N-Terminal Modification of Gly-His-Tagged Proteins with Azidogluconolactone.

Site-specific protein modifications are vital for biopharmaceutical drug development. Gluconoylation is a non-enzymatic, post-translational modification of N-terminal HisTags. We report high-yield, site-selective in vitro α-aminoacylation of peptides, glycoproteins, antibodies, and virus-like particles (VLPs) with azidogluconolactone at pH 7.5 in 1 h. Conjugates slowly hydrolyse, but diol-masking with borate esters inhibits reversibility. In an example, we multimerise azidogluconoylated SARS-CoV-2 receptor-binding domain (RBD) onto VLPs via click-chemistry, to give a COVID-19 vaccine. Compared to yeast antigen, HEK-derived RBD was immunologically superior, likely due to observed differences in glycosylation. We show the benefits of ordered over randomly oriented multimeric antigen display, by demonstrating single-shot seroconversion and best virus-neutralizing antibodies. Azidogluconoylation is simple, fast and robust chemistry, and should accelerate research and development.

Childhood obesity and dental caries: an ecological investigation of the shape and moderators of the association.

BACKGROUND: Despite sharing a common risk factor in dietary sugars, the association between obesity and dental caries remains unclear. We investigated the association between obesity and dental caries in young children in England in an ecological study. METHODS: We analysed data from 326 lower tier English local authorities. Data on obesity and dental caries were retrieved from 2014/15 to 2016/17 National Child Measurement Programme and 2016/17 National Dental Epidemiology Programme. We used fractional polynomial models to explore the shape of the association between obesity and dental caries. We also examined the modifying effect of deprivation, lone parenthood, ethnicity, and fluoridation. RESULTS: Best fitting second order fractional polynomial models did not provide better fit than the linear models for the association between obesity and prevalence and severity of dental caries; therefore, the linear model was found suitable. Despite significant association, after adjusting for the effect of deprivation, obesity was neither associated with prevalence (coefficient = 0.2, 95% CI - 0.71, 0.75), nor with severity (coefficient = 0.001, 95% CI - 0.03, 0.03) of dental caries. In fully adjusted models, the proportion of white ethnicity and being in fluoridated areas were associated with a decrease in dental caries. The association between obesity and dental caries was moderated by the effect of deprivation, white ethnicity, and lone parenthood. CONCLUSIONS: The association between obesity and dental caries was linear and moderated by some demographic factors. Consequently, interventions that reduce obesity and dental caries may have a greater impact on specific groups of the population.

Leukemia aggressiveness is driven by chromatin remodeling and expression changes of core regulators.

Molecular mechanisms driving clonal aggressiveness in leukemia are not fully understood. We tracked and analyzed two mouse MLL-rearranged leukemic clones independently evolving towards higher aggressiveness. More aggressive subclones lost their growth differential ex vivo but restored it upon secondary transplantation, suggesting molecular memory of aggressiveness. Development of aggressiveness was associated with clone-specific gradual modulation of chromatin states and expression levels across the genome, with a surprising preferential trend of reversing the earlier changes between normal and leukemic progenitors. To focus on the core aggressiveness program, we identified genes with consistent changes of expression and chromatin marks that were maintained in vivo and ex vivo in both clones. Overexpressing selected core genes (Smad1 as aggressiveness driver, Irx5 and Plag1 as suppressors) affected leukemic progenitor growth in the predicted way and had convergent downstream effects on central transcription factors and repressive epigenetic modifiers, suggesting a broader regulatory network of leukemic aggressiveness.

Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer.

