A conserved polar residue plays a critical role in mismatch detection in A-family DNA polymerases.

In A-family DNA polymerases (dPols), a functional 3'-5' exonuclease activity is known to proofread newly synthesized DNA. The identification of a mismatch in substrate DNA leads to transfer of the primer strand from the polymerase active site to the exonuclease active site. To shed more light regarding the mechanism responsible for the detection of mismatches, we have utilized DNA polymerase 1 from Aquifex pyrophilus (ApPol1). The enzyme synthesized DNA with high fidelity and exhibited maximal exonuclease activity with DNA substrates bearing mismatches at the -2 and - 3 positions. The crystal structure of apo-ApPol1 was utilized to generate a computational model of the functional ternary complex of this enzyme. The analysis of the model showed that N332 forms interactions with minor groove atoms of the base pairs at the -2 and - 3 positions. The majority of known A-family dPols show the presence of Asn at a position equivalent to N332. The N332L mutation led to a decrease in the exonuclease activity for representative purine-pyrimidine, and pyrimidine-pyrimidine mismatches at -2 and - 3 positions, respectively. Overall, our findings suggest that conserved polar residues located towards the minor groove may facilitate the detection of position-specific mismatches to enhance the fidelity of DNA synthesis.

Developing competency of nursing students in cardiopulmonary resuscitation using Resuscitation Quality Improvement technology.

OBJECTIVES: This study examined the outcomes of training nursing students in CPR skills using the Resuscitation Quality Improvement (RQI) program. METHODS: Nursing students (n=2,193) in 12 schools across the United States participated in this study. Students performed compressions and bag-masked ventilation on adult and infant manikins using the RQI simulation station without and then with feedback on their performance. RESULTS: With real-time, objective feedback from the RQI simulation station, students' performance of CPR skills improved, and they retained their skills over time. CONCLUSIONS: The RQI program and methodology of feedback is effective for training nursing students to be competent in CPR skills, essential for safe patient care. Nursing and other healthcare professions programs should consider adopting the RQI program for students to develop competency in CPR.

Many-Body Theory Calculations of Positron Scattering and Annihilation in H_{2}, N_{2}, and CH_{4}.

The recently developed ab initio many-body theory of positron molecule binding [22J. Hofierka et al., Many-body theory of positron binding to polyatomic molecules, Nature (London) 606, 688 (2022)NATUAS0028-083610.1038/s41586-022-04703-3] is combined with the shifted pseudostates method [A. R. Swann and G. F. Gribakin, Model-potential calculations of positron binding, scattering, and annihilation for atoms and small molecules using a Gaussian basis, Phys. Rev. A 101, 022702 (2020)PLRAAN2469-992610.1103/PhysRevA.101.022702] to calculate positron scattering and annihilation rates on small molecules, namely H_{2}, N_{2}, and CH_{4}. The important effects of positron-molecule correlations are delineated. The method provides uniformly good results for annihilation rates on all the targets, from the simplest (H_{2}, for which only a sole previous calculation agrees with experiment), to larger targets, where high-quality calculations have not been available.

Age-period-cohort modelling of type 1 diabetes incidence rates among children included in the EURODIAB 25-year follow-up study.

AIMS: Specific patterns in incidence may reveal environmental explanations for type 1 diabetes incidence. We aimed to study type 1 diabetes incidence in European childhood populations to assess whether an increase could be attributed to either period or cohort effects. METHODS: Nineteen EURODIAB centres provided single year incidence data for ages 0-14 in the 25-year period 1989-2013. Case counts and person years were classified by age, period and cohort (APC) in 1-year classes. APC Poisson regression models of rates were fitted using restricted cubic splines for age, period and cohort per centre and sex. Joint models were fitted for all centres and sexes, to find a parsimonious model. RESULTS: A total of 57,487 cases were included. In ten and seven of the 19 centres the APC models showed evidence of nonlinear cohort effects or period effects, respectively, in one or both sexes and indications of sex-specific age effects. Models showed a positive linear increase ranging from approximately 0.6 to 6.6%/year. Centres with low incidence rates showed the highest overall increase. A final joint model showed incidence peak at age 11.6 and 12.6 for girls and boys, respectively, and the rate-ratio was according to sex below 1 in ages 5-12. CONCLUSION: There was reasonable evidence for similar age-specific type 1 diabetes incidence rates across the EURODIAB population and peaks at a younger age for girls than boys. Cohort effects showed nonlinearity but varied between centres and the model did not contribute convincingly to identification of environmental causes of the increase.

