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Objective: Educational material on type 1 diabetes (T1D) is limited. An educational application named Sten-O Starter has been implemented for children and adolescents with T1D and their parents; however, its effect on glycemic management is unknown. The objective was therefore to examine the clinical impact of the Sten-O Starter on glycemic management among children and adolescents with T1D. Methods: The levels of glycated hemoglobin (HbA1c) at 0–12 months after diagnosis were compared between two cohorts (the intervention received Sten-O Starter and the control received usual care). A mixed model of repeated measurements adjusted for age, sex, and HbA1c at diagnosis was used. A subgroup analysis of the cohorts was performed in which the time in range, time above range, and time below range (TBR) were compared at 6 months and 12 months after diagnosis using the Wilcoxon rank sum test. Results: 181 children and adolescents were included and all HbA1c measurements from the time of diagnosis to 12-month follow-up: No significant difference (p = 0.35) was found in HbA1c changes between the cohorts. However, the difference in median HbA1c at the 12-month follow-up between the intervention cohort and the control cohort (50 mmol/mol vs. 54 mmol/mol) was borderline significant (p = 0.059). A subgroup analysis of 30 children and adolescents revealed that TBR was significantly different (intervention: 1.2 % vs control: 2.6 %; p = 0.02) at 6 months and at 12 months (intervention: 1 % vs control; 2 %; p = 0.05). Conclusion: The results indicate improved glycemic management among children and adolescents with T1D after use of the Sten-O Starter.

We report a boy with hypercalcemia due to neonatal severe hyperparathyroidism (NSHPT) caused by a compound heterozygous mutation in the calcium sensing receptor (CaSR) managed successfully on a type II calcimimetic drug. The hypercalcemia was temporarily treated by hyperhydration, bisphosphonate and calcium depleted milk. At 29 days of age cinacalcet was introduced. The starting dose was 0.5 mg/kg/day and was subsequently titrated to the point of efficacy (5.2 mg/kg/day) when a persuasive reduction in parathyroid hormone and calcium concentrations was observed. We propose a trial of type II calcimimetics in newborns with NSHPT irrespective of the genetic mutation and advocate that residual functionality of the CaSR predict the drug efficacy.

Groundwater-borne contaminants such as nutrients, dissolved organic carbon (DOC), coloured dissolved organic matter (CDOM) and pesticides can have an impact the biological quality of lakes. The sources of pollutants can, however, be difficult to identify due to high heterogeneity in groundwater flow patterns. This study presents a novel approach for fast hydrological surveys of small groundwater-fed lakes using multiple groundwater-borne tracers. Water samples were collected from the lake and temporary groundwater wells, installed every 50 m within a distance of 5–45 m to the shore, were analysed for tracer concentrations of CDOM, DOC, total dissolved nitrogen (TDN, groundwater only), total nitrogen (TN, lake only), total dissolved phosphorus (TDP, groundwater only), total phosphorus (TP, lake only), δ18O ∕ δ16O isotope ratios and fluorescent dissolved organic matter (FDOM) components derived from parallel factor analysis (PARAFAC). The isolation of groundwater recharge areas was based on δ18O measurements and areas with a high groundwater recharge rate were identified using a microbially influenced FDOM component. Groundwater discharge sites and the fractions of water delivered from the individual sites were isolated with the Community Assembly via Trait Selection model (CATS). The CATS model utilized tracer measurements of TDP, TDN, DOC and CDOM from the groundwater samples and related these to the tracer measurements of TN, TP, DOC and CDOM in the lake. A direct comparison between the lake and the inflowing groundwater was possible as degradation rates of the tracers in the lake were taken into account and related to a range of water retention times (WRTs) of the lake (0.25–3.5 years in 0.25-year increments). These estimations showed that WRTs above 2 years required a higher tracer concentration of inflowing water than found in any of the groundwater wells around the lake. From the estimations of inflowing tracer concentration, the CATS model isolated groundwater discharge sites located mainly in the eastern part of the lake with a single site in the southern part. Observations from the eastern part of the lake revealed an impermeable clay layer that promotes discharge during heavy precipitation events, which would otherwise be difficult to identify using traditional hydrological methods. In comparison to the lake concentrations, high tracer concentrations in the southern part showed that only a smaller fraction of water could originate from this area, thereby confirming the model results. A Euclidean cluster analysis of δ18O isotopes identified recharge sites corresponding to areas adjacent to drainage channels, and a cluster analysis of the microbially influenced FDOM component C4 further identified five sites that showed a tendency towards high groundwater recharge rate. In conclusion, it was found that this methodology can be applied to smaller lakes within a short time frame, providing useful information regarding the WRT of the lake and more importantly the groundwater recharge and discharge sites around the lake. Thus, it is a tool for specific management of the catchment.