Activating innate immunity in cancer cells through cytoplasmic nucleic acid sensing pathways, a phenomenon known as "viral mimicry," has emerged as an effective strategy to convert immunologically "cold" tumors into "hot." Through a curated CRISPR-based screen of RNA helicases, we identified DExD/H-box helicase 9 (DHX9) as a potent repressor of double-stranded RNA (dsRNA) in small cell lung cancers (SCLC). Depletion of DHX9 induced accumulation of cytoplasmic dsRNA and triggered tumor-intrinsic innate immunity. Intriguingly, ablating DHX9 also induced aberrant accumulation of R-loops, which resulted in an increase of DNA damage-derived cytoplasmic DNA and replication stress in SCLCs. In vivo, DHX9 deletion promoted a decrease in tumor growth while inducing a more immunogenic tumor microenvironment, invigorating responsiveness to immune-checkpoint blockade. These findings suggest that DHX9 is a crucial repressor of tumor-intrinsic innate immunity and replication stress, representing a promising target for SCLC and other "cold" tumors in which genomic instability contributes to pathology. SIGNIFICANCE: One promising strategy to trigger an immune response within tumors and enhance immunotherapy efficacy is by inducing endogenous "virus-mimetic" nucleic acid accumulation. Here, we identify DHX9 as a viral-mimicry-inducing factor involved in the suppression of double-stranded RNAs and R-loops and propose DHX9 as a novel target to enhance antitumor immunity. See related commentary by Chiappinelli, p. 389. This article is featured in Selected Articles from This Issue, p. 384.

Area-level inequalities in the provision of NHS orthodontic care in England from 2016 to 2019.

Objective To investigate geographic inequalities in the provision of NHS orthodontic care in England at the area level.Methods NHS dental activity data were analysed for the three financial years April 2016 to March 2019. The measures used were units of dental activity (UDA), units of orthodontic activity (UOA) and commencement of orthodontic treatment. Two orthodontic activity indices were created to assess relative volumes of care. Deprivation was measured using the index of multiple deprivations. Slope and relative inequality indices were used to assess inequality.Results Nearly 12.4 million UOA and 572,987 courses of treatment in England were reported under NHS arrangements in the three years studied. There were significant variations in the rates of UOA (0-716) and UDA (148-918) provided per 100 children (0-17 years) at the local authority level. The variation was not associated with deprivation at the local authority level.Conclusions There were significant disparities in the provision of NHS orthodontic treatment at the local authority level, but this was not associated with area-level measures of deprivation. Inequality in the uptake of orthodontic care may not be due to area-level disparities in service provision.

Fronto-central resting-state 15-29Hz transient beta events change with therapeutic transcranial magnetic stimulation for posttraumatic stress disorder and major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD) and shows promise for posttraumatic stress disorder (PTSD), yet effectiveness varies. Electroencephalography (EEG) can identify rTMS-associated brain changes. EEG oscillations are often examined using averaging approaches that mask finer time-scale dynamics. Recent advances show some brain oscillations emerge as transient increases in power, a phenomenon termed "Spectral Events," and that event characteristics correspond with cognitive functions. We applied Spectral Event analyses to identify potential EEG biomarkers of effective rTMS treatment. Resting 8-electrode EEG was collected from 23 patients with MDD and PTSD before and after 5Hz rTMS targeting the left dorsolateral prefrontal cortex. Using an open-source toolbox ( https://github.com/jonescompneurolab/SpectralEvents ), we quantified event features and tested for treatment associated changes. Spectral Events in delta/theta (1-6 Hz), alpha (7-14 Hz), and beta (15-29 Hz) bands occurred in all patients. rTMS-induced improvement in comorbid MDD PTSD were associated with pre-to post-treatment changes in fronto-central electrode beta event features, including frontal beta event frequency spans and durations, and central beta event maxima power. Furthermore, frontal pre-treatment beta event duration correlated negatively with MDD symptom improvement. Beta events may provide new biomarkers of clinical response and advance the understanding of rTMS.

App-based oral health promotion interventions on modifiable risk factors associated with early childhood caries: A systematic review.

