Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts.

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.

General resilience: Conceptual formulation and quantitative assessment for intervention development in the urban wastewater system.

General resilience addresses the resilience of a water system to any threat including unknowns, in contrast to specified resilience to individual identified threats. However, quantification of general resilience is challenging and previous assessments have typically been qualitative or based on system properties that are assumed to be indicative of resilient performance. Here we present a General Resilience Assessment Methodology (GRAM), which uses a middle-state based approach to decompose general resilience into contributing components to provide a quantitative and performance-based resilience assessment. GRAM enables the accounting of the effects of any threat if all modes of system failure are identifiable. It is applied to an integrated urban wastewater system where five interventions are explored. The results obtained show that whilst substantial improvements in specified resilience are achieved, increasing the general resilience of the system is challenging. However, general resilience analysis enables identification of system failure modes to which level of service is least resilient and highlights key opportunities for intervention development. GRAM is beneficial as it can inform the development of interventions to increase the resilience of a system to unknowns such as unforeseeable natural hazards in a quantifiable manner.

The EPIPHA-KNEE trial: Explaining Pain to target unhelpful pain beliefs to Increase PHysical Activity in KNEE osteoarthritis - a protocol for a multicentre, randomised controlled trial with clinical- and cost-effectiveness analysis.

BACKGROUND: Despite well-established benefits of physical activity for knee osteoarthritis (OA), nine of ten people with knee OA are inactive. People with knee OA who are inactive often believe that physical activity is dangerous, fearing that it will further damage their joint(s). Such unhelpful beliefs can negatively influence physical activity levels. We aim to evaluate the clinical- and cost-effectiveness of integrating physiotherapist-delivered pain science education (PSE), an evidence-based conceptual change intervention targeting unhelpful pain beliefs by increasing pain knowledge, with an individualised walking, strengthening, and general education program. METHODS: Two-arm, parallel-design, multicentre randomised controlled trial involving 198 people aged ≥50 years with painful knee OA who do not meet physical activity guideline recommendations or walk regularly for exercise. Both groups receive an individualised physiotherapist-led walking, strengthening, and OA/activity education program via 4x weekly in-person treatment sessions, followed by 4 weeks of at-home activities (weekly check-in via telehealth), with follow-up sessions at 3 months (telehealth) and 5 and 9 months (in-person). The EPIPHA-KNEE group also receives contemporary PSE about OA/pain and activity, embedded into all aspects of the intervention. Outcomes are assessed at baseline, 12 weeks, 6 and 12 months. Primary outcomes are physical activity level (step count; wrist-based accelerometry) and self-reported knee symptoms (WOMAC Total score) at 12 months. Secondary outcomes are quality of life, pain intensity, global rating of change, self-efficacy, pain catastrophising, depression, anxiety, stress, fear of movement, knee awareness, OA/activity conceptualisation, and self-regulated learning ability. Additional measures include adherence, adverse events, blinding success, COVID-19 impact on activity, intention to exercise, treatment expectancy/perceived credibility, implicit movement/environmental bias, implicit motor imagery, two-point discrimination, and pain sensitivity to activity. Cost-utility analysis of the EPIPHA-KNEE intervention will be undertaken, in addition to evaluation of cost-effectiveness in the context of primary trial outcomes. DISCUSSION: We will determine whether the integration of PSE into an individualised OA education, walking, and strengthening program is more effective than receiving the individualised program alone. Findings will inform the development and implementation of future delivery of PSE as part of best practice for people with knee OA. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12620001041943 (13/10/2020).

IGEMS: The Consortium on Interplay of Genes and Environment Across Multiple Studies - An Update.

The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene-environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14-103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with diverse outcomes, including mortality, physical functioning and psychological functioning; and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.

Impact hotspots of reduced nutrient discharge shift across the globe with population and dietary changes.

Reducing nutrient discharge from wastewater is essential to mitigating aquatic eutrophication; however, energy- and chemicals-intensive nutrient removal processes, accompanied with the emissions of airborne contaminants, can create other, unexpected, environmental consequences. Implementing mitigation strategies requires a complete understanding of the effects of nutrient control practices, given spatial and temporal variations. Here we simulate the environmental impacts of reducing nutrient discharge from domestic wastewater in 173 countries during 1990-2050. We find that improvements in wastewater infrastructure achieve a large-scale decline in nutrient input to surface waters, but this is causing detrimental effects on the atmosphere and the broader environment. Population size and dietary protein intake have the most significant effects over all the impacts arising from reduction of wastewater nutrients. Wastewater-related impact hotspots are also shifting from Asia to Africa, suggesting a need for interventions in such countries, mostly with growing populations, rising dietary intake, rapid urbanisation, and inadequate sanitation.

Cost-Effective River Water Quality Management using Integrated Real-Time Control Technology.

Integrated real-time control (RTC) of urban wastewater systems is increasingly presented as a promising and emerging strategy to deliver improved surface water quality by responsive operation according to real-time data collected from the sewer system, treatment plant, and the receiving water. However, the detailed benefits and costs associated with integrated RTC have yet to be comprehensively evaluated. Built on state-of-the-art modeling and analytical tools, a three-step framework is proposed to develop integrated RTC strategies which cost-effectively maximize environmental outcomes. Results from a case study show integrated RTC can improve river quality by over 20% to meet the "good status" requirements of the EU Water Framework Directive with a 15% reduced cost, due to responsive aeration with changing environmental assimilation capacity. The cost-effectiveness of integrated RTC strategies is further demonstrated against tightening environmental standards (to the strictest levels) and against two commonly used compliance strategies. Compared to current practices (seasonal/monthly based operation), integrated RTC strategies can reduce costs while improving resilience of the system to disturbances and reducing environmental risk.