TDDFT versus GW/BSE Methods for Prediction of Light Absorption and Emission in a TADF Emitter.

Design concepts for organic light emitting diode (OLED) emitters, which exhibit thermally activated delayed fluorescence (TADF) and thereby achieve quantum yields exceeding 25%, depend on singlet-triplet splitting energies of order kT to allow reverse intersystem crossing at ambient temperatures. Simulation methods for these systems must be able to treat relatively large organic molecules, as well as predict their excited state energies, transition energies, singlet-triplet splittings, and absorption and emission cross sections with reasonable accuracy, in order to prove useful in the design process. Here we compare predictions of TDDFT with M06-2X and ωB97X-D exchange-correlation functionals and a GoWo@HF/BSE method for these quantities in the well-studied DPTZ-DBTO2 TADF emitter molecule. Geometry optimization is performed for ground state (GS) and lowest donor-acceptor charge transfer (CT) state for each functional. Optical absorption and emission cross sections and energies are calculated at these geometries. Relaxation energies are on the order of 0.5 eV, and the importance of obtaining excited state equilibrium geometries in predicting delayed fluorescence is demonstrated. There are clear trends in predictions of GoWo@HF/BSE, and TDDFT/ωB97X-D and M06-2X methods in which the former method favors local exciton (LE) states while the latter favors DA CT states and ωB97X-D makes intermediate predictions. GoWo@HF/BSE suffers from triplet instability for LE states but not CT states relevant for TADF. Shifts in HOMO and LUMO levels on adding a conductor-like polarizable continuum model dielectric background are used to estimate changes in excitation energies on going from the gas phase to a solvated molecule.

Implementation of active injury management (AIM) in youth with acute concussion: A randomized controlled trial.

BACKGROUND: Nearly 2 million youth seek acute medical care following concussion in the U.S. each year. Current standard of care recommends rest for the first 48 h after a concussion. However, research suggests that prolonged rest may lengthen recovery time especially for patients with certain risk profiles. Research indicates that physical activity and behavioral management interventions (sleep, stress management) may enhance recovery. To date, there is limited empirical evidence to inform acute (<72 h) concussion recommendations for physical activity and behavioral management in adolescents. OBJECTIVE: To determine the effectiveness of physical activity and behavioral management for acute concussion in adolescents and young adults, and to evaluate the role of patient characteristics on treatment response. METHODS: This multicenter prospective randomized controlled trial will determine which combination of physical activity and behavioral management is most effective for patients 11-24 years old who present to the emergency department or concussion clinic within 72 h of injury. Participants are randomized into: 1) rest, 2) physical activity, 3) mobile health application (mHealth) behavioral management, or 4) physical activity and mHealth app conditions. Assessments at enrollment, 3-5 days, 14 days, 1 month, and 2 months include: concussion symptoms, balance, vestibular-ocular and cognitive assessments, quality of life, and recovery time. Somatic symptoms and other risk factors are evaluated at enrollment. Compliance with treatment and symptoms are assessed daily using actigraph and daily self-report. The primary study outcome is symptoms at 14 days. CONCLUSION: Prescribed physical activity and behavioral management may improve outcomes in youth following acute concussion.

Newspaper framing of food and beverage corporations' sponsorship of sport: a content analysis.