Background: Early childhood caries (ECC) is a preventable chronic disease. Parents' knowledge and attitudes toward oral healthcare have been associated with higher caries experience in their children. Mobile apps within the context of mHealth interventions are a potential tool for raising awareness and informing parents about their children's oral health. Objectives: The aim of this systematic review was to examine the effectiveness of mobile health apps, targeted at parents and caregivers, for the prevention of ECC. Data sources: A systematic search was carried out in five scientific databases; Embase, CINAHL, MEDLINE, PsycINFO and Web of Science. Study selection and data extraction: Original studies, delivering oral health interventions to parents of children <6 years via smartphones, were included. Both quantitative and qualitative findings from the included studies were extracted. Synthesis: A convergent segregated approach was used to integrate the quantitative and qualitative evidence, followed by side-by-side display and narrative synthesis. Results: Out of 5,953 retrieved articles, five met the inclusion criteria and were included in the review. Three articles reported quantitative findings, while two reported both quantitative and qualitative findings. Four studies reported that a mobile app can be an effective tool to improve the oral health knowledge of parents/caregivers, aiding them in incorporating good oral health habits into their children's daily routines. Conclusion: This review demonstrated that oral health promotion programs delivered through mobile apps to parents could be effective in improving child oral health awareness among parents. There is a need for more high-quality studies with a large number of participants to find out which features of mHealth interventions with parents could effectively be employed to reduce the prevalence of ECC. Further studies and apps should be developed based on evidence-based behaviour change techniques and incorporate features such as gamification to increase the effectiveness and engagement of the target population. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?], identifier [CRD42021268331].

Fronto-central resting-state 15-29 Hz transient beta events change with therapeutic transcranial magnetic stimulation for posttraumatic stress disorder and major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD) and shows promise for posttraumatic stress disorder (PTSD), yet effectiveness varies. Electroencephalography (EEG) can identify rTMS-associated brain changes. EEG oscillations are often examined using averaging approaches that mask finer time-scale dynamics. Recent advances show some brain oscillations emerge as transient increases in power, a phenomenon termed "Spectral Events," and that event characteristics correspond with cognitive functions. We applied Spectral Event analyses to identify potential EEG biomarkers of effective rTMS treatment. Resting 8-electrode EEG was collected from 23 patients with MDD and PTSD before and after 5 Hz rTMS targeting the left dorsolateral prefrontal cortex. Using an open-source toolbox ( https://github.com/jonescompneurolab/SpectralEvents ), we quantified event features and tested for treatment associated changes. Spectral Events in delta/theta (1-6 Hz), alpha (7-14 Hz), and beta (15-29 Hz) bands occurred in all patients. rTMS-induced improvement in comorbid MDD PTSD were associated with pre- to post-treatment changes in fronto-central electrode beta event features, including frontal beta event frequency spans and durations, and central beta event maxima power. Furthermore, frontal pre-treatment beta event duration correlated negatively with MDD symptom improvement. Beta events may provide new biomarkers of clinical response and advance the understanding of rTMS.

Effect of modifiable risk factors in Parkinson's disease: A case-control study looking at common dietary factors, toxicants, and anti-inflammatory medications.

OBJECTIVE: To investigate how common modifiable exposures, including dietary factors, select toxicants, and anti-inflammatory medications, may affect Parkinson's disease. METHODS: Using surveys, a case-control study was conducted at a medical center, comparing Parkinson's disease patients (N = 149) and healthy controls (N = 105). Subjects reported exposure to red meats, vegetables, alcohol, tobacco, anti-inflammatory medications, and pesticides. The relationship between exposures and Parkinson's disease diagnosis was analyzed by logistic regression to generate odds ratio and 95% confidence interval. RESULTS: Consuming red meat "sometimes" or "always" was positively associated with Parkinson's disease as compared to eating red meats "rarely" or "never"; (odds ratio = 2.15, 95% confidence interval = 1.06, 4.39; p = 0.03) and (odds ratio = 4.47, 95% confidence interval = 1.67, 11.94; p = 0.003), respectively. Exposure to pesticides showed a positive association with Parkinson's disease (odds ratio = 2.84, 95% confidence interval = 1.34, 6.00; p = 0.007). "Always" use of aspirin was inversely associated with Parkinson's disease (odds ratio = 0.32, 95% confidence interval = 0.14, 0.70; p = 0.004). "Ever" having used anti-histamines was inversely associated with Parkinson's disease (odds ratio = 0.37, 95% confidence interval = 0.17, 0.81; p = 0.01). DISCUSSION: Our study suggests that there are modifiable external factors that are associated with Parkinson's disease. The present study can thus assist clinicians, policy makers, and people living with Parkinson's disease in improving the experience and management of Parkinson's disease.

