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Differential susceptibility theory (DST) posits that individuals differ in their developmental plasticity: some children are highly responsive to both environmental adversity and support, while others are less affected. According to this theory, “plasticity” genes that confer risk for psychopathology in adverse environments may promote superior functioning in supportive environments. We tested DST using a broad measure of child genetic liability (based on birth parent psychopathology), adoptive home environmental variables (e.g., marital warmth, parenting stress, and internalizing symptoms), and measures of child externalizing problems (n = 337) and social competence (n = 330) in 54-month-old adopted children from the Early Growth and Development Study. This adoption design is useful for examining DST because children are placed at birth or shortly thereafter with nongenetically related adoptive parents, naturally disentangling heritable and postnatal environmental effects. We conducted a series of multivariable regression analyses that included Gene × Environment interaction terms and found little evidence of DST; rather, interactions varied depending on the environmental factor of interest, in both significance and shape. Our mixed findings suggest further investigation of DST is warranted before tailoring screening and intervention recommendations to children based on their genetic liability or “sensitivity.”
Quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) are commonly used in cost-effectiveness analysis (CEA) to measure health benefits. We sought to quantify and explain differences between QALY- and DALY-based cost-effectiveness ratios, and explore whether using one versus the other would materially affect conclusions about an intervention's cost-effectiveness.
We identified CEAs using both QALYs and DALYs from the Tufts Medical Center CEA Registry and Global Health CEA Registry, with a supplemental search to ensure comprehensive literature coverage. We calculated absolute and relative differences between the QALY- and DALY-based ratios, and compared ratios to common benchmarks (e.g., 1× gross domestic product per capita). We converted reported costs into US dollars.
Among eleven published CEAs reporting both QALYs and DALYs, seven focused on pharmaceuticals and infectious disease, and five were conducted in high-income countries. Four studies concluded that the intervention was “dominant” (cost-saving). Among the QALY- and DALY-based ratios reported from the remaining seven studies, absolute differences ranged from approximately $2 to $15,000 per unit of benefit, and relative differences from 6–120 percent, but most differences were modest in comparison with the ratio value itself. The values assigned to utility and disability weights explained most observed differences. In comparison with cost-effectiveness thresholds, conclusions were consistent regardless of the ratio type in ten of eleven cases.
Our results suggest that although QALY- and DALY-based ratios for the same intervention can differ, differences tend to be modest and do not materially affect comparisons to common cost-effectiveness thresholds.
The transmission rate of methicillin-resistant Staphylococcus aureus (MRSA) to gloves or gowns of healthcare personnel (HCP) caring for MRSA patients in a non–intensive care unit setting was 5.4%. Contamination rates were higher among HCP performing direct patient care and when patients had detectable MRSA on their body. These findings may inform risk-based contact precautions.
We demonstrate an application evaluating carbon sequestration benefits from federal policy alternatives. Using detailed forest inventory data, we projected carbon sequestration outcomes in the coterminous 48 states for a baseline scenario and three policy scenarios through 2050. Alternatives included (1) reducing deforestation from development, (2) afforestation in the eastern United States and reforestation in the western United States, and (3) reducing stand-replacing wildfires. We used social cost of carbon estimates to evaluate the present value of carbon sequestration benefits gained with each policy. Results suggest that afforestation and reforestation would provide the greatest marginal increase in carbon benefit, far exceeding policy cost.
The Early Growth and Development Study (EGDS) is a prospective adoption study of birth parents, adoptive parents and adopted children (n = 561 adoptees). The original sample has been expanded to include siblings of the EGDS adoptees who were reared by the birth mother and assessed beginning at age 7 years (n = 217 biological children), and additional siblings in both the birth and adoptive family homes, recruited when the adoptees were 8–15 years old (n = 823). The overall study aims are to examine how family, peer and contextual processes affect child and adolescent adjustment, and to examine their interplay (mediation, moderation) with genetic influences. Adoptive and birth parents were originally recruited through adoption agencies located throughout the USA following the birth of a child. Assessments are ongoing and occurred in 9 month’s intervals until the adoptees turned 3 years of age, and in 1 to 2 year intervals thereafter through age 15. Data collection includes the following primary constructs: child temperament, behavior problems, mental health, peer relations, executive functioning, school performance and health; birth and adoptive parent personality characteristics, mental health, health, context, substance use, parenting and marital relations; and the prenatal environment. Findings highlight the power of the adoption design to detect environmental influences on child development and provide evidence of complex interactions and correlations between genetic, prenatal environmental and postnatal environmental influences on a range of child outcomes. The study sample, procedures and an overview of findings are summarized and ongoing assessment activities are described.
