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.

The digitalisation of mental health care is expected to improve the accessibility and quality of specialised treatment services and introduce innovative methods to study, assess, and monitor mental health disorders. In this narrative review and practical recommendation of the European Psychiatric Association (EPA), we aim to help healthcare providers and policymakers to navigate this rapidly evolving field. We provide an overview of the current scientific and implementation status across two major domains of digitalisation: i) digital mental health interventions and ii) digital phenotyping, discuss the potential of each domain to improve the accessibility and outcomes of mental health services, and highlight current challenges faced by researchers, clinicians, and service users. Furthermore, we make several recommendations meant to foster the widespread adoption of evidence-based digital solutions for mental health care in the member states of the EPA. To realise the vision of a digitalised, patient-centred, and data-driven mental health ecosystem, a number of implementation challenges must be considered and addressed, spanning from human, technical, ethical–legal, and economic barriers. The list of priority areas and action points our expert panel has identified could serve as a playbook for this process.

Mental health service delivery needs radical reimagination in the United States where unmet needs for care remain large and most metrics on the burden of mental health problems have worsened, despite significant numbers of mental health professionals, spending on service provision and research. The COVID-19 pandemic has exacerbated the need for mental health care. One path to a radical reimagination is “Community Initiated Care (CIC)” which equips and empowers communities to address by providing brief psychosocial interventions by people in community settings. We co-developed a theory of change (ToC) for CIC with 24 stakeholders including representatives from community-based, advocacy, philanthropic and faith-based organizations to understand how CIC could be developed and adapted for specific contexts. We present a ToC which describes ways in which the CIC initiative can promote and strengthen mental health in communities in the United States with respect to community organization and leadership; community care and inclusion and normalizing mental health. We propose 10 strategies as part of CIC and propose a way forward for implementation and evaluation. This CIC model is a local, tailored approach which can expand the role of community members to strengthen our response to mental health needs in the United States.

We examined the effect of an antimicrobial stewardship program (ASP), procalcitonin testing and rapid blood-culture identification on hospital mortality in a prospective quality improvement project in critically ill septic adults. Secondarily, we have reported antimicrobial guideline concordance, acceptance of ASP interventions, and antimicrobial and health-resource utilization.

Supporting designers is one of the main motivations for design research. However, there is an ongoing debate about the ability of design research to transfer its results, which are often provided in form of design methods, into practice. This article takes the position that the transfer of design methods alone is not an appropriate indicator for assessing the impact of design research by discussing alternative pathways for impacting design practice. Impact is created by different means – first of all through the students that are trained based on the research results including design methods and tools and by the systematic way of thinking they acquired that comes along with being involved with research in this area. Despite having a considerable impact on practice, this article takes the position that the transfer of methods can be improved by moving from cultivating method menageries to facilitating the evolution of method ecosystems. It explains what is understood by a method ecosystem and discusses implications for developing future design methods and for improving existing methods. This paper takes the position that efforts on improving and maturing existing design methods should be raised to satisfy the needs of designers and to truly support them.

We evaluated the impact of reflex urine culture screen results on antibiotic initiation. More patients with positive urine screen but negative culture received antibiotics than those with a negative screen (30.5 vs 7.1%). Urine screen results may inappropriately influence antibiotic initiation in patients with a low likelihood of infection.

We prove that all transcendental entire functions have infinite topological entropy.