The "Neglected" Relationship Between Child Maltreatment and Oral Health? An International Scoping Review of Research.

Globally, the oral health needs of children who have, or are suspected of having, experienced abuse or neglect has become a focus of concern. It is thus valuable and timely to map the contemporary nature of the research landscape in this expanding field. This review reports the findings of a scoping review of the international empirical literature. The aim was to explore the relationship between child maltreatment and oral health and how this complex issue is addressed in contemporary dental, health, and social work practice. The review identified 68 papers, analysis of which identified three themes: (1) There is a relationship between poor oral health and child maltreatment that is well evidenced but conceptually underdeveloped. (2) There are discrepancies between the knowledge of members of the dental team about child maltreatment and their confidence and aptitude to identify and report child protection concerns. (3) There are areas of local-level policy and practice development that seek to improve working relationships between dentists and health and social work practitioners; however, there is widespread evidence that the oral health needs of this group of vulnerable children are not consistently met. To orientate critical discussion and planning for future research and practice, we present the Patterns, Advances, Gaps, Evidence for practice and Research recommendations (PAGER) framework. The review's findings are likely to be of interest to researchers, practitioners, and policy makers working across dentistry, health and social work.

The role of mask mandates, stay at home orders and school closure in curbing the COVID-19 pandemic prior to vaccination.

BACKGROUND: COVID-19 has quickly spread throughout the world, necessitating assessment of effective containment methods. The purpose of this study was to examine the impact of government mandated school closures, stay at home orders and mask requirements METHODS: Cumulative incidence rates were calculated at 14-day intervals until the day of the first vaccine administration in the country. Rate ratios were calculated using negative binomial regression while investigating the effects of adjusting for several sociodemographic and medical factors RESULTS: Faster implementation of mask mandates was consistently shown to be protective. States with mask mandates made at three to six months had a 1.61 times higher rate than those who implemented within one month (adjusted rate ratio = 1.61, 95% confidence interval: 1.23-2.10, P = .001). States with mask mandates made after 6 months or with no mandate had a 2.16 times higher rate than those who implemented within 1 month (adjusted rate ratio = 2.16, 95% confidence interval: 1.64-2.88, P < .0001). In contrast, both stay at home orders and school closures had no significant influence on disease trajectory. DISCUSSION: The benefits of mask mandates are apparent, especially when mandates were issued within a month. The impact of school closing and stay at home orders were less clear. CONCLUSIONS: Our results suggest that of the different physical distancing measures implemented by the government, mask mandates are the most important.

Knowledge, attitudes and practices of patients and healthcare professionals regarding oral health and COPD in São Paulo, Brazil: a qualitative study.

Poor oral health is associated with worse clinical outcomes in Chronic Obstructive Pulmonary Disease (COPD). This qualitative study aimed to investigate the knowledge, attitudes and practices of COPD patients and primary health care professionals (HCPs) in Brazil - where there are high rates of COPD and periodontal disease. Semi-structured interviews with COPD patients (n = 9) and three semi-structured focus groups with HCPs (n = 25) were conducted in São Paulo. Interviews were thematically analysed using The Framework Method. Despite a high prevalence of edentulism, patients viewed tooth loss and decay as a norm and neglected preventative oral health practices. HCPs blamed patients for avoiding preventative opportunities, whilst patients discussed significant barriers to oral healthcare. Knowledge of the relationship between oral health and COPD was lacking among HCPs and patients, but all participants were receptive to oral health education. Practitioners identified the need for a COPD primary care pathway that integrates oral health protocols. This study indicates that Brazil must incorporate preventative oral health into COPD management and expand public dental services to increase uptake.

Medical Student Perspectives on Their Role as Emerging Physicians During the COVID-19 Pandemic.

