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In 2024, the U.S. Government introduced, and then quickly rescinded, a new policy to oversee Dual Use Research of Concern (DURC) and Pathogens with Enhanced Pandemic Potential (PEPP). This research explores how biosafety practitioners interpreted and assessed the policy itself and discussed challenges to implementation. An inductive, grounded theory approach was used to identify key insights from qualitative data generated at a 2-day deliberative workshop with 45 biosafety officers, compliance professionals and researchers; analysis was supported using NVivo software. Participants described the policy’s ambiguous language, lack of actionable federal guidance, limited legal scope and unfunded administrative burdens as significant barriers to implementation. Although supportive of the policy’s goals, workshop participants stressed the need for more precise definitions, practical examples and practitioner-informed implementation strategies. The findings demonstrate that durable and effective biosafety and biosecurity oversight requires early, substantive engagement with those operationalizing policy.
Assessing children’s diets is currently challenging and burdensome. Abbreviated FFQ have the potential to assess dietary patterns in a rapid and standardised manner. Using nationally representative UK dietary intake and biomarker data, we developed an abbreviated FFQ to calculate dietary quality scores for pre-school and primary school-aged children. UK National Diet and Nutrition Survey (2008–2016) weekly consumption frequencies of 129 food groups from 4-d diaries were cross-sectionally analysed using principal component analysis. A 129-item score was derived, alongside a 12-item score based on foods with the six highest and six lowest coefficients. Participants included 1069 pre-schoolers and 2565 primary schoolchildren. The first principal component explained 3·4 and 3·0 % of the variation in the original diet variables for pre-school and primary school groups, respectively, and described a prudent diet pattern. Prudent diet scores were characterised by greater consumption of fruit, vegetables and tap water and lower consumption of crisps, manufactured coated chicken/turkey products, purchased chips and soft drinks for both age groups. Correlations between the 129-item and 12-item scores were 0·86 and 0·84 for pre-school and primary school-aged children, respectively. Bland–Altman mean differences between the scores were 0·00 sd; 95 % limits of agreement were −1·05 to 1·05 and −1·10 to 1·10 sd for pre-school and primary school-aged children, respectively. Correlations between dietary scores and nutritional biomarkers showed only minor attenuation for the 12-item compared with the 129-item scores, illustrating acceptable congruence between prudent diet scores. The two 12-item FFQ offer user-friendly tools to measure dietary quality among UK children.
The translational science workforce requires preparation in both core skills for biomedical research and competencies for advancing progress along the translational pipeline. Delivering this content in a highly accessible manner will help expand and diversify the workforce.
Methods:
The NCATS Education Branch offers online case study-based courses in translational science for a general scientific audience. The branch updated its course in preclinical translational science with additional content aligned with the NCATS Translational Science Principles, which characterize effective approaches to advance translation. The updated course was offered in 2021 and 2022. The branch also revised the course evaluation to capture knowledge change aligned with the NCATS Translational Science Principles.
Results:
Of 106 students, 88 completed baseline or endpoint surveys, with 48 completing both. Most found the online format (n = 48; 91%) and case study approach (n = 48; 91%) effective. There was a statistically significant increase in knowledge related to the Translational Science Principles (p < 0.001). Survey items with the highest endpoint scores reflected the principles on creativity and innovation, efficiency, cross-disciplinary team science, and boundary-crossing collaborations. Findings highlighted the effectiveness of pairing a case study with lectures that offer generalizable strategies aligned with the translational science principles. Students reported the course helped them learn about the trajectory of a drug discovery and development initiative, where their own work fit in, and scientific and operational approaches to apply in their own work.
Conclusions:
This online case study-based course was effective in teaching generalizable principles for translational science to students with varied scientific backgrounds.
Plant growth requires the integration of internal and external cues, perceived and transduced into a developmental programme of cell division, elongation and wall thickening. Mechanical forces contribute to this regulation, and thigmomorphogenesis typically includes reducing stem height, increasing stem diameter, and a canonical transcriptomic response. We present data on a bZIP transcription factor involved in this process in grasses. Brachypodium distachyon SECONDARY WALL INTERACTING bZIP (SWIZ) protein translocated into the nucleus following mechanostimulation. Classical touch-responsive genes were upregulated in B. distachyon roots following touch, including significant induction of the glycoside hydrolase 17 family, which may be unique to grass thigmomorphogenesis. SWIZ protein binding to an E-box variant in exons and introns was associated with immediate activation followed by repression of gene expression. SWIZ overexpression resulted in plants with reduced stem and root elongation. These data further define plant touch-responsive transcriptomics and physiology, offering insights into grass mechanotranduction dynamics.