Purpose: Phonological awareness and alphabet knowledge are fundamental building blocks for literacy development. We identified preschoolers with persistent delays in these skills and evaluated the efficacy of a supplemental curriculum to remediate deficits in early literacy skills. Method: Using a cluster design, 21 classrooms were randomly assigned to early literacy versus language intervention conditions. Sixty children identified through fall semester assessments of phonological awareness and alphabet knowledge were enrolled in small-group instruction. Teachers completed eLearning modules, used a digital platform to enter data and facilitate data-based decision making, received practice-based coaching, and delivered 12 weekly units of an early literacy curriculum. Comparison teachers delivered similarly administered small-group language instruction. Results: Large effects were evident for letter sounds, phoneme segmentation, first sound, and first sound fluency measures (d= 0.92, 4.77, 1.15, and 1.50, respectively), and nonsignificant, small effects for letter naming and blending measures (d = 0.26 and 0.27). Discussion: This early literacy intervention package had practical benefits, with 90% of experimental group preschoolers exceeding the phonemic awareness benchmark for beginning kindergarten compared to 45% in the comparison group, for example. Providing preschool teachers with tools and support for implementing a tiered approach to early literacy intervention holds promise for producing impressive gains in skills required for children to succeed in later schooling.

ObjectivesTo determine the stance duration and ground reaction forces (GRF) of horses with deep digital flexor (DDF) tendinopathy at the level of the foot and compare the stance duration and GRF to those of clinically sound horses.DesignProspective clinical study.AnimalsSixteen horses (seven horses with bilateral forelimb lameness, four horses with unilateral forelimb lameness, and five horses with no lameness).ProceduresAnalyses of kinetic variables were performed on both forelimbs from sound horses and horses diagnosed with chronic DDF tendinopathy. Stance duration and longitudinal and vertical components of the GRF were determined for the limbs of clinically sound horses and limbs of horses with DDF tendinopathy. Separate Spearman correlation analyses were used to assess potential association within groups (combined left and right forelimbs of clinically sound horses, lamest limbs of horses with DDF tendinopathy, and contralateral limbs of horses with DDF tendinopathy) and with the set of kinetic variables. Analysis of variance on mean ranks of tied values was used to determine differences in kinetic variables between groups (PROC GLIMMIX) using the kinetic values of the clinically sound horses as the reference group.ResultsThere were a total of 11 lame horses. Seven horses had bilateral forelimb lameness and four had unilateral lameness. Of the 11 horses, there were 15 DDF tendinopathies. There were eight dorsal border DDF tendinopathies, five core DDF tendinopathies, and two sagittal/parasagittal splits DDF tendinopathies. The most lame limbs of horses with DDF tendinopathy had significantly smaller values for peak vertical force and time of peak braking force than did forelimbs of clinically sound horses. Also, the most lame limbs of horses with DDF tendinopathy had significantly larger values for the time of peak vertical force than did forelimbs of clinically sound horses.Conclusions and Clinical RelevanceHorses with chronic DDF tendinopathies develop certain alterations of GRF parameters. This information can be used in future studies to determine if particular kinetic variable changes in horses with DDF tendinopathies differ from those of horses with other pathologies within the foot and therefore could be diagnostic.

In this study, the influence of the mesoporous silica (MS) textural properties (surface area, pore diameter, and pore volume) on drug loading capacity (monomolecular loading capacity and pore filling capacity) was investigated theoretically and experimentally using a thermoanalytical method. The loading capacities of three model drugs (celecoxib, cinnarizine, and paracetamol) were determined in five different MS grades of Sylysia® with identical chemical composition, but varying surface area, pore diameter and pore volume. The experimentally determined loading capacities were compared to theoretical loading capacities, calculated based on the surface area and amorphous density of the drugs, and the surface area and pore volume of the MS. The findings of the study showed that the monomolecular loading capacity generally increased with increasing surface area and decreasing pore volume of the MS. However, the MS grade with the highest surface area did not display the highest monomolecular loading capacity for any of the three drugs. This was probably a result of the decreasing pore diameter necessary to accommodate the increasing surface area of the MS i.e., if the pore is smaller than the drug molecule, the drug cannot access the available surface area. For these systems, the amorphous density of the drug and the pore volume of the MS was used to estimate the theoretical pore filling capacity, which was in good agreement with the experimentally determined loading capacity. In conclusion, this study showed that both the pore volume and surface area of the MS will have an influence on the drug loading capacity and that this can be estimated with good accuracy both theoretically and experimentally. Keywords: Mesoporous silica, Loading capacity, Differential scanning calorimetry (DSC), Poorly soluble drugs, Amorphous stability, Surface area, Pore volume, Pore diameter

Major implications on a country's economy, food source, and public health. With recent concern over the highly pathogenic avian influenza outbreaks around the world, government agencies are carefully monitoring and inspecting live bird markets, commercial flocks, and migratory bird populations. However, there remains limited surveillance of non-commercial poultry. Therefore, a cross-sectional study was conducted in backyard poultry flocks using a convenience sampling method across three regions of Maryland from July 2011 to August 2011. The objective of this study was to develop a better understanding of the ecology and epidemiology of avian influenza by investigating the prevalence and seroprevalence in this potentially vulnerable population and by evaluating biosecurity risk factors associated with positive findings. Serum, tracheal, and cloacal swabs were randomly collected from 262 birds among 39 registered premises. Analysis indicated bird and flock seroprevalence as 4.2% (11/262) and 23.1% (9/39), respectively. Based on RT-qPCR analysis, none of the samples were found to be positive for AI RNA and evidence of AI hemagglutinin subtypes H5, H7, or H9 were not detected. Although no statistically significant biosecurity associations were identified (p≤0.05), AI seroprevalence was positively associated with exposure to waterfowl, pest control, and location. AI seropositive flocks exposed to waterfowl were 3.14 times as likely to be AI seropositive than those not exposed (p = 0.15). AI seropositive flocks that did not use pest control were 2.5 times as likely to be AI seropositive compared to those that did and AI seropositive flocks located in the Northern region of Maryland were 2.8 times as likely to be AI seropositive than those that were located elsewhere.

