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Regular physical activity for adults is associated with optimal appetite regulation, though little work has been performed in adolescents. To address this gap in the literature, we conducted a study examining appetite across a range of physical activity and adiposity levels in adolescent males. Healthy males (n 46, 14–18 years old) were recruited across four body weight and activity categories: normal weight/high active (n 11), normal weight/low active (n 13), overweight, obese/high active (n 14), overweight and obese/low active (n 8). Participants from each group completed a 6-h appetite assessment session on Day 0, followed immediately by a 14-day free-living physical activity and dietary assessment period on Days 1–14, and a fitness test session occurring between Days 15–18. Subjective and objective assessment of appetite, resting energy expenditure, body composition using dual energy absorptiometry and thermic effect of feeding (TEF) was conducted on Day 0. Physiological variables in the normal weight low active group that were different than their peers included lower fat-free mass, cardiorespiratory fitness, glucose/fullness response to a standardised meal, TEF in response to a standardised meal, lower self-rated fullness and satiety and higher self-rated hunger to a standardised meal. Conversely, the overweight, obese high active group displayed better subjective appetite responses, but higher insulin responses to a standardised meal. Taken together, these results suggest that physical inactivity during adolescence has a negative impact on metabolic health and appetite control, which may contribute to future weight gain.
Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.
Methods
We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.
Results
We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).
Conclusions
Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.
Recent changes in US government priorities have serious negative implications for science that will compromise the integrity of mental health research, which focuses on vulnerable populations. Therefore, as editors of mental science journals and custodians of the academic record, we confirm with conviction our collective commitment to communicating the truth.
Web-based dietary interventions could support healthy eating. The Advice, Ideas and Motivation for My Eating (Aim4Me) trial investigated the impact of three levels of personalised web-based dietary feedback on diet quality in young adults. Secondary aims were to investigate participant retention, engagement and satisfaction.
Design:
Randomised controlled trial.
Setting:
Web-based intervention for young adults living in Australia.
Participants:
18–24-year-olds recruited across Australia were randomised to Group 1 (control: brief diet quality feedback), Group 2 (comprehensive feedback on nutritional adequacy + website nutrition resources) or Group 3 (30-min dietitian consultation + Group 2 elements). Australian Recommended Food Score (ARFS) was the primary outcome. The ARFS subscales and percentage energy from nutrient-rich foods (secondary outcomes) were analysed at 3, 6 and 12 months using generalised linear mixed models. Engagement was measured with usage statistics and satisfaction with a process evaluation questionnaire.
Results:
Participants (n 1005, 85 % female, mean age 21·7 ± 2·0 years) were randomised to Group 1 (n 343), Group 2 (n 325) and Group 3 (n 337). Overall, 32 (3 %), 88 (9 %) and 141 (14 %) participants were retained at 3, 6 and 12 months, respectively. Only fifty-two participants (15 % of Group 3) completed the dietitian consultation. No significant group-by-time interactions were observed (P > 0·05). The proportion of participants who visited the thirteen website pages ranged from 0·6 % to 75 %. Half (Group 2 = 53 %, Group 3 = 52 %) of participants who completed the process evaluation (Group 2, n 111; Group 3, n 90) were satisfied with the programme.
Conclusion:
Recruiting and retaining young adults in web-based dietary interventions are challenging. Future research should consider ways to optimise these interventions, including co-design methods.
The causal impacts of recreational cannabis legalization are not well understood due to the number of potential confounds. We sought to quantify possible causal effects of recreational cannabis legalization on substance use, substance use disorder, and psychosocial functioning, and whether vulnerable individuals are more susceptible to the effects of cannabis legalization than others.
Methods
We used a longitudinal, co-twin control design in 4043 twins (N = 240 pairs discordant on residence), first assessed in adolescence and now age 24–49, currently residing in states with different cannabis policies (40% resided in a recreationally legal state). We tested the effect of legalization on outcomes of interest and whether legalization interacts with established vulnerability factors (age, sex, or externalizing psychopathology).
Results
In the co-twin control design accounting for earlier cannabis frequency and alcohol use disorder (AUD) symptoms respectively, the twin living in a recreational state used cannabis on average more often (βw = 0.11, p = 1.3 × 10−3), and had fewer AUD symptoms (βw = −0.11, p = 6.7 × 10−3) than their co-twin living in an non-recreational state. Cannabis legalization was associated with no other adverse outcome in the co-twin design, including cannabis use disorder. No risk factor significantly interacted with legalization status to predict any outcome.
Conclusions
Recreational legalization was associated with increased cannabis use and decreased AUD symptoms but was not associated with other maladaptations. These effects were maintained within twin pairs discordant for residence. Moreover, vulnerabilities to cannabis use were not exacerbated by the legal cannabis environment. Future research may investigate causal links between cannabis consumption and outcomes.