Preliminary work suggests anxiety moderates the relationship between irritability and bullying. As anxiety increases, the link between irritability and perpetration decreases. We hypothesize that any moderation effect of anxiety is driven by social anxiety symptoms. We sought to explicate the moderating effect of anxiety, while clarifying relations to other aggressive behaviors.
Methods:
A sample of adolescents (n = 169, mean = 12.42 years of age) were assessed using clinician rated assessments of anxiety, parent reports of irritability and bullying behaviors (perpetration, generalized aggression, and victimization). Correlations assessed zero-order relations between variables, and regression-based moderation analyses were used to test interactions. Johnson–Neyman methods were used to represent significant interactions.
Results:
Irritability was significantly related to bullying (r = .403, p < .001). Social, but not generalized, anxiety symptoms significantly moderated the effect of irritability on bully perpetration (t(160) = −2.94, b = −.01, p = .0038, ΔR2 = .0229, F(1, 160) = 8.635). As social anxiety symptoms increase, the link between irritability and perpetration decreases.
Conclusions:
Understanding how psychopathology interacts with social behaviors is of great importance. Higher social anxiety is linked to reduced relations between irritability and bullying; however, the link between irritability and other aggression remains positive. Comprehensively assessing how treatment of psychopathology impacts social behaviors may improve future intervention.
The effects of reaction time (2 to 72 h) and NH4+/A13+ molar ratio (1.6, 2.4 and 3.2) on the hydrothermal synthesis of ammonium-saponites are investigated. The gels are obtained by mixing powders, resulting in a stoichiometric composition, Mg3Si34Al0.6O10(OH)2, with aqueous ammonium solutions, with and without F, to result in initial NH4+/Al3+ molar ratios of 1.6, 2.4 and 3.2. The solid bulk products are characterized by X-raydiffraction (XRD), X-ray fluorescence (XRF) and scanning electron microscopy (SEM) combined with energy-dispersive X-ray (EDX) analysis. The cation exchange capacity (CEC) is determined with an ammonia selective electrode and the pH of the water from the first washing is measured. Ammonium-saponite is formed rapidly within 16 h. A higher NH4+/A13+ molar ratio and the presence of F facilitate the crystallization of saponite. Small metastable amounts of bayerite, Al(OH)3, are present at low NH4+/A13+ molar ratios; after short reaction times, they disappear. During the first 4 h, the pH decreases rapidly, then drops slowly to a constant level of approximately 4.6 after 60 h. With increasing reaction time, saponite crystallites grow in the ab directions of the individual sheets with almost no stacking to thicker flakes. The NH4+ CEC of the solid products increases strongly within the first 24 h. A maximum of 53.3 meq/100 g is observed. The saponite yield increases from approximately 25% after 2 h to almost 100% after 72 h.
Difficulties with emotion regulation are integral to borderline personality disorder (BPD) and its hypothesized developmental pathway. Here, we prospectively assess trajectories of emotion processing across childhood, how BPD symptoms impact these trajectories, and whether developmental changes are transdiagnostic or specific to BPD, as major depressive (MDD) and conduct disorders (CD) are also characterized by emotion regulation difficulties. This study included 187 children enriched for those with early symptoms of depression and disruptive behaviors from a longitudinal study. We created multilevel models of multiple components of emotional processing from mean ages 9.05 to 18.55 years, and assessed the effect of late adolescent BPD, MDD, and CD symptoms on these trajectories. Linear trajectories of coping with sadness and anger, and quadratic trajectories of dysregulated expressions of sadness and anger were transdiagnostic, but also exhibited independent relationships with BPD symptoms. Only inhibition of sadness was related to BPD symptoms. The quadratic trajectories of poor emotional awareness and emotional reluctance were also independently related to BPD. Findings support examining separable components of emotion processing across development as potential precursors to BPD, underscoring the importance of understanding these trajectories as not only a marker of potential risk but also potential targets for prevention and intervention.
The National Center for Advancing Translational Science (NCATS) seeks to improve upon the translational process to advance research and treatment across all diseases and conditions and bring these interventions to all who need them. Addressing the racial/ethnic health disparities and health inequities that persist in screening, diagnosis, treatment, and health outcomes (e.g., morbidity, mortality) is central to NCATS’ mission to deliver more interventions to all people more quickly. Working toward this goal will require enhancing diversity, equity, inclusion, and accessibility (DEIA) in the translational workforce and in research conducted across the translational continuum, to support health equity. This paper discusses how aspects of DEIA are integral to the mission of translational science (TS). It describes recent NIH and NCATS efforts to advance DEIA in the TS workforce and in the research we support. Additionally, NCATS is developing approaches to apply a lens of DEIA in its activities and research – with relevance to the activities of the TS community – and will elucidate these approaches through related examples of NCATS-led, partnered, and supported activities, working toward the Center’s goal of bringing more treatments to all people more quickly.