A public plan for eradicating Salmonella in Danish table-egg production was implemented in 1996. During 2002, the poultry industry took over the responsibility of the programme. The proportion of infected layer flocks was reduced from 13.4% in 1998 to 0.4% in 2006. The public-health impact of the plan has been quite marked. In 1997, 55-65% of the 5015 cases of human salmonellosis were estimated to be associated with eggs. In 2006, these figures were reduced to 1658 and 5-7%, respectively. Based on an assessment of the number of human cases attributable to table eggs, we used probabilistic modelling to estimate the avoided societal costs (health care and lost labour), and compared these with the public costs of control. The probable avoided societal costs during 1998-2002 were estimated to be 23.3 million euros (95% CI 16.3-34.9), and the results showed a continuous decreasing cost-benefit ratio reaching well below 1 in 2002. Further reductions in the primary production based on effective surveillance and control are required to ensure continued success. [ABSTRACT FROM AUTHOR]

BACKGROUND: Spontaneous mutations in germ cells increase with male age, but an association between paternal age and congenital malformations is not well established. We conducted a population-based cohort study to estimate this association. METHODS: A study population of couples and their firstborn children were identified in the Danish Fertility Database between 1980 and 1996 (n = 71 937). Diagnoses of congenital malformations in children were obtained by linkage to the nationwide hospital register (19801999). RESULTS: Overall, there were no differences in the prevalence of malformations as a function of paternal age. However, the prevalence of malformations of extremities and syndromes of multiple systems, as well as Downs syndrome, increased with increasing paternal age. For example, in comparison with fathers age 2029 years, adjusted hazard ratio of syndromes of multiple systems was 1.15 [95% confidence interval (CI) 0.811.65] for age 3539 years, 1.33 (95% CI 0.792.25) for age 4044 years, 1.73 (95% CI 0.823.65) for age 4549 years, and 3.20 (95% CI 1.377.48) for age $50 years (test for trend P = 0.01). CONCLUSIONS: Our data suggest that advanced paternal age may be associated with an excess occurrence of some specific malformations. The association could be caused by mutations of the gametes in men induced by biological or environmental factors. [ABSTRACT FROM AUTHOR]

Upconversion of sunlight with energy below the band gap of a solar cell is a promising technique for enhancing the cell efficiency, simply by utilizing a larger part of the solar spectrum. The present topical review addresses this concept and discusses the material properties needed for an efficient upconversion process with focus on both silicon and organic solar cells. To design efficient upconverters, insight into topics such as quantum-optics, nano-optics, numerical modeling, optimization, material fabrication, and material characterization is paramount, and the necessary concepts are introduced throughout the review. Upconversion modeling is done using rate equations, while optical modeling is done by solving Maxwell’s equations using the finite element method. Topology optimization is introduced and used to generate geometries of gold nanoparticles capable of greatly enhancing the upconversion yield. Fabrication and experimental characterization methods are discussed. Some recent results are presented and finally the possibility of designing upconverting materials capable of increasing the short-circuit current in a solar cell is discussed. [ABSTRACT FROM AUTHOR]

Abstract Human glial progenitor cells (hGPCs) exhibit diminished expansion competence with age, as well as after recurrent demyelination. Using RNA-sequencing to compare the gene expression of fetal and adult hGPCs, we identify age-related changes in transcription consistent with the repression of genes enabling mitotic expansion, concurrent with the onset of aging-associated transcriptional programs. Adult hGPCs develop a repressive transcription factor network centered on MYC, and regulated by ZNF274, MAX, IKZF3, and E2F6. Individual over-expression of these factors in iPSC-derived hGPCs lead to a loss of proliferative gene expression and an induction of mitotic senescence, replicating the transcriptional changes incurred during glial aging. miRNA profiling identifies the appearance of an adult-selective miRNA signature, imposing further constraints on the expansion competence of aged GPCs. hGPC aging is thus associated with acquisition of a MYC-repressive environment, suggesting that suppression of these repressors of glial expansion may permit the rejuvenation of aged hGPCs.