Energy use and carbon footprints differ dramatically for diverse wastewater-derived carbonaceous substrates: An integrated exploration of biokinetics and life-cycle assessment.

Energy neutrality and reduction of carbon emissions are significant challenges to the enhanced sustainability of wastewater treatment plants (WWTPs). Harvesting energy from wastewater carbonaceous substrates can offset energy demands and enable net power generation; yet, there is limited research about how carbonaceous substrates influence energy and carbon implications of WWTPs with integrated energy recovery at systems-level. Consequently, this research uses biokinetics modelling and life cycle assessment philology to explore this notion, by tracing and assessing the quantitative flows of energy embodied or captured, and by exploring the carbon footprint throughout an energy-intensive activated sludge process with integrated energy recovery facilities. The results indicate that energy use and carbon footprint per cubic meter of wastewater treated, varies markedly with the carbon substrate. Compared with systems driven with proteins, carbohydrates or other short-chain fatty acids, systems fed with acetic acid realized energy neutrality with maximal net gain of power from methane combustion (0.198 kWh) and incineration of residual biosolids (0.153 kWh); and also achieved a negative carbon footprint (72.6 g CO2). The findings from this work help us to better understand and develop new technical schemes for improving the energy efficiency of WWTPs by repurposing the stream of carbon substrates across systems.

An Integrated Environmental Assessment of Green and Gray Infrastructure Strategies for Robust Decision Making.

The robustness of a range of watershed-scale "green" and "gray" drainage strategies in the future is explored through comprehensive modeling of a fully integrated urban wastewater system case. Four socio-economic future scenarios, defined by parameters affecting the environmental performance of the system, are proposed to account for the uncertain variability of conditions in the year 2050. A regret-based approach is applied to assess the relative performance of strategies in multiple impact categories (environmental, economic, and social) as well as to evaluate their robustness across future scenarios. The concept of regret proves useful in identifying performance trade-offs and recognizing states of the world most critical to decisions. The study highlights the robustness of green strategies (particularly rain gardens, resulting in half the regret of most options) over end-of-pipe gray alternatives (surface water separation or sewer and storage rehabilitation), which may be costly (on average, 25% of the total regret of these options) and tend to focus on sewer flooding and CSO alleviation while compromising on downstream system performance (this accounts for around 50% of their total regret). Trade-offs and scenario regrets observed in the analysis suggest that the combination of green and gray strategies may still offer further potential for robustness.

Does telephone care management help Medicaid beneficiaries with depression?

OBJECTIVES: While telephone care management has shown promise as a cost-effective approach to manage patients with depression, there is little evidence on the effectiveness of this method for Medicaid beneficiaries in managed care. This study examines a 1-year telephone care management intervention designed to help this low-income, hard-to-reach population enter and remain engaged with treatment. STUDY DESIGN: A randomized controlled trial of 499 Rhode Island Medicaid managed care beneficiaries with depression (all parents, average age of 35, and 90% women). Care managers conducted telephonic outreach with the intervention group to establish a relationship, initiate treatment, make referrals for in-person psychotherapy and/or medication treatment, and monitor treatment progress. The control group received usual care and was given a referral list of providers participating in the Medicaid program. METHODS: Primary outcomes were the use of health services and depression severity at 6 and 18 months. Administrative claims provided information on medical and mental health services use. Surveys of sample members provided information on depression severity. Analysis controlling for sociodemographic characteristics was done to assess the effectiveness of providing care management. RESULTS: Care managers contacted 91% of those assigned to the intervention group. The intervention was effective in enrolling participants into mental health services (42% in intervention group vs 31% in control; P = .05), but did not successfully reduce average depression severity. CONCLUSIONS: The intervention's lack of success in reducing depression severity for Medicaid beneficiaries suggests the need for more intensive interventions that strengthen telephone care management and potentially include in-person components as well.

Tissue engineering and developmental biology: going biomimetic.

This article contains the collective views expressed at the first session of the workshop "Tissue Engineering--The Next Generation," which was devoted to the interactions between developmental biology and tissue engineering. Donald Ingber discussed the chasms between developmental biology and tissue engineering from the perspective of a cell biologist who has had interest in tissue engineering since its early days. Van C. Mow shared a historical perspective on the development of tissue engineering as one of the first engineers involved in the field. David Butler offered an assessment of functional tissue engineering, a new area he helped establish and promote. Laura Niklason discussed how to be more effective in developing cellular therapies for large numbers of patients. Johnny Huard described his approach to tissue engineering, based on the use of muscle-derived cells. Jeremy Mao focused on cell homing and cell density in the context of native development and relevance to tissue engineering. Ioannis Yannas proposed a set of "rules" in organ regeneration. Collectively, the faculty expressed a remarkable level of enthusiasm for bridging the gaps between developmental biology and tissue engineering and offered new ideas on how to facilitate the interaction between the two fields.