Social connectedness might positively influence the course of clinical symptoms in people with psychotic disorders.
Objectives
This study examines satisfaction with social connectedness (SSC) as predictor of positive and negative symptoms in people with a psychotic disorder.
Methods
Data from the Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS, 2014-2019) was used from patients diagnosed with a psychotic disorder (N=2109). Items about social connectedness of the Manchester short assessment of Quality of Life (ManSA) were used to measure SSC. Linear mixed models were used to estimate the association of SSC with the Positive and Negative Syndrome Scale (PANSS) after one and two years against α=0.01. Analyses were adjusted for symptoms, time since onset, gender and age. Additionally, fluctuation of positive and negative symptom scores over time was estimated.
Results
Mean duration of illness of the sample was 18.8 years (SD 10.7) with >65% showing only small variation in positive and negative symptoms over a two to five-year time period. After adjustment for covariates, SSC showed to be negatively associated with positive symptoms after one year (β=-0.47, p<0.001, 95% CI=-0.70,-0.25) and two years (β =-0.59, p<0.001, 95% CI = -0.88,-0.30), and for negative symptoms after one year (β=-0.52, p<0.001, 95% CI = -0.77,-0.27). The prediction of negative symptoms was not significant at two years.
Conclusions
This research indicates that interventions on SSC might positively impact mental health for people with psychosis. SSC is a small and robust predictor of future levels of positive symptoms. Negative symptoms could be predicted by SSC at one year.
There is increasing interest in modelling longitudinal dietary data and classifying individuals into subgroups (latent classes) who follow similar trajectories over time. These trajectories could identify population groups and time points amenable to dietary interventions. This paper aimed to provide a comparison and overview of two latent class methods: group-based trajectory modelling (GBTM) and growth mixture modelling (GMM). Data from 2963 mother–child dyads from the longitudinal Southampton Women’s Survey were analysed. Continuous diet quality indices (DQI) were derived using principal component analysis from interviewer-administered FFQ collected in mothers pre-pregnancy, at 11- and 34-week gestation, and in offspring at 6 and 12 months and 3, 6–7 and 8–9 years. A forward modelling approach from 1 to 6 classes was used to identify the optimal number of DQI latent classes. Models were assessed using the Akaike and Bayesian information criteria, probability of class assignment, ratio of the odds of correct classification, group membership and entropy. Both methods suggested that five classes were optimal, with a strong correlation (Spearman’s = 0·98) between class assignment for the two methods. The dietary trajectories were categorised as stable with horizontal lines and were defined as poor (GMM = 4 % and GBTM = 5 %), poor-medium (23 %, 23 %), medium (39 %, 39 %), medium-better (27 %, 28 %) and best (7 %, 6 %). Both GBTM and GMM are suitable for identifying dietary trajectories. GBTM is recommended as it is computationally less intensive, but results could be confirmed using GMM. The stability of the diet quality trajectories from pre-pregnancy underlines the importance of promotion of dietary improvements from preconception onwards.
There is a need for education activities in translational science (TS) that focus on teaching key principles, concepts, and approaches to effectively overcome common scientific and operational bottlenecks in the translational process. Delivering this content to the broad range of individuals interested in advancing translation will help to both expand and develop the TS workforce. Rigorous evaluations will build the evidence base for effective educational approaches for varied audiences.
Methods:
In 2020, the National Center for Advancing Translational Sciences offered an online case study-based course in TS for students across education and career stages. The course evaluation used baseline and endpoint student surveys to assess satisfaction with the course and impacts of participation on knowledge and attitudes relevant to TS and professional goals.
Results:
Of 112 students, 100 completed baseline and/or endpoint surveys, with 66 completing both. Most found the online format (n = 59, 83%) and case study approach (n = 62, 87%) moderately or very effective. There were statistically significant increases in TS knowledge (P < .001) and positive attitudes about team science in translational research (TR) (P < .001). Students reported the course increased their skills and knowledge in cross-disciplinary team science, the process of preclinical and clinical TR, and how their work fits into the translational spectrum, and increased their interest in scientific approaches used in the case study and careers in TS, TR, or team science.
Conclusions:
This online case study-based course effectively conveyed TS concepts to students from a range of backgrounds and enhanced their professional interests related to course content.