Summary: N-methyl-D-aspartate (NMDA)-type ionotropic glutamate receptors have essential roles in neurotransmission and synaptic plasticity. Previously, we identified an evolutionarily conserved protein, NRAP-1, that is required for NMDA receptor (NMDAR) function in C. elegans. Here, we demonstrate that NRAP-1 was sufficient to gate NMDARs and greatly enhanced glutamate-mediated NMDAR gating, thus conferring coincident activation properties to the NMDAR. Intriguingly, vertebrate NMDARs—and chimeric NMDARs where the amino-terminal domain (ATD) of C. elegans NMDARs was replaced by the ATD from vertebrate receptors—were spontaneously active when ectopically expressed in C. elegans neurons. Thus, the ATD is a primary determinant of NRAP-1- and glutamate-mediated gating of NMDARs. We determined the crystal structure of NRAP-1 at 1.9-Å resolution, which revealed two distinct domains positioned around a central low-density lipoprotein receptor class A domain. The NRAP-1 structure, combined with chimeric and mutational analyses, suggests a model where the three NRAP-1 domains work cooperatively to modify the gating of NMDARs.

Background: Intracoronary physiology, particularly fractional flow reserve (FFR), has been used as a guide for revascularization for patients with coronary artery disease (CAD). The optimal treatment in the physiological grey-zone area has been unclear and remains subject to ongoing debate. Methods: We conducted a systematic review of randomized controlled trials and observational studies comparing the prognostic effect of percutaneous coronary revascularization (PCI) and optimal medical therapy (OMT) in patients with CAD. Studies were identified by medical literature databases. The outcomes of interest were major adverse cardiac events (MACE) and its components, death, myocardial infarction (MI), and repeat revascularization. Results: A total of 16 studies with 27,451 patients were included. The pooled analysis demonstrated that PCI was associated with a prognostic advantage over OMT in patients with FFR value ≤0.80 (RR: 0.64, 95 % CI: 0.45–0.90, p 0.80 were shown to benefit more from OMT (RR 1.38, 95 % CI 1.24–1.53, p 0.80, OMT was associated with favorable outcomes over PCI in reducing the risk of MACE. However, among patients with FFR values ≤0.80, revascularization was superior in terms of reducing MACE. The available evidence supports the guideline-recommended use of an FFR cut-off of ≤0.80.

BackgroundPrior suicide attempts are a relatively strong risk factor for future suicide attempts. There is growing interest in using longitudinal electronic health record (EHR) data to derive statistical risk prediction models for future suicide attempts and other suicidal behavior outcomes. However, model performance may be inflated by a largely unrecognized form of “data leakage” during model training: diagnostic codes for suicide attempt outcomes may refer to prior attempts that are also included in the model as predictors. ObjectiveWe aimed to develop an automated rule for determining when documented suicide attempt diagnostic codes identify distinct suicide attempt events. MethodsFrom a large health care system’s EHR, we randomly sampled suicide attempt codes for 300 patients with at least one pair of suicide attempt codes documented at least one but no more than 90 days apart. Supervised chart reviewers assigned the clinical settings (ie, emergency department [ED] versus non-ED), methods of suicide attempt, and intercode interval (number of days). The probability (or positive predictive value) that the second suicide attempt code in a given pair of codes referred to a distinct suicide attempt event from its preceding suicide attempt code was calculated by clinical setting, method, and intercode interval. ResultsOf 1015 code pairs reviewed, 835 (82.3%) were nonindependent (ie, the 2 codes referred to the same suicide attempt event). When the second code in a pair was documented in a clinical setting other than the ED, it represented a distinct suicide attempt 3.3% of the time. The more time elapsed between codes, the more likely the second code in a pair referred to a distinct suicide attempt event from its preceding code. Code pairs in which the second suicide attempt code was assigned in an ED at least 5 days after its preceding suicide attempt code had a positive predictive value of 0.90. ConclusionsEHR-based suicide risk prediction models that include International Classification of Diseases codes for prior suicide attempts as a predictor may be highly susceptible to bias due to data leakage in model training. We derived a simple rule to distinguish codes that reflect new, independent suicide attempts: suicide attempt codes documented in an ED setting at least 5 days after a preceding suicide attempt code can be confidently treated as new events in EHR-based suicide risk prediction models. This rule has the potential to minimize upward bias in model performance when prior suicide attempts are included as predictors in EHR-based suicide risk prediction models.

Exposure to bioaerosols in occupational settings is associated with a range of adverse health effects. The aim of this study was to investigate the exposure levels to dust and endotoxin of people working in two cucumber nurseries and two tomato nurseries. Exposure was measured for greenhouse workers (n = 70) mainly working on harvesting cucumbers and tomatoes and clearing the plants after the harvest season. The people were exposed to between 0.2 and 15 mg inhalable dust m−3 (median = 1.6 mg m−3) and between 0.5 and 400 ng inhalable endotoxin m−3 (median = 32 ng m−3). The exposure to ‘total dust’ and endotoxin measured by stationary samplers (n = 30) in the greenhouses was low. Endotoxin was present in relatively high concentrations on cucumber leaves compared with leaves on pot plants. The Danish occupational exposure limit (OEL) for total organic dust is 3 mg m−3 and 36% and 17% of the cucumber and tomato workers, respectively, were exposed to >3.0 mg inhalable dust m−3. There is no OEL for endotoxin, but ‘no effect levels’ at ∼15 ng m−3 have been found. The majority of subjects (65%) were exposed to >15 ng m−3. Significantly higher exposure was found for employees in cucumber nurseries than for employees in tomato nurseries. Clearing tomato plants after the harvest season caused a higher exposure to endotoxin than tomato harvesting. In conclusion, people working in cucumber and tomato nurseries were often exposed to high levels of inhalable dust and endotoxin. Cucumber harvest workers were exposed to significantly more dust and endotoxin than tomato harvest workers. The dust and endotoxin aerosolized during the working processes were only transported to other areas in the greenhouses to a very low degree. Cucumber and tomato leaves were identified as endotoxin reservoirs. [ABSTRACT FROM AUTHOR]