‘Sea salt is made by boiling and evaporating sea water over the fire. Bay salt, by evaporating sea water, in pits clayed on the inside, by the heat of the sun. Basket salt is made by boiling away the water of salt springs over the fire. Rock salt is dug out of the ground’, wrote Charlotte Mason in The Lady's Assistant (1775), one of the most comprehensive eighteenth-century cookbooks. Although there were at least four variations of salt before the pre-industrial era, several historical recipes specified the use of bay salt (solar salt) for meat preservation, elevating its cultural status and implying that early modern actors had a refined understanding of salts, their tastes and their applications. This study uses scientific analysis to determine whether there is a biological or chemical basis for the superior reputation of bay salt for curing. Laboratory data suggest that bay salt contains microbes that produce nitrate and nitrite, which give the meat a more favourable taste and pleasant aesthetic. The authors thus demonstrate that combining insights from experimental archaeology with textual analysis of historical sources gives us a deeper understanding of historical uses of taste as an epistemic tool.
To describe the genomic analysis and epidemiologic response related to a slow and prolonged methicillin-resistant Staphylococcus aureus (MRSA) outbreak.
Design:
Prospective observational study.
Setting:
Neonatal intensive care unit (NICU).
Methods:
We conducted an epidemiologic investigation of a NICU MRSA outbreak involving serial baby and staff screening to identify opportunities for decolonization. Whole-genome sequencing was performed on MRSA isolates.
Results:
A NICU with excellent hand hygiene compliance and longstanding minimal healthcare-associated infections experienced an MRSA outbreak involving 15 babies and 6 healthcare personnel (HCP). In total, 12 cases occurred slowly over a 1-year period (mean, 30.7 days apart) followed by 3 additional cases 7 months later. Multiple progressive infection prevention interventions were implemented, including contact precautions and cohorting of MRSA-positive babies, hand hygiene observers, enhanced environmental cleaning, screening of babies and staff, and decolonization of carriers. Only decolonization of HCP found to be persistent carriers of MRSA was successful in stopping transmission and ending the outbreak. Genomic analyses identified bidirectional transmission between babies and HCP during the outbreak.
Conclusions:
In comparison to fast outbreaks, outbreaks that are “slow and sustained” may be more common to units with strong existing infection prevention practices such that a series of breaches have to align to result in a case. We identified a slow outbreak that persisted among staff and babies and was only stopped by identifying and decolonizing persistent MRSA carriage among staff. A repeated decolonization regimen was successful in allowing previously persistent carriers to safely continue work duties.
Substance use and psychiatric illness, particularly psychotic disorders, contribute to violence in emergency healthcare settings. However, there is limited research regarding the relationship between specific substances, psychotic symptoms and violent behaviour in such settings. We investigated the interaction between recent cannabinoid and stimulant use, and acute psychotic symptoms, in relation to violent behaviour in a British emergency healthcare setting.
Methods
We used electronic medical records from detentions of 1089 individuals under Section 136 of the UK Mental Health Act (1983 amended 2007), an emergency police power used to detain people for 24–36 h for psychiatric assessment. The relationship between recent cannabinoids and/or stimulant use, psychotic symptoms, and violent behaviour, was estimated using logistic regression.
Findings
There was evidence of recent alcohol or drug use in 64.5% of detentions. Violent incidents occurred in 12.6% of detentions. Psychotic symptoms increased the odds of violence by 4.0 [95% confidence intervals (CI) 2.2–7.4; p < 0.0001]. Cannabinoid use combined with psychotic symptoms increased the odds of violence further [odds ratios (OR) 7.1, 95% CI 3.7–13.6; p < 0.0001]. Recent use of cannabinoids with stimulants but without psychotic symptoms was also associated with increased odds of violence (OR 3.3, 95% CI 1.4–7.9; p < 0.0001).
Interpretation
In the emergency setting, patients who have recently used cannabinoids and exhibit psychotic symptoms are at higher risk of violent behaviour. Those who have used both stimulants and cannabinoids without psychotic symptoms may also be at increased risk. De-escalation protocols in emergency healthcare settings should account explicitly for substance use.
