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A promising approach to assessing research impact draws on the Translational Science Benefits Model (TSBM), an evaluation model that tracks the applied benefits of research in four domains: Clinical and Medical; Community and Public Health; Economic; and Policy and Legislative. However, standardized methods to verify TSBM benefit data, to aid in aggregating impact data within quantitative summaries, do not currently exist.
Methods:
A panel of 11 topic experts participated in a modified Delphi process for establishing content and face validity of a set of criteria for verifying qualitative TSBM data. Two survey rounds were completed by panelists, with a moderated discussion in between rounds to discuss criteria not reaching consensus. Criteria with panel consensus at or above 70% in the survey rounds were confirmed as validated.
Results:
Criteria fell into 9 categories: Content Relevant, Project Related, Who, Reach, What, How, Novel, Documented Evidence, and When. The Delphi process yielded 197 total criteria across the 30 benefits characterized by the TSBM (range = 5–8 criteria per benefit).
Discussion:
The results of this Delphi process lay the foundation for developing a TSBM coding tool for evaluating and quantifying TSBM data. Standardizing this process will enable data aggregation, group analysis, and the comparison of research impact across contexts.
Syncope is common among pediatric patients and is rarely pathologic. The mechanisms for symptoms during exercise are less well understood than the resting mechanisms. Additionally, inert gas rebreathing analysis, a non-invasive examination of haemodynamics including cardiac output, has not previously been studied in youth with neurocardiogenic syncope.
Methods:
This was a retrospective (2017–2023), single-center cohort study in pediatric patients ≤ 21 years with prior peri-exertional syncope evaluated with echocardiography and cardiopulmonary exercise testing with inert gas rebreathing analysis performed on the same day. Patients with and without symptoms during or immediately following exercise were noted.
Results:
Of the 101 patients (15.2 ± 2.3 years; 31% male), there were 22 patients with symptoms during exercise testing or recovery. Resting echocardiography stroke volume correlated with resting (r = 0.53, p < 0.0001) and peak stroke volume (r = 0.32, p = 0.009) by inert gas rebreathing and with peak oxygen pulse (r = 0.61, p < 0.0001). Patients with syncopal symptoms peri-exercise had lower left ventricular end-diastolic volume (Z-score –1.2 ± 1.3 vs. –0.36 ± 1.3, p = 0.01) and end-systolic volume (Z-score –1.0 ± 1.4 vs. −0.1 ± 1.1, p = 0.001) by echocardiography, lower percent predicted peak oxygen pulse during exercise (95.5 ± 14.0 vs. 104.6 ± 18.5%, p = 0.04), and slower post-exercise heart rate recovery (31.0 ± 12.7 vs. 37.8 ± 13.2 bpm, p = 0.03).
Discussion:
Among youth with a history of peri-exertional syncope, those who become syncopal with exercise testing have lower left ventricular volumes at rest, decreased peak oxygen pulse, and slower heart rate recovery after exercise than those who remain asymptomatic. Peak oxygen pulse and resting stroke volume on inert gas rebreathing are associated with stroke volume on echocardiogram.
In a prospective, remote natural history study of 277 individuals with (60) and genetically at risk for (217) Parkinson’s disease (PD), we examined interest in the return of individual research results (IRRs) and compared characteristics of those who opted for versus against the return of IRRs. Most (n = 180, 65%) requested sharing of IRRs with either a primary care provider, neurologist, or themselves. Among individuals without PD, those who requested sharing of IRRs with a clinician reported more motor symptoms than those who did not request any sharing (mean (SD) 2.2 (4.0) versus 0.7 (1.5)). Participant interest in the return of IRRs is strong.