To advance research from Dishion and others on associations between parenting and peer problems across childhood, we used a sample of 177 sibling pairs reared apart since birth (because of adoption of one of the siblings) to examine associations between parental hostility and children's peer problems when children were ages 7 and 9.5 years (n = 329 children). We extended conventional cross-lagged parent–peer models by incorporating child inhibitory control as an additional predictor and examining genetic contributions via birth mother psychopathology. Path models indicated a cross-lagged association from parental hostility to later peer problems. When child inhibitory control was included, birth mother internalizing symptoms were associated with poorer child inhibitory control, which was associated with more parental hostility and peer problems. The cross-lagged paths from parental hostility to peer problems were no longer significant in the full model. Multigroup analyses revealed that the path from birth mother internalizing symptoms to child inhibitory control was significantly higher for birth parent–reared children, indicating the possible contribution of passive gene–environment correlation to this association. Exploratory analyses suggested that each child's unique rearing context contributed to his or her inhibitory control and peer behavior. Implications for the development of evidence-based interventions are discussed.
We used a survey to characterize contemporary infection prevention and antibiotic stewardship program practices across 64 healthcare facilities, and we compared these findings to those of a similar 2013 survey. Notable findings include decreased frequency of active surveillance for methicillin-resistant Staphylococcus aureus, frequent active surveillance for carbapenem-resistant Enterobacteriaceae, and increased support for antibiotic stewardship programs.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
To enhance enrollment into randomized clinical trials (RCTs), we proposed electronic health record-based clinical decision support for patient–clinician shared decision-making about care and RCT enrollment, based on “mathematical equipoise.”
As an example, we created the Knee Osteoarthritis Mathematical Equipoise Tool (KOMET) to determine the presence of patient-specific equipoise between treatments for the choice between total knee replacement (TKR) and nonsurgical treatment of advanced knee osteoarthritis.
With input from patients and clinicians about important pain and physical function treatment outcomes, we created a database from non-RCT sources of knee osteoarthritis outcomes. We then developed multivariable linear regression models that predict 1-year individual-patient knee pain and physical function outcomes for TKR and for nonsurgical treatment. These predictions allowed detecting mathematical equipoise between these two options for patients eligible for TKR. Decision support software was developed to graphically illustrate, for a given patient, the degree of overlap of pain and functional outcomes between the treatments and was pilot tested for usability, responsiveness, and as support for shared decision-making.
The KOMET predictive regression model for knee pain had four patient-specific variables, and an r2 value of 0.32, and the model for physical functioning included six patient-specific variables, and an r2 of 0.34. These models were incorporated into prototype KOMET decision support software and pilot tested in clinics, and were generally well received.
Use of predictive models and mathematical equipoise may help discern patient-specific equipoise to support shared decision-making for selecting between alternative treatments and considering enrollment into an RCT.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
The Richtmyer–Meshkov instability (RMI) is experimentally investigated in a vertical shock tube using a broadband initial condition imposed on an interface between a helium–acetone mixture and argon (Atwood number
). In the present work, a shear layer is introduced at the interface to serve as a statistically repeatable, broadband initial condition to the RMI, and the density interface is accelerated by either an
planar shock wave. The development of the ensuing mixing layer is investigated using simultaneous planar laser-induced fluorescence (PLIF) and particle image velocimetry (PIV). PLIF images are processed to reveal the light-gas mole fraction, while PIV particle image pairs yield corresponding two-component planar velocity results. Field structure and distribution are explored through probability density functions (PDFs), and a decomposition is performed on concentration and velocity results to obtain a mean flow field and define fluctuations. Simultaneous concentration and velocity field measurements allow – for the first time in this regime – experimentally determined turbulence quantities such as Reynolds stresses, turbulent mass-flux velocities and turbulent kinetic energy to be obtained. We show that by the latest times the mixing layer has passed the turbulent threshold, and there is evidence of turbulent mixing occurring sooner for the higher Mach number case. Interface measurements show nonlinear growth with a power-law fit to the thickness data, and that integral measurements of mixing layer thickness are proportional to threshold measurements. Spectral analysis demonstrates the emergence of an inertial range with a slope
when considering both density and velocity effects in planar turbulent kinetic energy (TKE) measurements.