In 2008, the Chinese government created the Thousand Talents Program (TTP) to recruit overseas expertise to build up China’s science and technology knowledge and innovation base. Ten years later, in 2018, the Federal Bureau of Investigation (FBI) announced a new “China Initiative” that aimed to counter the transfer by U.S.-based scientists involved in the TTP of knowledge and intellectual property that could support China’s military and economic might and pose threats to U.S. national security. This initiative launched a number of investigations into major U.S. federal funding agencies and universities and charged several scientists, many of them life scientists, with failing to accurately report their work and affiliations with Chinese entities and illegally transferring scientific information to China. Although the FBI cases demonstrate a clear problem with disclosure of foreign contracts and research integrity among some TTP recipients, they have failed to demonstrate any harm to U.S. national security interests. At the heart of this controversy are core questions that remain unresolved and need more attention: What is required to transfer and develop knowledge to further a country’s science and technology ambitions? And can the knowledge acquired by a visiting scientist be easily used to further a country’s ambitions? Drawing on literature from the field of science and technology studies, this article discusses the key issues that should be considered in evaluating this question in the Chinese context and the potential scientific, intelligence, and policy implications of knowledge transfer as it relates to the TTP.
Temper tantrums are sudden, overt negative emotional displays that are disproportionate to the eliciting event. Research supports that severe temper tantrums during the preschool period are associated with preschool psychopathology, but few studies have identified which characteristics of preschool tantrums are predictive of distal psychopathological outcomes in later childhood and adolescence. To examine this question, we used a prospective, longitudinal dataset enriched for early psychopathology. Participants (N = 299) included 3-to 6-year-old children (47.8% female) assessed for tantrums and early childhood psychopathology using diagnostic interviews and then continually assessed using diagnostic interviews over 10 subsequent time points throughout childhood and adolescence. We identified two unique groupings of tantrum behaviors: aggression towards others/objects (e.g., hitting others) and aggression towards self (e.g., hitting self). While both types of tantrum behaviors were associated with early childhood psychopathology severity, tantrum behaviors characterized by aggression towards self were more predictive of later psychopathology. Children displaying high levels of both types of tantrum behaviors had more severe externalizing problems during early childhood and more severe depression and oppositional defiant disorder across childhood and adolescence. Findings suggest that tantrum behaviors characterized by aggression towards self are particularly predictive of later psychopathology.
There are numerous examples of translational science innovations addressing challenges in the translational process, accelerating progress along the translational spectrum, and generating solutions relevant to a wide range of human health needs. Examining these successes through an education lens can identify core principles and effective practices that lead to successful translational outcomes. The National Center for Advancing Translational Sciences (NCATS) is identifying and teaching these core principles and practices to a broad audience via online courses in translational science which teach from case studies of NCATS-led or supported research initiatives. In this paper, we share our approach to the design of these courses and offer a detailed description of our initial course, which focused on a preclinical drug discovery and development project spanning academic and government settings. Course participants were from a variety of career stages and institutions. Participants rated the course high in overall value to them and in providing a unique window into the translational science process. We share our model for course development as well as initial findings from the course evaluation with the goal of continuing to stimulate development of novel education activities teaching foundational principles in translational science to a broad audience.
Interdisciplinary engineering of cyber physical production systems (CPPS) are often subject to delay, cost overrun and quality problems or may even fail due to the lack of efficient information exchange between multiple interdisciplinary teams working in complex networks within and across companies. We propose a direct integration of multiteam and organisational aspects into the graphical notation of the systems engineering workflow. BPMN++, with eight new notational elements and two subdiagrams, enables the modelling of the required cooperation aspects. BPMN++ provides an improved overview, uniform notation, more compact presentation and easier modifiability from an engineering point of view. We also included a first set of empirical studies and historical qualitative and quantitative data in addition to subjective expert-based ratings to increase validity. The use case introduced to explain the procedure and the notation is derived from surveys in plant manufacturing focussing on the start-up phase and decision support at site. This, in particular, is one of the most complex and critical phases with potentially high economic impact. For evaluation purposes, we compare two alternative solutions for a short-term management decision in the start-up phase of CPPS using the BPMN++ approach.