BACKGROUND: Unhealthy diets are a leading contributor to obesity, disability and death worldwide. One factor cited as contributing to rises in obesity rates is the pervasive and ubiquitous marketing of unhealthy foods and beverages (F&Bs) across a variety of mediums, such as sport sponsorship at both professional and amateur levels. Despite increased academic attention on the detrimental impacts of sport sponsorship within the obesogenic environment, this has not been matched by legislative action. One explanation may be the way that F&B corporations' sport sponsorship is framed within policy debates. Framing is the deliberate ways in which (often contested) issues are presented in communication. This paper examines how sport sponsorship by F&B corporations is framed through media reports. METHODS: This study employed a mixed methods content and framing analysis. First, we conducted a quantitative newsprint content analysis (n = 234). This then informed and directed a thematic framing analysis of a sub-set of articles (n = 54) that specifically associated sport sponsorship by F&B corporations with obesity and childhood obesity. RESULTS: The findings suggest that two competing frames are evident within newspaper coverage: 1) public health and 2) industry. The public health frame rejects the sponsorship of sport by High in Fat Sugar and Salt (HFSS) product corporations in particular, calling for such sponsorship to be restricted or banned. The industry frame characterises sponsorship of sport as a form of corporate social responsibility, positioning industry as good moral actors and part of the solution to childhood and adult obesity. These frames are evident across other Unhealthy Commodity Industries (UCIs) policy debates. However, the prominence of industry actors within the sample is potentially indicative of their discursive power within this space, particularly with their emphasis on the financial maintenance of sport as well as encouraging physical activity, contributing to the lack of regulatory development of sport sponsorship by F&B corporations. CONCLUSIONS: The findings of this study are particularly useful for public health organisations who seek regulatory change, as it may provide further insight into countering industry framing practices, raising the salience of regulation of sport sponsorship and thus increasing the likelihood of regulatory development that seeks to improve population health.

Carbohydrate quantity is more closely associated with glycaemic control than weight in pregnant women with type 1 diabetes: Insights from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT).

BACKGROUND: The present study aimed to explore the relationships between carbohydrate intake, body mass index (BMI) and glycaemic control (HbA1c) in pregnant women with type 1 diabetes mellitus (T1DM) METHODS: Secondary analysis of data was undertaken to assess dietary intake in a cohort of women who participated in a randomised controlled trial (RCT) of antioxidant supplementation to prevent preeclampsia (DAPIT10 ). Study-specific peripheral venous blood samples were obtained for HbA1c at 26 and 34 weeks. Diet was collected using a validated semiquantitative food frequency questionnaire at 26-28 weeks of gestation which assessed dietary intake over 2 weeks. Mean daily average nutrient intakes were analysed using Q Builder nutritional software and SPSS, version 25. RESULTS: Dietary data were available for 547 pregnant women (72% of cohort) aged 29 years (95% confidence interval [CI] = 28.9-29.9) with average diabetes duration 11.8 years (95% confidence interval = 11.1-12.6). Average body mass index (BMI) (<16 weeks of gestation) was 26.7 kg/m2 (95% CI = 26.3 -27, range 18.8-45.6 kg/m2 ); 43% (n = 234) were overweight (BMI = 25.0-29.9 kg/m2 ) and 20% (n = 112) were obese (BMI ≥ 30 kg/m2 ). Differences in HbA1c and carbohydrate quantity and quality were found when adjusted for age and insulin dose. No differences between BMI group were observed for total carbohydrate and glycaemic control; however, differences were noted in fibre and glycaemic index. CONCLUSIONS: Average quantity of dietary carbohydrate influenced HbA1c when adjusted for insulin dose however, BMI had less impact. More research is required on the relationship between carbohydrate consumption and glycaemic control in pregnancy.

The Effect of Multiple Assessments on Delirium Detection: a Pilot Study.

BACKGROUND: Delirium is characterized by fluctuating attention or arousal, with high prevalence in the orthopaedic ward. Our aim was to: 1) establish the prevalence of delirium on an orthopaedic ward, and 2) compare delirium prevalence using a single geriatrician assessment vs. multiple 3D-CAM (3-Minute Diagnostic Interview for Confusion Assessment Method) assessments during the day. We hypothesized that multiple assessments would increase the detection rate due to the fluctuating nature of delirium. METHODS: Comparative study conducted at an academic hospital in Hamilton, Ontario. Participants included patients 65 years and older admitted to the orthopaedic ward (n=55). After a geriatrician made the first assessment of delirium by 3D-CAM on each patient, teams with specialized geriatrics training re-assessed participants up to four times. Delirium rates based on first assessment were compared to cumulative end-of-day rates to determine if detection increased with multiple assessments. RESULTS: The prevalence of delirium was 30.9% (17 participants) using multiple assessments. Of these cases, 13 (76.4%) were detected in the initial geriatrician assessment. In patients with hip fractures, 70.6% (12 of 17) were identified as delirious by multiple assessments. CONCLUSION: As symptoms fluctuate, multiple daily CAM assessments may increase the identification of delirium in orthopaedic inpatients.

