public health, while enabling more effective personalized care, is critically important for society. In particular, social determinants of health have a significant impact on individual health, well-being, and inequalities in health. However, concerns around accessing and processing such sensitive data, and linking different datasets, involve significant challenges, not least to demonstrate trustworthiness to all stakeholders. Emerging datatrust services provide an opportunity to address key barriers to health and social care data linkage schemes, specifically a loss of control experienced by data providers, including the difficulty to maintain a remote reidentification risk over time, and the challenge of establishing and maintaining a social license. Datatrust services are a sociotechnical evolution that advances databases and data management systems, and brings together stakeholder-sensitive data governance mechanisms with data services to create a trusted research environment. In this article, we explore the requirements for datatrust services, a proposed implementation—the Social Data Foundation, and an illustrative test case. Moving forward, such an approach would help incentivize, accelerate, and join up the sharing of regulated data, and the use of generated outputs safely amongst stakeholders, including healthcare providers, social care providers, researchers, public health authorities, and citizens.
The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
This chapter describes the current state of, and normative basis for, the law of reasonable royalties among the leading jurisdictions for patent infringement litigation, as well as the principal arguments for and against various practices relating to the calculation of reasonable royalties; and for each of the major issues discussed, the chapter provides one or more recommendations. The chapter’s principal recommendation is that, when applying a “bottom-up” approach to estimating reasonable royalties, courts should replace the Georgia-Pacific factors (and analogous factors used outside the United States) with a smaller list of considerations, specifically (1) calculating the incremental value of the invention and dividing it appropriately between the parties; (2) assessing market evidence, such as comparable licenses; and (3) where feasible and cost justified, using each of these first two considerations as a “check” on the accuracy of the other
Patent systems commonly empower courts to order accused or adjudged infringers to refrain from continuing infringing conduct in the future. Some patentees file suit for the primary purpose of obtaining and enforcing an injunction against infringement by a competitor, and even in cases in which the patentee is willing to license an invention to an accused infringer for an agreed price, the indirect monetary value of an injunction against future infringement can dwarf the amount a finder of fact is likely to award as compensation for past infringement. In some of these cases, an injunction, if granted, would impose costs on accused infringers or third parties that go well beyond the more intrinsic value of the patented technology. This chapter explores the theory behind injunctive relief in patent cases, surveys the availability of this remedy in major patent systems, and suggests a general framework for courts to use when deciding whether injunctive relief is appropriate in individual cases.
This paper discusses a pulse electroplating method for preparing copper (Cu)-coated gas diffusion electrodes (GDEs) for the electrochemical conversion of carbon dioxide (CO2) to hydrocarbons such as ethylene. Ionomer coating and air-plasma surface pre-treatments were explored as means of hydrophilizing the carbon surface to enable adhesion of electrodeposited material. The pulsed-current electrodeposition method used successfully generated copper and copper oxide micro- and nano-particles on the prepared surfaces. Copper(I) species identified on the ionomer-treated GDEs are presumed to be highly active for the selective generation of ethylene as compared to other gaseous byproducts of CO2 reduction. Conversely, copper catalysts deposited onto plasma-treated GDEs were found to have poor activity for hydrocarbon production, likely due to substantial metallic character. Of note, plasma treatment of an ionomer-treated GDE after copper plating yielded further improvements in catalytic activity and durability towards ethylene production.
On 1 December 2011 the West Antarctic Ice Sheet (WAIS) Divide ice-core project reached its final depth of 3405 m. The WAIS Divide ice core is not only the longest US ice core to date, but is also the highest-quality deep ice core, including ice from the brittle ice zone, that the US has ever recovered. The methods used at WAIS Divide to handle and log the drilled ice, the procedures used to safely retrograde the ice back to the US National Ice Core Laboratory (NICL) and the methods used to process and sample the ice at the NICL are described and discussed.
The tufa deposits of the Ghaap Plateau escarpment provide a rich, yet minimally explored, geological archive of climate and environmental history coincident with hominin evolution in South Africa. This study examines the sedimentary and geochemical records of ancient and modern tufas from Buxton-Norlim Limeworks, Groot Kloof, and Gorrokop, to assess the potential of these sediments for providing reliable chronologies of high-resolution, paleoenvironmental information. Chronometric dating demonstrates that tufa formation has occurred from at least the terminal Pliocene through to the modern day. The stable isotope records show a trend toward higher, more variable δ18O and δ13C values with decreasing age from the end of the Pliocene onwards. The long-term increase in δ18O values corresponds to increasingly arid conditions, while increasing δ13C values reflect the changing proportion of C3/C4 vegetation in the local environment. Analysis of the Thabaseek Tufa, in particular, provides valuable evidence for reconstructing the depositional and chronological context of the enigmatic Taung Child (Australopithecus africanus). Collectively, the results of the present study demonstrate the potential of these deposits for developing high-precision records of climate change and ultimately, for understanding the causal processes relating climate and hominin evolution.