The Conyza genus includes nearly 150 species, comprising closely related weedy species. Proper identification of Conyza spp. is essential to develop effective strategies for their management. The overlap of traits, species varieties, and the putative occurrence of hybridization hampers the identification of Conyza spp. and its management in agricultural and natural environments. Herein, we assessed five DNA barcodes and 32 morphological traits to classify Conyza spp. and survey their dispersion in soybean fields [Glycine max (L.) Merr.] in Brazil in 2019, 2020, and 2021. The Conyza accessions included two species, hairy fleabane [Conyza bonariensis (L.) Cronquist) and Sumatran fleabane [Conyza sumatrensis (Retz.) E. Walker], and each species comprised two varieties. The ITS and rps16-trnQ gene regions showed the ability to distinguish between the two Conyza species, while the matK, rbcL, and trnF-trnF gene regions were not polymorphic. Out of 32 morphological traits, phyllary color, involucre shape, capitulescence type, and inflorescence type were the most polymorphic and even reliable for taxonomic purposes. The combination of ITS or ITS+rps16-trnQ regions and the four morphological markers was able to discriminate 91% of the plants, except those of C. bonariensis var. angustifolia. These results support the taxonomic resolution between C. bonariensis and C. sumatrensis and are useful for other Conyza spp. and other closely related weedy species worldwide. Conyza sumatrensis was detected in 94% of soybean fields across macroregions and seasons in Brazil, while C. bonariensis was sparsely dispersed, mainly in the southern macroregion (MRS 1).
The coronavirus disease 2019 (COVID-19) pandemic deleteriously impacted physical and mental health. In the summer of 2020, return-to-learn plans were enacted, including virtual, hybrid, and in-person plans, impacting educators and students. We examined (1) how return-to-learn plan was related to depressive and social anxiety symptoms among educators and (2) how psychological flexibility related to symptoms.
Methods:
Educators (N = 853) completed a survey via Qualtrics that assessed internalizing symptoms, psychological flexibility, and occupational characteristics. Two one-way analyses of variance (ANOVAs) examined between-group differences in return-to-learn plans across depression and social anxiety. Two hierarchical linear regressions examined the relation between psychological flexibility components and depressive and social anxiety symptoms.
Results:
Median T-scores were well above the national normative means for General Depression (median T-score: 81) and Social Anxiety (median T-score: 67). There were no significant differences between reopening plans in general depression nor social anxiety T-scores. Psychological flexibility accounted for 33% of the variance in depressive symptoms and 24% of the variance in social anxiety symptoms.
Conclusions:
Results indicated high levels of psychiatric symptoms among educators during COVID-19, and psychological flexibility was associated with lower symptoms. Addressing educator mental health is of utmost importance in future research.
Nonlinear simulations of Alfvén modes (AMs) driven by energetic particles (EPs) in the presence of turbulence are performed with the gyrokinetic particle-in-cell code ORB5. The AMs carry a heat flux, and consequently they nonlinearly modify the plasma temperature profiles. The isolated effect of this modification on the dynamics of turbulence is studied by means of electrostatic simulations. We find that turbulence is reduced when the profiles relaxed by the AM are used, with respect to the simulation where the unperturbed profiles are used. This is an example of indirect interaction of EPs and turbulence. First, an analytic magnetic equilibrium with circular concentric flux surfaces is considered as a simplified example for this study. Then, an application to an experimentally relevant case of ASDEX Upgrade is discussed.
In this work, we revisit the linear gyro-kinetic theory of geodesic acoustic modes (GAMs) and derive a general dispersion relation for an arbitrary equilibrium distribution function of ions. A bi-Maxwellian distribution of ions is then used to study the effects of ion temperature anisotropy on GAM frequency and growth rate. We find that ion temperature anisotropy yields sensible modifications to both the GAM frequency and growth rate as both tend to increase with anisotropy and these results are strongly affected by the electron to ion temperature ratio.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, ‘conventional’ meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis.
Aims
We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891).
Method
We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies.
Conclusions
This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.
We aimed at evaluating the association of maternal pre-pregnancy nutritional status with offspring anthropometry and body composition. We also evaluated whether these associations were modified by gender, diet and physical activity and mediated by birth weight.