Density fitting in periodic systems: Application to TDHF in diamond and oxides.

A robust density fitting method for calculating Coulomb matrix elements over Bloch functions based on the calculation of two- and three-center matrix elements of the Ewald potential is described and implemented in a Gaussian orbital basis in the Exciton code. The method is tested by comparing Coulomb and exchange energies from density fitting to corresponding energies from SCF Hartree-Fock (HF) calculations for diamond, magnesium oxide, and bulk Ne. Density fitting coefficients from the robust method are compared to coefficients from a variational method applied to wave function orbital products in bulk Ne. Four center Coulomb matrix elements from density fitting are applied to time dependent (TDHF) calculations in diamond, magnesium oxide, and anatase and rutile polytypes of titanium dioxide. Shifting virtual states downwards uniformly relative to occupied states and scaling the electron-hole attraction term in the TDHF Hamiltonian by 0.4 yields good agreement with either experiment or Bethe-Salpeter equation calculations. This approach mirrors similar "scissors" adjustments of occupied and virtual states and introduction of a scaled electron-hole attraction term in some time dependent DFT calculations.

Excited state intramolecular proton transfer in hydroxyanthraquinones: Toward predicting fading of organic red colorants in art.

Compositionally similar organic red colorants in the anthraquinone family, whose photodegradation can cause irreversible color and stability changes, have long been used in works of art. Different organic reds, and their multiple chromophores, suffer degradation disparately. Understanding the details of these molecules' degradation therefore provides a window into their behavior in works of art and may assist the development of improved conservation methods. According to one proposed model of photodegradation dynamics, intramolecular proton transfer provides a kinetically favored decay pathway in some photoexcited chromophores, preventing degradation-promoting electron transfer (ET). To further test this model, we measured excited state lifetimes of substituted gas-phase anthraquinones using high-level theory to explain the experimental results. The data show a general structural trend: Anthraquinones with 1,4-OH substitution are long-lived and prone to damaging ET, while excited state intramolecular proton transfers promote efficient quenching for hydroxyanthraquinones that lack this motif.

Clinical utility of ultrasonography-measured visceral adipose tissue depth as a tool in early pregnancy screening for gestational diabetes: a proof-of-concept study.

AIM: To examine, in a proof-of-concept study, the ability of visceral adipose tissue depth and subcutaneous fat depth measured in early pregnancy to predict subsequent gestational diabetes, and to assess the performance of these measures as screening tests for gestational diabetes compared with use of the current UK criteria. METHODS: A total of 100 women in early pregnancy were recruited from a maternity hospital in Belfast, UK. Visceral adipose tissue depth and subcutaneous fat depth were measured, and each participant underwent a 75-g oral glucose tolerance test at 28 weeks' gestation for the diagnosis of gestational diabetes using WHO 2013 criteria. RESULTS: Eighty women completed the study, of whom 15 (19%) developed gestational diabetes. Increasing visceral adipose tissue depth, but not subcutaneous fat depth, was associated with greater gestational diabetes risk after adjusting for confounding factors (odds ratio for a 1-sd rise 2.09, 95% CI 1.06-4.12; P=0.03). Visceral adipose tissue depth ≥4.27 cm had greater sensitivity compared with current National Institute of Health and Care Excellence criteria (87% vs 40%, respectively; P=0.02) and similar specificity (62% vs 74%, respectively; P=0.15) for identifying gestational diabetes. CONCLUSIONS: Ultrasonography-measured visceral adipose tissue in early pregnancy is a potential clinical tool for improving sensitivity of selective screening for gestational diabetes, which, compared with universal oral glucose tolerance testing, is likely to reduce by half the numbers requiring this test. Further larger studies are now required for confirmation, including investigation into impact on clinical outcomes.