Background: Transmission of carbapenemase-producing organisms (CPO) threatens patient safety in healthcare facilities. As a result of a 2011 outbreak of blaKPC+ Klebsiella pneumoniae, the NIH Clinical Center (NIHCC) has prioritized early detection and isolation of CPO carriers, using point-prevalence surveys and targeted high-risk ward surveillance since 2011 and admission surveillance since 2013. We describe our experience over 6 years of admission surveillance. Methods: The NIHCC is a 200-bed research hospital that provides care for a highly immunocompromised patient population. From September 2013 to September 2019, perirectal swabs were ordered automatically for all patients on admission to nonbehavioral health wards. Swabs were ordered twice weekly for ICU patients, weekly in other high-risk wards, and monthly for hospital-wide point prevalence (excluding behavioral health). Patients hospitalized in the United States in the previous week or abroad in the previous 6 months were considered high risk for carriage and isolated pending results from 2 swabs. Most swabs (n = 37,526) were cultured onto HardyCHROM CRE. If gram-negative bacilli (GNB) were present, a molecular screen for carbapenemases was performed on a sweep of cultured material (day 1) pending organism isolation. GNB were identified by MALDI-TOF MS. Prior to June 2019, isolates were screened by blaKPC/blaNDM PCR. Starting in June 2019, Enterobacteriaceae and Pseudomonas aeruginosa were screened using the phenotypic modified carbapenem inactivation method (mCIM), reflexing to the GeneXpert CARBA-R molecular assay if positive; other GNB were tested directly with CARBA-R. Selected GNB underwent susceptibility testing (Sensititre). Whole-genome sequencing was used to assess relatedness among CPO isolates. Swabs from high-risk patients were tested directly by blaKPC PCR (n = 699) until August 2019 (most in parallel with culture) and thereafter by CARBA-R (n = 13). Results: Among 54,188 orders for perirectal swabs, 38,238 were collected from 14,497 patients (compliance 71%). Among 33 CPO-colonized patients identified from September 2013 through September 2019, 15 were identified on admission, 6 were identified in point-prevalence surveys, 8 were identified from high-risk ward surveillance, and 4 were identified from clinical cultures. Sequencing demonstrated no relatedness among CPO isolates. Although only 1.4% of patients sampled on admission were colonized with CPO, those meeting high-risk criteria were 21 times as likely to be colonized. Conclusion: Admission surveillance for CPO identified a low rate of colonization, but it detected nearly half of known CPO-colonized NIHCC patients over the past 6 years. Modest compliance with swab collection leaves room for improvement and likely results in missed instances of colonization. Although we cannot determine its effectiveness, we view our strategy as one of several key safety measures for our highly vulnerable patient population.
Shared patient–clinician decision-making is central to choosing between medical treatments. Decision support tools can have an important role to play in these decisions. We developed a decision support tool for deciding between nonsurgical treatment and surgical total knee replacement for patients with severe knee osteoarthritis. The tool aims to provide likely outcomes of alternative treatments based on predictive models using patient-specific characteristics. To make those models relevant to patients with knee osteoarthritis and their clinicians, we involved patients, family members, patient advocates, clinicians, and researchers as stakeholders in creating the models.
Methods:
Stakeholders were recruited through local arthritis research, advocacy, and clinical organizations. After being provided with brief methodological education sessions, stakeholder views were solicited through quarterly patient or clinician stakeholder panel meetings and incorporated into all aspects of the project.
Results:
Participating in each aspect of the research from determining the outcomes of interest to providing input on the design of the user interface displaying outcome predications, 86% (12/14) of stakeholders remained engaged throughout the project. Stakeholder engagement ensured that the prediction models that form the basis of the Knee Osteoarthritis Mathematical Equipoise Tool and its user interface were relevant for patient–clinician shared decision-making.
Conclusions:
Methodological research has the opportunity to benefit from stakeholder engagement by ensuring that the perspectives of those most impacted by the results are involved in study design and conduct. While additional planning and investments in maintaining stakeholder knowledge and trust may be needed, they are offset by the valuable insights gained.
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.”
Objectives:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Field studies were conducted for 4 yr with HOE-39866 [ammonium-(3-amino-3-carboxypropyl)-methylphosphinate] and for 2 yr with SC-0224 (trimethylsulfonium carboxymethylaminomethylphosphonate) to compare foliar activities with those of paraquat (1,1’-dimethyl-4,4’-bipyridinium ion) and glyphosate [N-(phosphonomethyl)glycine] in no-till corn (Zea mays L. ‘Pioneer 3320’ in 1981 and ‘Pioneer 3184’ in 1982 and 1983). Rates evaluated were 0.6 to 1.7 kg ai/ha for all herbicides except paraquat which was included at 0.3 and 0.6 kg ai/ha. Control of rye (Secale cereale L.) was excellent at all rates with SC-0224, paraquat, and glyphosate, but HOE-39866 was effective only when combined with residual herbicides. All four herbicides provided good initial control of horseweed [Conyza canadensis (L.) Cronq., ♯ ERICA], but recovery following paraquat application was extensive. Combinations of HOE-39866, SC-0224, and glyphosate at 0.6 kg/ha with atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine] at 1.1 to 1.7 kg ai/ha + metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide] at 1.7 kg ai/ha produced antagonistic responses against rye and sometimes horseweed. In 1983, the combination of SC-0224 + residual herbicides provided significantly better control of rye and horseweed 8 days after treatment than the combination of glyphosate + residual herbicides.
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.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.