Design:
Birth cohort study.
Setting:
Waist circumference was measured with an inextensible tape, and fat and lean mass were measured using dual-energy X-ray absorptiometry. Multiple linear regression was used to adjust for possible confounders and allele score of BMI. We carried out mediation analysis using G-formula.
Participants:
In 1982, 1993 and 2004, all maternity hospitals in Pelotas (South Brazil) were visited daily and all live births whose families lived in the urban area of the city were evaluated. These subjects have been followed up at different ages.
Results:
Offspring of obese mothers had on average higher BMI, waist circumference and fat mass index than those of normal weight mothers, and these differences were higher among daughters. The magnitudes of the association were similar in the cohorts, except for height, where the association pattern was not clear. In the 1982 cohort, further adjustment for a BMI allele score had no material influence on the magnitude of the associations. Mediation analyses showed that birth weight captured part of this association.
Conclusions:
Our findings suggest that maternal pre-pregnancy nutritional status is positively associated with offspring BMI and adiposity in offspring. And this association is higher among daughters whose mother was overweight or obese and, birth weight explains part of this association.
This article emerged as the human species collectively have been experiencing the worst global pandemic in a century. With a long view of the ecological, economic, social, and political factors that promote the emergence and spread of infectious disease, archaeologists are well positioned to examine the antecedents of the present crisis. In this article, we bring together a variety of perspectives on the issues surrounding the emergence, spread, and effects of disease in both the Americas and Afro-Eurasian contexts. Recognizing that human populations most severely impacted by COVID-19 are typically descendants of marginalized groups, we investigate pre- and postcontact disease vectors among Indigenous and Black communities in North America, outlining the systemic impacts of diseases and the conditions that exacerbate their spread. We look at how material culture both reflects and changes as a result of social transformations brought about by disease, the insights that paleopathology provides about the ancient human condition, and the impacts of ancient globalization on the spread of disease worldwide. By understanding the differential effects of past epidemics on diverse communities and contributing to more equitable sociopolitical agendas, archaeology can play a key role in helping to pursue a more just future.
Bodenhorn et al. (2017) have sparked considerable controversy by arguing that the fall in adult stature observed in military samples in the United States and Britain during industrialization was a figment of selection on unobservables in the samples. While subsequent papers have questioned the extent of the bias (Komlos and A’Hearn 2019; Zimran 2019), there is renewed concern about selection bias in historical anthropometric datasets. Therefore, this article extends Bodenhorn et al.’s discussion of selection bias on unobservables to sources of children’s growth, specifically focusing on biases that could distort the age pattern of growth. Understanding how the growth pattern of children has changed is important because these changes underpinned the secular increase in adult stature and are related to child stunting observed in developing countries today. However, there are significant sources of unobserved selection in historical datasets containing children’s and adolescents’ height and weight. This article highlights, among others, three common sources of bias: (1) positive selection of children into secondary school in the late nineteenth and early twentieth centuries; (2) distorted height by age profiles created by age thresholds for enlistment in the military; and (3) changing institutional ecology that determines to which institutions children are sent. Accounting for these biases adjusts the literature in two ways: evidence of a strong pubertal growth spurt in the nineteenth century is weaker than formerly acknowledged and some long-run analyses of changes in children’s growth are too biased to be informative, especially for Japan.
Attempts to reduce high utilisation of psychiatric inpatient care by targeting the critical time of hospital discharge have been rare. In Germany, until now no such intervention has been implemented, let alone subjected to a clinical trial.
Method
“Effectiveness and Cost-Effectiveness of Needs-Oriented Discharge Planning and Monitoring for High Utilisers of Psychiatric Services” (NODPAM) is a multicentre RCT conducted in five psychiatric hospitals in Germany (Günzburg, Düsseldorf, Regensburg, Greifswald, and Ravensburg). Subjects asked to provide informed consent to participate have to be of adult age with a primary diagnosis of schizophrenia or affective disorder, and a defined high utilisation of psychiatric care during two years prior to the current admission. Subjects are asked to provide detailed outcome data at four measurement points during a period of 18 months. Recruitment (which started in April 06) is still ongoing. Thus, baseline data of about 350 participants will be presented.