For studies of the biological effects of bioaerosols, large samples are necessary. To be able to sample enough material and to cover the variations in aerosol content during and between working days, a long sampling time is necessary. Recently, a high-volume transportable electrostatic field sampler for collection of fine particles has been described. The aim of this study was to investigate whether this sampler can be used for collection of high amounts of authentic bioaerosols that can subsequently be used for biological analysis. The investigation was carried out at a biofuel plant in a straw storage room and in a boiler room over two seasons. The sampled dust was quantified in terms of mass and characterized regarding microbial components and compared with dust sampled by Gravikon and GSP samplers. For the electrostatic field sampler, a prefilter was used to remove large objects. The prefilter was characterized for particle penetration and this testing indicated that the prefilter did not remove particles up to 10 μm, and therefore respirable dust was sampled by the electrostatic field sampler. Using the electrostatic field sampler in the straw storage and in the boiler room, 330 and 315 mg dust (net recovery of the lyophilized dust) was sampled during a period of 7 days, respectively. The sampling rates of the electrostatic field samplers were between 1.34 and 1.96 mg dust per hour, the value for the Gravikon was between 0.083 and 0.108 mg dust per hour and the values for the GSP samplers were between 0.0031 and 0.032 mg dust per hour. The standard deviations of replica samplings and the following microbial analysis using the electrostatic field sampler and GSP samplers were at the same levels. The exposure to dust in the straw storage was 7.7 mg m−3 when measured by the electrostatic field sampler and 11.8 mg m−3 when measured by the GSP inhalable dust sampler. The quantity (amount per mg dust) of total fungi, Aspergillus fumigatus, total bacteria, endotoxin and mesophilic actinomycetes sampled by the electrostatic field samplers and the Gravikon samplers varied within the same season by a factor smaller than four. The quantities of some microbial components were higher in the dust collected with all samplers in March than in August. In conclusion, by using the electrostatic field sampler, it was possible to sample replicas of large authentic aerosol samples that can be used, e.g. biological analysis. (Sharma AK et al., 2007a). [ABSTRACT FROM AUTHOR]

Abstract Clinical risk prediction models powered by electronic health records (EHRs) are becoming increasingly widespread in clinical practice. With suicide-related mortality rates rising in recent years, it is becoming increasingly urgent to understand, predict, and prevent suicidal behavior. Here, we compare the predictive value of structured and unstructured EHR data for predicting suicide risk. We find that Naive Bayes Classifier (NBC) and Random Forest (RF) models trained on structured EHR data perform better than those based on unstructured EHR data. An NBC model trained on both structured and unstructured data yields similar performance (AUC = 0.743) to an NBC model trained on structured data alone (0.742, p = 0.668), while an RF model trained on both data types yields significantly better results (AUC = 0.903) than an RF model trained on structured data alone (0.887, p

Background: Current treatments for progressive neurodegenerative disorders characterized by cognitive impairment either have limited efficacy or are lacking altogether. SDI-118 is a small molecule which modulates the activity of synaptic vesicle glycoprotein 2A (SV2A) in the brain and shows cognitive enhancing effects in a range of animal models of cognitive deficit.Methods: This first-in-human study evaluated safety, tolerability, and pharmacokinetics/pharmacodynamics of SDI-118 in single ascending oral doses up to 80 mg administered to 32 healthy male subjects. Brain target occupancy was measured in eight subjects using positron emission tomography with PET-ligand [11C]-UCB-J. Food effect was assessed in seven subjects. Mood state was regularly evaluated using standardized questionnaires, and resting state fMRI data were analyzed as exploratory objectives.Key Results: At all doses tested, SDI-118 was well tolerated and appeared safe. Adverse events were mainly dizziness, hypersomnia, and somnolence. All were mild in intensity and increased in frequency with increasing administered dose. No dose-limiting adverse reactions were observed at any dose. SDI-118 displayed a linear pharmacokinetic profile with no significant food effect. Brain penetration and target engagement were demonstrated by a dose-proportional SV2A occupancy.Conclusion: Single oral doses of SDI-118 up to 80 mg were very well tolerated in healthy male subjects. Dose-proportional SV2A occupancy in the brain was demonstrated with brain imaging. Adverse effects in humans mainly occurred in higher dose ranges, with high occupancy levels, and were all mild and self-limiting. These data support further clinical exploration of the compound in patients with cognitive disorders.Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT05486195

Objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared 5‐year adverse event (AE) incidence rates (IRs) between patients initiating tofacitinib and those initiating new biological disease‐modifying antirheumatic drugs (bDMARDs) within the United States (US) Corrona RA registry. Methods IRs (number of first events/100 patient‐years) of major adverse cardiovascular events (MACE), serious infection events (SIEs), herpes zoster (HZ), malignancies, and death were estimated among tofacitinib and bDMARD initiators, regardless of dose/schedule, between November 6, 2012 (US Food and Drug Administration tofacitinib approval), and July 31, 2018 (follow‐up through January 31, 2019). Propensity score (PS) methods were used to control for nonrandom prescribing practices. Hazard ratios (HRs) were calculated to compare rates using multivariable‐adjusted Cox regression. Different risk windows were used for acute (MACE, SIEs, HZ, and venous thromboembolic events [VTEs]) and long‐term (malignancy and death) events. VTEs were assessed descriptively. Results For MACE, SIEs, and HZ, 1999 (3152.1 patient‐years) and 8358 (12 869.4 years) tofacitinib and bDMARD initiators were included, respectively; for malignancy/death, 1999 (4505.6 patient‐years) and 6354 (16 670.8 patient‐years) initiators were included, respectively. AE rates were similar across cohorts, except for HZ, which was significantly higher with tofacitinib versus bDMARDs (PS‐trimmed adjusted HR 2.32; 95% confidence interval [CI] 1.43‐3.75). There were 45 (zero serious) and 88 (five serious) HZ events with tofacitinib and bDMARDs, respectively. Sensitivity analyses demonstrated similar results. VTE IRs (95% CI) were 0.29 (0.13‐0.54) and 0.33 (0.24‐0.45) for tofacitinib and bDMARDs, respectively. Conclusion In this registry analysis, both cohorts had similar MACE, SIE, malignancy, death, and VTE rates; HZ rates were higher for tofacitinib initaitors than for bDMARD initiators.

BackgroundInterest in developing machine learning models that use electronic health record data to predict patients’ risk of suicidal behavior has recently proliferated. However, whether and how such models might be implemented and useful in clinical practice remain unknown. To ultimately make automated suicide risk–prediction models useful in practice, and thus better prevent patient suicides, it is critical to partner with key stakeholders, including the frontline providers who will be using such tools, at each stage of the implementation process. ObjectiveThe aim of this focus group study is to inform ongoing and future efforts to deploy suicide risk–prediction models in clinical practice. The specific goals are to better understand hospital providers’ current practices for assessing and managing suicide risk; determine providers’ perspectives on using automated suicide risk–prediction models in practice; and identify barriers, facilitators, recommendations, and factors to consider. MethodsWe conducted 10 two-hour focus groups with a total of 40 providers from psychiatry, internal medicine and primary care, emergency medicine, and obstetrics and gynecology departments within an urban academic medical center. Audio recordings of open-ended group discussions were transcribed and coded for relevant and recurrent themes by 2 independent study staff members. All coded text was reviewed and discrepancies were resolved in consensus meetings with doctoral-level staff. ResultsAlthough most providers reported using standardized suicide risk assessment tools in their clinical practices, existing tools were commonly described as unhelpful and providers indicated dissatisfaction with current suicide risk assessment methods. Overall, providers’ general attitudes toward the practical use of automated suicide risk–prediction models and corresponding clinical decision support tools were positive. Providers were especially interested in the potential to identify high-risk patients who might be missed by traditional screening methods. Some expressed skepticism about the potential usefulness of these models in routine care; specific barriers included concerns about liability, alert fatigue, and increased demand on the health care system. Key facilitators included presenting specific patient-level features contributing to risk scores, emphasizing changes in risk over time, and developing systematic clinical workflows and provider training. Participants also recommended considering risk-prediction windows, timing of alerts, who will have access to model predictions, and variability across treatment settings. ConclusionsProviders were dissatisfied with current suicide risk assessment methods and were open to the use of a machine learning–based risk-prediction system to inform clinical decision-making. They also raised multiple concerns about potential barriers to the usefulness of this approach and suggested several possible facilitators. Future efforts in this area will benefit from incorporating systematic qualitative feedback from providers, patients, administrators, and payers on the use of these new approaches in routine care, especially given the complex, sensitive, and unfortunately still stigmatized nature of suicide risk.

Background and purpose — Several studies suggest a global increase of centenarians during the 21st century. We describe temporal trends of hip fracture incidence and mortality in this group and compare these patients with a group of younger hip fracture patients with regards to comorbidities and mortality. Patients and methods — The full study population included all hip fractures that occurred in Denmark (n = 154,047) between 1996 and 2012. Patients aged 100 or above were identified (n = 507) and hip fracture patients between the ages of 70 to 99 years (n = 124,007) were used for comparison. Data were accessed from national registries. Trends in incidence over time were analyzed using a log-linear regression model, mortality was analyzed using the Kaplan–Meier estimator and trends in mortality over time were analyzed using a log-binomial regression model to obtain relative risk estimates. Results and interpretation — The centenarian patients had fewer comorbidities than the younger comparison group, but mortality was higher at all timepoints. There was no statistically significant change in mortality over time but the incidence of hip fracture among centenarians decreased during the same time period. Our findings describe the characteristics of an emerging group of hip fracture patients and could be of use in the planning of healthcare in the years to come.