Development of a Core Outcome Set for studies evaluating the effects of anaesthesia on perioperative morbidity and mortality following hip fracture surgery.

BACKGROUND: Perioperative studies of patients following hip fracture have large heterogeneity within their reported outcomes. This study aimed to develop a core outcome set for use in perioperative studies comparing the types of anaesthesia for hip fracture surgery. METHODS: The consensus process consisted of a systematic review of the literature, three rounds of a Delphi survey, two consensus webinars, and face-to-face patient meetings. RESULTS: The Delphi participants represented nine stakeholder groups. The numbers of participants completing Rounds 1-3 were 242, 186, and 169, respectively. Seventeen outcomes that met the predefined consensus criteria were considered at two consensus meetings. A final set of 10 core outcomes was agreed: mortality, time from injury to surgery, acute coronary syndrome, hypotension, acute kidney injury, delirium, pneumonia, orthogeriatric input, being out of bed at day 1, and pain. CONCLUSIONS: We generated a consensus-based set of core outcomes recommended for use in all perioperative trials evaluating the effects of anaesthesia for hip fracture surgery. An important next step is developing consensus-based consistency on how they should be measured. CLINICAL TRIAL REGISTRATION: http://www.comet-initiative.org/studies/details/757.

Testing Quantum Electrodynamics in the Lowest Singlet State of Neutral Beryllium-9.

We report spectroscopic results on the 2s2p^{1}P_{1} state in neutral atomic beryllium-9. The absolute frequency for the center of gravity is determined to be 42 565.4501(13) cm^{-1}, a factor of 130 more precise than the previous experimental measurement. The result is in agreement with and a factor of 8 more precise than the current best theoretical estimate of 42 565.441(11) cm^{-1}, which was calculated including the effects of quantum electrodynamics. Because of the large natural linewidth of the transition, the hyperfine constants were not able to be extracted to high precision.

Maternal vitamin D and markers of glycaemia during pregnancy in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome study.

AIMS: To measure total 25-hydroxyvitamin D levels in women in mid-pregnancy who participated in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) observational study, and to investigate the associations between levels of 25-hydroxyvitamin D and markers of gestational diabetes mellitus and lipid biomarkers. METHODS: A total of 1585 pregnant women had serum samples available for measurement. Participants were recruited from the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, at 24-32 weeks' gestation, as part of the HAPO study. 25-hydroxyvitamin D concentrations were measured using liquid chromatography tandem mass spectrometry. Glucose, C-peptide and lipid levels were previously analysed in a central laboratory. Statistical analysis was performed. RESULTS: The median (interquartile range) 25-hydroxyvitamin D concentration during pregnancy was 38.6 (24.1-60.7) nmol/l, with 65.8% of women being vitamin D-deficient (≤50 nmol/l). In regression analysis, the association between maternal 25-hydroxyvitamin D and fasting plasma glucose levels approached significance [regression coefficient -0.017 (95% CI -0.034 to 0.001); P=0.06], and a significant positive association was observed between maternal 25-hydroxyvitamin D and ß-cell function [1.013 (95% CI 1.001 to 1.024); P=0.031]. Maternal 25-hydroxyvitamin D level was positively associated with HDL [0.047 (95% CI 0.021 to 0.073) P≤ 0.001] and total cholesterol [0.085 (95% CI 0.002 to 0.167); P=0.044] in regression analysis. CONCLUSIONS: These results indicate a high prevalence of vitamin D deficiency during pregnancy, which requires identification and treatment; however, only weak associations were observed between 25-hydroxyvitamin D level and markers of glucose and insulin metabolism. This would suggest that these are of doubtful clinical significance.

Calibrating an ultra-low expansion cavity for high precision spectroscopy from 630 THz to 685 THz using molecular tellurium lines.

We report on the calibration of a temperature stabilized ultra-low expansion (ULE) cavity using previously measured molecular tellurium and atomic cesium lines. By means of a dual frequency modulation technique, the frequency dependence of the free spectral range of the ULE cavity is measured and was found to vary by less than 60 Hz over the ∼55 THz range of the calibration. This method of calibration enables the ULE cavity to measure absolute frequencies to better than 1.5 MHz.