Results
Recruitment has been quite successful and the study has been generally well accepted by participating patients and their clinicians in in- and outpatient treatment settings. Subjects showed substantial initial impairment on outcome measures (e.g. needs, psychopathology, quality of life, and level of functioning) and high utilisation of mental health care. Further results on conduct and feasibility of the trial will be presented.
Conclusions
The first phase of this mulicentre trial was promising. The potential of this study to strengthen the integration of mental health care provision in Germany will be discussed.
Family and twin studies point towards a partial heritability of suicidal behavior. We investigated the role of a comprehensive set of genes in this behavior. Their selection was driven by results from post mortem and genetic studies. 250 suicide attempters with various psychiatric disorders were compared with 2200 volunteers which were randomly selected from the general population. All subjects were administered standard psychiatric interviews including SCID as well as self-report questionnaires for anger-related traits. Especially, aggressive-impulsive behavior has been studied and associations with these intermediate phenotypes will be presented.
Additionally a large-scale gene expression analysis using cDNA-microarrays to identify new candidate-genes for suicide was conducted. We found several genes to be differentially expressed in the orbitofrontal cortex of suicide completers. Cross-validation experiments using quantitative RT-PCR validated a few genes so far. These genes have been genotyped in our patients and controls and associations with suicidal behavior and intermediate phenotypes, like aggression and impulsivity will be presented.
The SNAP-25 gene is an integral part of the vesicle docking and fusion machinery that controls the neurotransmitter release from the vesicles of the presynaptic neuron into the synaptic cleft. Several post mortem studies revealed a reduction of SNAP-25 protein in the hippocampus of patients with schizophrenia and bipolar disorder.
Methods:
38 patients with schizophrenia, bipolar disorder or obsessive-compulsive disorder and 15 healthy controls participated in the study. Proton magnetic resonance spectroscopy in left hippocampus was performed in each individual. Three single nucleotide polymorphisms (SNP) of the SNAP-25 gene were genotyped.
Results:
Individuals with the homozygous CC genotype of the DdeI SNP presented a significantly higher ratio of NAA/Cho in the left hippocampus compared to the group of individuals with the homozygous TT genotype.
Conclusions:
The present findings are consistent with the view that the SNAP-25 genotype may modulate synaptic plasticity and neurogenesis in the left hippocampus, and that an altered NAA/Cho ratio may be an indicator for this genetic modulation of neuronal function in the hippocampus.
Khat consumption is widespread in Yemeni society and causes problems both in economic development and public health. The gender-specific motives for khat use and abstinence were studied to create a toe-hold for more specific interventions.
Methods
In a sample with equal numbers of males, females, abstainers and consumers, 320 subjects were interviewed on their specific opinions about khat and its impact on subjective and public health, and on social and community functioning. Strata were compared in their acceptance and denial of opinions. Notions that could predict abstinence status or gender were identified with multivariate logistic regression analysis.
Results
Male khat users had a strong identification with khat use, while females were more ambivalent. The notion that khat consumption is a bad habit (odds ratio (OR) 3.4) and consumers are malnuorished (OR 2.2) were associated with female gender among khat users. Among the females worries about health impact (OR 3.2) and loss of esteem in the family (OR 3.1) when using khat predicted abstinence. Male abstainers opposed khat users in the belief that khat is the cause of social problems (OR 5.1).
Conclusions
Distinct beliefs allow a differentiation between males, females, khat users and abstainers when targeting preventive measures. In accordance to their specific values female khat users are most ambivalent towards their habit. Positive opinions scored lower than expected in the consumers. Public opinion towards khat may have become slightl more negative in recent years. This finding creates a strong toe-hold for gender-specific public health interventions.