Emotion dysregulation is cross-diagnostic and impairing. Most research has focused on dysregulated expressions of negative affect, often measured as irritability, which is associated with multiple forms of psychopathology and predicts negative outcomes. However, the Research Domain Criteria (RDoC) include both negative and positive valence systems. Emerging evidence suggests that dysregulated expressions of positive affect, or excitability, in early childhood predict later psychopathology and impairment above and beyond irritability. Typically, irritability declines from early through middle childhood; however, the developmental trajectory of excitability is unknown. The impact of excitability across childhood on later emotion dysregulation is also yet unknown. In a well-characterized, longitudinal sample of 129 children studied from ages 3 to 5.11 years through 14 to 19 years, enriched for early depression and disruptive symptoms, we assessed the trajectory of irritability and excitability using multilevel modeling and how components of these trajectories impact later emotion dysregulation. While irritability declines across childhood, excitability remains remarkably stable both within and across the group. Overall levels of excitability (excitability intercept) predict later emotion dysregulation as measured by parent and self-report and predict decreased functional magnetic resonance imaging activity in cognitive emotion regulation regions during an emotion regulation task. Irritability was not related to any dysregulation outcome above and beyond excitability.
Opium tincture (OT) is widely used for opioid substitution treatment (OST) in Iran.
Objectives
To determine if OT is a safe and effective medication for OST.
Methods
Opium Trial was a multicenter, double‐blind, noninferiority randomized controlled trial, with 204 participants with opioid dependence in Iran. Participants were then randomized to OT or methadone arms with an allocation ratio of 1:1 and were followed for 12 weeks. The primary outcome was retention in treatment, compared between the two groups using both intention-To-Treat (ITT) and Per-Protocol (PP) analyses.
Results
A total of 70 participants (IT: 68.6%, PP: 69.3%) in methadone arm and 61 participants (ITT: 59.8%, PP: 60.4%) in OT arm remained in the treatment. The relative retention rate was 1.15 (0.97, 1.36) in both analyses in favour of methadone. A total of 46 out of 152 (30.3%) participants in OT arm and 83 out of 168 (49.4%) participants in methadone arm reported opioid use outside the treatment. The difference in these two proportions (OT - methadone) was 19%: (10%, 28%) in favour of OT. The proportion of patients with adverse events were not different between the two arms (P = 0.06). There was no serious AE in OT arm.
Conclusions
Opium tincture is a clinically effective and safe medication, but this study could not conclude if it was as equally effective as methadone in retaining participants in treatment, but it showed that OT was superior to methadone in reducing opioid use outside the treatment.
The internal research program of the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health aims to fundamentally transform the preclinical translational research process to get more treatments to more people more quickly. The program develops and implements innovative scientific and operational approaches that accelerate and enhance translation across many diverse projects. Cross-disciplinary team science is a defining feature of our organization, with scientists at all levels engaged in multiple research teams. Here, we share our systems approach to nurturing cross-disciplinary team science, which leverages organizational policies, structures, and processes. Policies including the organizational mission statement, principles for ethical conduct of research, performance review criteria, and training program objectives and approaches reinforce the value of team science to achieve the program’s scientific goals. Structures including an organizational structure designed around solving translational problems, co-location of employees in a single state-of-the-art scientific facility, and shared-use laboratories, expertise and instrumentation facilitate collaboration. Processes including fluid team assembly, specialized project management, cross-agency partnerships, and decision making based on clear screening criteria and milestones enable effective team assembly and functioning. We share evidence of the impact of these approaches on the science and commercialization of findings and discuss pathways to broad adoption of similar approaches.
Violent criminal offenders with personality disorders (PD's) can cause immense harm, but are often deemed untreatable. This study aimed to conduct a randomized clinical trial to test the effectiveness of long-term psychotherapy for rehabilitating offenders with PDs.
Methods
We compared schema therapy (ST), an evidence-based psychotherapy for PDs, to treatment-as-usual (TAU) at eight high-security forensic hospitals in the Netherlands. Patients in both conditions received multiple treatment modalities and differed only in the individual, study-specific therapy they received. One-hundred-three male offenders with antisocial, narcissistic, borderline, or paranoid PDs, or Cluster B PD-not-otherwise-specified, were assigned to 3 years of ST or TAU and assessed every 6 months. Primary outcomes were rehabilitation, involving gradual reintegration into the community, and PD symptoms.
Results
Patients in both conditions showed moderate to large improvements in outcomes. ST was superior to TAU on both primary outcomes – rehabilitation (i.e. attaining supervised and unsupervised leave) and PD symptoms – and six of nine secondary outcomes, with small to moderate advantages over TAU. ST patients moved more rapidly through rehabilitation (supervised leave, treatment*time: F(5308) = 9.40, p < 0.001; unsupervised leave, treatment*time: F(5472) = 3.45, p = 0.004), and showed faster improvements on PD scales (treatment*time: t(1387) = −2.85, p = 0.005).
Conclusions
These findings contradict pessimistic views on the treatability of violent offenders with PDs, and support the effectiveness of long-term psychotherapy for rehabilitating these patients, facilitating their re-entry into the community.