OBJECTIVES/SPECIFIC AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the United States and increases risk for cirrhosis and liver cancer. Identifying modifiable risk factors for NAFLD could allow better targeting of prevention programs. Insulin resistance (IR) plays a significant role in the development and progression of NAFLD. IR is also an important precursor to the development of type 2 diabetes (T2DM). However, the development and duration of IR during young adulthood and its association with NAFLD and T2DM in midlife is unclear. To test whether trajectories of IR using homeostatic model assessment (HOMA-IR) change throughout early adulthood are associated with risk of prevalent NAFLD and T2DM among persons with NAFLD in midlife independent of current or baseline HOMA-IR. METHODS/STUDY POPULATION: Participants from the CARDIA study, a prospective multicenter population-based biracial cohort of adults (baseline age 18–30 years), underwent HOMA-IR measurement (≥8 h fasting and not pregnant) at baseline (1985–1986) and follow-up exam years 7, 10, 15, 20, and 25. At Year 25 (Y25, 2010–2011), liver fat was assessed by noncontrast computed tomography (CT). NAFLD was defined as CT liver attenuation <51 Hounsfield Units after exclusion of other causes of liver fat (alcohol/hepatitis/medications). Latent mixture modeling was used to identify 25-year trajectories in HOMA-IR over time. Multivariable logistic regression models were used to assess associations between HOMA-IR trajectory groups and prevalent NAFLD with adjustment for baseline or Y25 HOMA-IR. RESULTS/ANTICIPATED RESULTS: Among 3060 participants, we identified 3 distinct trajectory groups for HOMA-IR for individuals free from diabetes in middle adulthood: qualitatively low-stable (46.7% of the cohort), moderate-increasing (42.0%), and high-increasing (11.3%) with a NAFLD prevalence at Y25 of: 8.3%, 33.4%, and 63.5%, respectively (p-trend<0.0001). After adjustment for confounders (baseline smoking status, alcohol use, body mass index, physical activity score, systolic blood pressure, antihypertensive medication use, and total/HDL cholesterol ratio) and baseline HOMA-IR, increasing HOMA-IR trajectories were associated with greater NAFLD prevalence compared with the low-stable trajectory group [odds ratio (95% CI): 5.8 (4.3–7.9) and 22.3 (14.2–34.9) for moderate and high, respectively]. These associations were attenuated, but remained significant, even after controlling for current Y25 HOMA-IR [OR=3.6 (2.6–5.0) for moderate and 5.9 (3.4–10.3) for high (referent: low)]. Among participants with NAFLD (n=511), high-increasing HOMA-IR trajectory was associated with greater prevalent [OR=6.5 (1.6–25.7)] and incident [OR=8.7 (2.2–34.4)] T2DM at Y25 independent of confounders and Y25 HOMA-IR (referent: low-stable). DISCUSSION/SIGNIFICANCE OF IMPACT: In this community-based sample of individuals free from diabetes at baseline, an increasing HOMA-IR trajectory through young adulthood was associated with greater NAFLD prevalence in midlife. Knowledge of changes in IR throughout adulthood provides new information on the risk of T2DM among persons with NAFLD in midlife independent of current level of IR. These findings highlight early identification of increasing IR as a potential target for primary prevention of T2DM in the setting of NAFLD.

Dental pulp stem cells (DPSCs) can differentiate into bone cells when provided the correct environment, potentially generating cells to repair non-union fractures. Polylactic Acid (PLA) is a biocompatible polymer for 3-D printing of scaffolds, but DPSCs do not proliferate well on PLA. With the goal of making PLA more conducive for DPSC growth, Graphene Oxide (GO); partially reduced Graphene Oxide (pRGO); GO with iron nanoparticles (FeGO) or Fe-pRGO were incorporated into PLA and spun cast as thin films onto silicon wafers for DPSC plating. DPSCs on Fe-pRGO displayed the fastest doubling time and the highest cell modulus; Fe-pRGO with exterior magnets produced high cell density. SEM demonstrated DPSC mineralization, whereas PLA-only DPSC cultures showed none. Results suggest that PLA/Fe-pRGO and PLA/pRGO enhance DPSC proliferation and possibly differentiation with the potential for use as a 3-D printed scaffold for tissue engineering.

Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.

Until recently, the care of persons with mental disorder in Malta was regulated by mental health legislation enacted in 1976. This was closely modelled on the 1959 British Mental Health Act. Now, the Mental Health Act 2012 is being implemented in two steps, in 2013 and 2014. The paper reviews its provisions.