Herbicide resistance, and in particular multiple-herbicide resistance, poses an ever-increasing threat to food security. A biotype of junglerice [Echinochloa colona (L.) Link] with resistance to four herbicides, imazamox, fenoxaprop-P-ethyl, quinclorac, and propanil, each representing a different mechanism of action, was identified in Sunflower County, MS. Dose responses were performed on the resistant biotype and a biotype sensitive to all four herbicides to determine the level of resistance. Application of a cytochrome P450 inhibitor, malathion, with the herbicides imazamox and quinclorac resulted in increased susceptibility in the resistant biotype. Differential gene expression analysis of resistant and sensitive plants revealed that 170 transcripts were upregulated in resistant plants relative to sensitive plants and 160 transcripts were upregulated in sensitive plants. In addition, 507 transcripts were only expressed in resistant plants and 562 only in sensitive plants. A subset of these transcripts were investigated further using quantitative PCR (qPCR) to compare gene expression in resistant plants with expression in additional sensitive biotypes. The qPCR analysis identified two transcripts, a kinase and a glutathione S-transferase that were significantly upregulated in resistant plants compared with the sensitive plants. A third transcript, encoding an F-box protein, was downregulated in the resistant plants relative to the sensitive plants. As no cytochrome P450s were differentially expressed between the resistant and sensitive plants, a single-nucleotide polymorphism analysis was performed, revealing several nonsynonymous point mutations of interest. These candidate genes will require further study to elucidate the resistance mechanisms present in the resistant biotype.
To summarize ways that networks of community-based organizations (CBO), in partnership with public health departments, contribute to community recovery from disaster.
The study was conducted using an online survey administered one and 2 years after Hurricane Sandy to the partnership networks of 369 CBO and the New York Department of Health and Mental Hygiene. The survey assessed the structure and durability of networks, how they were influenced by storm damage, and whether more connected networks were associated with better recovery outcomes.
During response and recovery, CBOs provide an array of critical public health services often outside their usual scope. New CBO partnerships were formed to support recovery, particularly in severely impacted areas. CBOs that were more connected to other CBOs and were part of a long-term recovery committee reported greater impacts on the community; however, a partnership with the local health department was not associated with recovery impacts.
CBO partners are flexible in their scope of services, and CBO partnerships often emerge in areas with the greatest storm damage, and subsequently the greatest community needs. National policies will advance if they account for the dynamic and emergent nature of these partnerships and their contributions, and clarify the role of government partners. (Disaster Med Public Health Preparedness. 2018;12:635–643)
Maternal trauma is a complex risk factor that has been linked to adverse child outcomes, yet the mechanisms underlying this association are not well understood. This study, which included adoptive and biological families, examined the heritable and environmental mechanisms by which maternal trauma and associated depressive symptoms are linked to child internalizing and externalizing behaviors. Path analyses were used to analyze data from 541 adoptive mother–adopted child (AM–AC) dyads and 126 biological mother–biological child (BM–BC) dyads; the two family types were linked through the same biological mother. Rearing mother's trauma was associated with child internalizing and externalizing behaviors in AM–AC and BM–BC dyads, and this association was mediated by rearing mothers’ depressive symptoms, with the exception of biological child externalizing behavior, for which biological mother trauma had a direct influence only. Significant associations between maternal trauma and child behavior in dyads that share only environment (i.e., AM–AC dyads) suggest an environmental mechanism of influence for maternal trauma. Significant associations were also observed between maternal depressive symptoms and child internalizing and externalizing behavior in dyads that were only genetically related, with no shared environment (i.e., BM–AC dyads), suggesting a heritable pathway of influence via maternal depressive symptoms.