Background and purpose — While development in hip fracture incidence and mortality is well examined, none has yet looked at the temporal trends regarding prevalence of co-morbidities. Therefore we investigated changes in incidence of first hip fracture, co-morbidity prevalence, 30 day- and 1-year mortality in hip fracture patients in the Danish population during the period 1999 to 2012. Patients and methods — Patients >18 years admitted with a fractured hip in Denmark between 1996 and 2012 were identified with data for the period 1999–2012 being analyzed regarding prevalence of co-morbidities, incidence, and mortality. Results — 122,923 patients were identified. Incidence in the whole population declined but sex-specific analysis showed no changes for men. For the whole study population, 30-day and 1-year mortality remained unchanged. Age at time of first hip fracture also remained unchanged. Of the included co-morbidities a decrease in prevalence of malignancy and dementia in women was found while there was an increase in the prevalence of all remaining co-morbidities, except hemi- or paraplegia for both sexes, rheumatic diseases for women, and for men diabetes with complications, myocardial infarction, AIDS/HIV, and malignancy. Interpretation — While hip fracture incidence declined for women it was unchanged for men; likewise, 30-day and 1-year mortality rates together with age at first fracture remained unchanged. When these results are compared with the relatively large increase in the prevalence of co-morbidities, it does not seem likely that the increased disease burden is affecting either the incidence or the mortality.

IntroductionPrecipitating factors that contribute to the severity of exertional heat stroke (EHS) are unclear. The purpose of this study was to determine the effect of prior illness (PI) on EHS severity.MethodsWe performed a retrospective clinical record review of 179 documented cases of EHS at the Marine Corps Base in Quantico, Virginia.ResultsApproximately 30% of EHS cases had a medically documented PI. Anthropometrics (height, weight, body mass index) and commonly associated risk factors for EHS (age, number of days in training, wet bulb globe temperature, sleep patterns) did not differ between PI and no illness (NI) groups. PI patients presented with higher maximal rectal core temperatures (40.6 ± 1.0°C vs. 40.3 ± 1.2°C; P = 0.0419), and elevated pulse rates (118.1 ± 16.7 bpm vs. 110.5 ± 24.2 bpm; P = 0.0397). At the point of care, biomarker values were similar between PI and NI groups, with the exception of a trend toward elevated monocytes in those with PI (7.9 ± 2.9% vs 6.7± 2.7%; P = 0.0521). Rate and duration of cooling were similar between PI and NI patients.ConclusionThis study indicates that PI has a minimal effect on the patient presentation, severity and treatment outcome of EHS. The results of this study have important implications for military, civilian, and occupational populations who are at risk for EHS.

Much work in physics education research (PER) characterizes faculty teaching practice in terms of whether faculty use specific named PER-based teaching methods, either with fidelity or with adaptation; we call this research paradigm the “teaching-method-centered paradigm.” However, most faculty do not frame their teaching in terms of which particular named methods they use, but rather in terms of their own ideas and values, suggesting that the teaching-method-centered paradigm misses key features of faculty teaching. These key features include the productive ideas that faculty have about student learning and faculty agency around teaching. We present three case studies of faculty talking about their teaching, and analyze them in terms of two theoretical frameworks: a framework of teaching principles (How Learning Works) and a framework of faculty agency (self-determination theory). We show that these frameworks well characterize key features of faculty teaching practices and agency, and can be combined in a new paradigm for modeling faculty teaching which we call an “asset-based agentic paradigm.” We therefore encourage physics education researchers to move beyond the teaching-method-centered paradigm and think about faculty teaching using an asset-based agentic paradigm.

The era of ‘big data’ studies and computational social science has recently given rise to a number of realignments within and beyond the social sciences, where otherwise distinct data formats – digital, numerical, ethnographic, visual, etc. – rub off and emerge from one another in new ways. This article chronicles the collaboration between a team of anthropologists and sociologists, who worked together for one week in an experimental attempt to combine ‘big’ transactional and ‘small’ ethnographic data formats. Our collaboration is part of a larger cross-disciplinary project carried out at the Danish Technical University (DTU), where high-resolution transactional data from smartphones allows for recordings of social networks amongst a freshman class (N = 800). With a parallel deployment of ethnographic fieldwork among the DTU students, this research set-up raises a number of questions concerning how to assemble disparate ‘data-worlds’ and to what epistemological and political effects? To address these questions, a specific social event – a lively student party – was singled out from the broader DTU dataset. Our experimental collaboration used recordings of Bluetooth signals between students’ phones to visualize the ebb and flow of social intensities at the DTU party, juxtaposing these with ethnographic field-notes on shifting party atmospheres. Tracing and reflecting on the process of combining heterogeneous data, the article offers a concrete case of how a ‘stitching together’ of digital and ethnographic data-worlds might take place.