Giant ragweed has been increasing as a major weed of row crops in the last30 yr, but quantitative data regarding its pattern and mechanisms of spreadin crop fields are lacking. To address this gap, we conducted a Web-basedsurvey of certified crop advisors in the U.S. Corn Belt and Ontario, Canada.Participants were asked questions regarding giant ragweed and cropproduction practices for the county of their choice. Responses were mappedand correlation analyses were conducted among the responses to determinefactors associated with giant ragweed populations. Respondents rated giantragweed as the most or one of the most difficult weeds to manage in 45% of421 U.S. counties responding, and 57% of responding counties reported giantragweed populations with herbicide resistance to acetolactate synthaseinhibitors, glyphosate, or both herbicides. Results suggest that giantragweed is increasing in crop fields outward from the east-central U.S. CornBelt in most directions. Crop production practices associated with giantragweed populations included minimum tillage, continuous soybean, andmultiple-application herbicide programs; ecological factors included giantragweed presence in noncrop edge habitats, early and prolonged emergence,and presence of the seed-burying common earthworm in crop fields. Managinggiant ragweed in noncrop areas could reduce giant ragweed migration fromnoncrop habitats into crop fields and slow its spread. Where giant ragweedis already established in crop fields, including a more diverse combinationof crop species, tillage practices, and herbicide sites of action will becritical to reduce populations, disrupt emergence patterns, and selectagainst herbicide-resistant giant ragweed genotypes. Incorporation of acereal grain into the crop rotation may help suppress early giant ragweedemergence and provide chemical or mechanical control options forlate-emerging giant ragweed.
This paper discusses a pulse electroplating method for developing tin (Sn)-decorated gas diffusion electrodes (GDEs) for the electrochemical conversion of carbon dioxide (CO2) to formate. The pulse-plated Sn electrodes achieved current densities up to 388 mA/cm2, more than two-fold greater than conventionally prepared electrodes (150 mA/cm2), both at a formate selectivity of 80%. Optical and microscopic analyses indicate improvements in deposition parameters could further enhance performance by reducing the catalyst particle size.
Objectives: Blast explosions are the most frequent mechanism of traumatic brain injury (TBI) in recent wars, but little is known about their long-term effects. Methods: Functional connectivity (FC) was measured in 17 veterans an average of 5.46 years after their most serious blast related TBI, and in 15 demographically similar veterans without TBI or blast exposure. Subcortical FC was measured in bilateral caudate, putamen, and globus pallidus. The default mode and fronto-parietal networks were also investigated. Results: In subcortical regions, between-groups t tests revealed altered FC from the right putamen and right globus pallidus. However, following analysis of covariance (ANCOVA) with age, depression (Center for Epidemiologic Studies Depression Scale), and posttraumatic stress disorder symptom (PTSD Checklist – Civilian version) measures, significant findings remained only for the right globus pallidus with anticorrelation in bilateral temporal occipital fusiform cortex, occipital fusiform gyrus, lingual gyrus, and cerebellum, as well as the right occipital pole. No group differences were found for the default mode network. Although reduced FC was found in the fronto-parietal network in the TBI group, between-group differences were nonsignificant after the ANCOVA. Conclusions: FC of the globus pallidus is altered years after exposure to blast related TBI. Future studies are necessary to explore the trajectory of changes in FC in subcortical regions after blast TBI, the effects of isolated versus repetitive blast-related TBI, and the relation to long-term outcomes in veterans. (JINS, 2016, 22, 631–642)
Having worked on several approaches to CO2 capture over the past decade, we have studied a great number of physical and chemical solvents as well as polymer and composite membranes. Initially, most of these materials were based upon ionic liquids (ILs), however due to challenges encountered in applying ILs to meet the demanding requirements in CO2 separation processes, there is a need to reconsider what role (if any) ILs might play in CO2 capture technologies. Ultimately, more promising and robust materials will not come from ILs themselves, but from retrosynthetic analysis and a reconsideration of which structural variables and properties are (and are not) important. The hybridization of the constituent parts into entirely new, yet seemingly familiar substances, can yield greatly improved properties and economics. This manuscript highlights recent work from our group based on lessons learned from ILs that have spurred the development of new amine solvents and polymer materials to better address the demanding process conditions and requirements of CO2 capture and related separations.
Dual-purpose winter wheat (fall-winter forage plus grain) production is an important economic enterprise in the southern Great Plains. Grazing termination to enable grain production is a critical decision. The objective is to determine the optimal grazing termination date for dual-purpose wheat. The value of knowing the occurrence of first hollow stem (FHS), a wheat growth threshold for grazing termination, is also determined. Results indicate that for most price situations grazing should be terminated at or before FHS. Marginal wheat returns from extended grazing were negative and the value of FHS information ranges from $1.50 to $10 per acre.