We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.
This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.
Genetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).
These data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.
To determine whether antimicrobial-impregnated textiles decrease the acquisition of pathogens by healthcare provider (HCP) clothing.
We completed a 3-arm randomized controlled trial to test the efficacy of 2 types of antimicrobial-impregnated clothing compared to standard HCP clothing. Cultures were obtained from each nurse participant, the healthcare environment, and patients during each shift. The primary outcome was the change in total contamination on nurse scrubs, measured as the sum of colony-forming units (CFU) of bacteria.
PARTICIPANTS AND SETTING
Nurses working in medical and surgical ICUs in a 936-bed tertiary-care hospital.
Nurse subjects wore standard cotton-polyester surgical scrubs (control), scrubs that contained a complex element compound with a silver-alloy embedded in its fibers (Scrub 1), or scrubs impregnated with an organosilane-based quaternary ammonium and a hydrophobic fluoroacrylate copolymer emulsion (Scrub 2). Nurse participants were blinded to scrub type and randomly participated in all 3 arms during 3 consecutive 12-hour shifts in the intensive care unit.
In total, 40 nurses were enrolled and completed 3 shifts. Analyses of 2,919 cultures from the environment and 2,185 from HCP clothing showed that scrub type was not associated with a change in HCP clothing contamination (P=.70). Mean difference estimates were 0.118 for the Scrub 1 arm (95% confidence interval [CI], −0.206 to 0.441; P=.48) and 0.009 for the Scrub 2 rm (95% CI, −0.323 to 0.342; P=.96) compared to the control. HCP became newly contaminated with important pathogens during 19 of the 120 shifts (16%).
Antimicrobial-impregnated scrubs were not effective at reducing HCP contamination. However, the environment is an important source of HCP clothing contamination.
We describe the design and performance of the Engineering Development Array, which is a low-frequency radio telescope comprising 256 dual-polarisation dipole antennas working as a phased array. The Engineering Development Array was conceived of, developed, and deployed in just 18 months via re-use of Square Kilometre Array precursor technology and expertise, specifically from the Murchison Widefield Array radio telescope. Using drift scans and a model for the sky brightness temperature at low frequencies, we have derived the Engineering Development Array’s receiver temperature as a function of frequency. The Engineering Development Array is shown to be sky-noise limited over most of the frequency range measured between 60 and 240 MHz. By using the Engineering Development Array in interferometric mode with the Murchison Widefield Array, we used calibrated visibilities to measure the absolute sensitivity of the array. The measured array sensitivity matches very well with a model based on the array layout and measured receiver temperature. The results demonstrate the practicality and feasibility of using Murchison Widefield Array-style precursor technology for Square Kilometre Array-scale stations. The modular architecture of the Engineering Development Array allows upgrades to the array to be rolled out in a staged approach. Future improvements to the Engineering Development Array include replacing the second stage beamformer with a fully digital system, and to transition to using RF-over-fibre for the signal output from first stage beamformers.
Organic molecular crystals are often noncubic and contain significant steric hindrance within their structure to resist dislocation motion. Plastic deformation in these systems can be imparted during processing (tableting and comminution of powders), and the defect density impacts subsequent properties and performance. This study measured the elastic and plastic properties of representative monoclinic, orthorhombic, and triclinic molecular crystalline structures using nanoindentation of as-grown sub-mm single crystals. The variation in modulus due to in-plane rotational orientation, relative to a Berkovich tip, was approximately equal to the variation of a given crystal at a fixed orientation. The onset of plasticity occurs consistently at shear stresses between 1 and 5% of the elastic modulus in all three crystal systems, and the hardness to modulus ratio suggests conventional Berkovich tips do not generate fully self-similar plastic zones in these materials. This provides guidance for mechanical models of tableting, machining, and property assessment of molecular crystals.