[b]Introduction.[/b] It is well known that exposure to organic dust can cause adverse respiratory effect. The pathogen-associated molecular patterns (PAMPS) in the organic dust, such as endotoxin from Gram-negative bacteria cell wall and fungal components, can trigger the release of cytokine (e.g. Interleukin 1β (IL-1β)) and chemokine (e.g. Interleukin 8 (IL-8)) from the immune cells in the airways. [b]Objective.[/b] To evaluate the potential inflammatory effects of organic dust exposure in energy plants in Denmark. [b]Materials and methods[/b]. Nasal lavage (NAL) and exhaled breath condensate (EBC) were sampled at Monday morning (referred to as before work) and again at Thursday afternoon (referred to as after work). NAL IL-8, EBC pH, IL-1β concentration were measured. Personal exposure to endotoxin and dust was calculated from time spent on different tasks and measured average work area exposures. [b]Results.[/b] Before work, workers from biofuel plants had a higher IL-1β and IL-8 concentration compared to conventional fuel plants (control group). Specifically, the IL-1β level of moderately and most exposed group, and IL-8 level of the least exposed group were higher compared to the control group. The changes of IL-1β, pH and IL-8 during a work week were not significant. Workers with rhinitis had a lower percentage change of IL-8 compared to healthy workers. [b]Conclusions[/b]. An increased level of EBC IL-1β in biofuel energy plant workers before work indicated a chronic or sub-chronic inflammation. The percentage change of IL-8 was lower in workers with rhinitis compared to healthy workers.

Introduction: Previous smaller studies suggest that anemia is a risk factor for mortality in patients with hip fracture. The purpose of this investigation was to assess the correlation between hemoglobin at admission with 30-day mortality following a hip fracture in a large-scale study. Patients and Methods: From January 1996 to December 2012, all patients with hip fracture (>60 years of age) admitted to Bispebjerg Hospital, Copenhagen, were identified from a local hip fracture database. We excluded conservatively treated patients and patients who died preoperatively. Results: Seven thousand four hundred twenty-one consecutive patients with hip fracture were identified. Of those 7319 had a hemoglobin measurement on admission and were thus eligible for further analysis. Mean hemoglobin for patients alive at 30 days was 7.6 (standard deviation [SD]: 1.0) and for deceased patients 7.4 (SD: 1.1), P < .0001. Mean age was 82.6 years (SD: 8.5), and 76.5% of the population were female (N females = 5600). The 30-day mortality decreases for every increase in hemoglobin of 1.0 mmol/L in a univariate analysis ( P < .0001). The hazard ratio (HR) with 95% confidence interval (CI) for 30-day mortality in patients with anemia (

This study investigated how visual attention differed between those who correctly versus incorrectly answered introductory physics problems. We recorded eye movements of 24 individuals on six different conceptual physics problems where the necessary information to solve the problem was contained in a diagram. The problems also contained areas consistent with a novicelike response and areas of high perceptual salience. Participants ranged from those who had only taken one high school physics course to those who had completed a Physics Ph.D. We found that participants who answered correctly spent a higher percentage of time looking at the relevant areas of the diagram, and those who answered incorrectly spent a higher percentage of time looking in areas of the diagram consistent with a novicelike answer. Thus, when solving physics problems, top-down processing plays a key role in guiding visual selective attention either to thematically relevant areas or novicelike areas depending on the accuracy of a student’s physics knowledge. This result has implications for the use of visual cues to redirect individuals’ attention to relevant portions of the diagrams and may potentially influence the way they reason about these problems.

BackgroundMetabolic engineering is an attractive approach in order to improve the microbial production of drugs. Triterpenes is a chemically diverse class of compounds and many among them are of interest from a human health perspective. A systematic experimental or computational survey of all feasible gene modifications to determine the genotype yielding the optimal triterpene production phenotype is a laborious and time-consuming process.Methodology/principal findingsBased on the recent genome-wide sequencing of Saccharomyces cerevisiae CEN.PK 113-7D and its phenotypic differences with the S288C strain, we implemented a strategy for the construction of a β-amyrin production platform. The genes Erg8, Erg9 and HFA1 contained non-silent SNPs that were computationally analyzed to evaluate the changes that cause in the respective protein structures. Subsequently, Erg8, Erg9 and HFA1 were correlated with the increased levels of ergosterol and fatty acids in CEN.PK 113-7D and single, double, and triple gene over-expression strains were constructed.ConclusionsThe six out of seven gene over-expression constructs had a considerable impact on both ergosterol and β-amyrin production. In the case of β-amyrin formation the triple over-expression construct exhibited a nearly 500% increase over the control strain making our metabolic engineering strategy the most successful design of triterpene microbial producers.

This study investigated how visual attention differed between those who correctly versus incorrectly answered introductory physics problems. We recorded eye movements of 24 individuals on six different conceptual physics problems where the necessary information to solve the problem was contained in a diagram. The problems also contained areas consistent with a novicelike response and areas of high perceptual salience. Participants ranged from those who had only taken one high school physics course to those who had completed a Physics Ph.D. We found that participants who answered correctly spent a higher percentage of time looking at the relevant areas of the diagram, and those who answered incorrectly spent a higher percentage of time looking in areas of the diagram consistent with a novicelike answer. Thus, when solving physics problems, top-down processing plays a key role in guiding visual selective attention either to thematically relevant areas or novicelike areas depending on the accuracy of a student’s physics knowledge. This result has implications for the use of visual cues to redirect individuals’ attention to relevant portions of the diagrams and may potentially influence the way they reason about these problems.