The COVID-19 pandemic caused a large strain on the US medical system, with shortage of medical personnel being a key issue. The role of medical school students during a pandemic is not well established. Understanding the perspectives of medical students with regard to their role is essential in determining how to facilitate the use of their skills in combating the pandemic. To evaluate medical student perspectives on the COVID-19 pandemic, an anonymous online survey was distributed to medical students, primarily in the Northeastern United States. In the sample of 232 students, there were significant differences between students in different class years when assessing moral obligations to assist with the COVID-19 pandemic (p = 0.002). A higher percentage of first and second year medical students (pre-clinical training, around 48%) felt that healthcare students are morally obligated to assist as compared to third and fourth year students (clinical training, 30.43% of third years and 23.19% of fourth years). In all class years, the majority said they would regret their decision if they had chosen not to study medicine (62.32% to 79.31%) and most students did not feel their motivation to become a physician had been decreased (84.78% to 87.50%). Though the study was limited because the majority of subjects were from New York, the results provide insight into medical students' attitudes about the COVID-19 pandemic and can be used in the planning of how best to utilize medical students in this and in future situations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01374-z.

Area-level deprivation and oral cancer in England 2012-2016.

BACKGROUND: The relationship between deprivation and oral cancer is complex. We examined magnitude and shape of deprivation-related inequalities in oral cancer in England 2012-2016. METHODS: Oral cancer was indicated by cancers of the lip and oral cavity (ICD10 C00-C06) and lip, oral cavity and pharynx (C00-C14) and deprivation by the Index of Multiple Deprivation. Deprivation inequality in incidence and mortality rates of oral cancer outcomes was measured using the Relative Index of Inequality (RII). Fractional polynomial regression was used to explore the shape of the relationships between deprivation and oral cancer outcomes. Multivariate regression models were fitted with the appropriate functions to examine the independent effect of deprivation on cancer adjusting for smoking, alcohol and ethnicity. RESULTS: Incidence rate ratios (IRRs) and mortality rate ratios (MRRs) were greater for more deprived areas. The RII values indicated significant inequalities for oral cancer outcomes but the magnitude of inequalities were greater for mortality. The relationships between deprivation and oral cancer outcomes were curvilinear. Deprivation, Asian ethnicity and alcohol consumption were associated with higher incidence and mortality rates of oral cancer. CONCLUSION: This is the first study, to our knowledge, exploring the shape of socioeconomic inequalities in oral cancer at neighbourhood level. Deprivation-related inequalities were present for all oral cancer outcomes with a steeper rise at the more deprived end of the deprivation spectrum. Deprivation predicted oral cancer even after accounting for other risk factors.

Loss-Framed Financial Incentives and Personalized Goal-Setting to Increase Physical Activity Among Ischemic Heart Disease Patients Using Wearable Devices: The ACTIVE REWARD Randomized Trial.

BACKGROUND: Regular physical activity reduces the risk of cardiovascular events, but most ischemic heart disease (IHD) patients do not obtain enough. METHODS AND RESULTS: ACTIVE REWARD (A Clinical Trial Investigating Effects of a Randomized Evaluation of Wearable Activity Trackers with Financial Rewards) was a 24-week home-based, remotely monitored, randomized trial with a 16-week intervention (8-week ramp-up incentive phase and 8-week maintenance incentive phase) and an 8-week follow-up. Patients used wearable devices to track step counts and establish a baseline. Patients in control received no other interventions. Patients in the incentive arm received personalized step goals and daily feedback for all 24 weeks. In the ramp-up incentive phase, daily step goals increased weekly by 15% from baseline with a maximum of 10 000 steps and then remained fixed. Each week, $14 was allocated to a virtual account; $2 could be lost per day for not achieving step goals. The primary outcome was change in mean daily steps from baseline to the maintenance incentive phase. Ischemic heart disease patients had a mean (SD) age of 60 (11) years and 70% were male. Compared with control, patients in the incentive arm had a significantly greater increase in mean daily steps from baseline during ramp-up (1388 versus 385; adjusted difference, 1061 [95% confidence interval, 386-1736]; P<0.01), maintenance (1501 versus 264; adjusted difference, 1368 [95% confidence interval, 571-2164]; P<0.001), and follow-up (1066 versus 92; adjusted difference, 1154 [95% confidence interval, 282-2027]; P<0.01). CONCLUSIONS: Loss-framed financial incentives with personalized goal setting significantly increased physical activity among ischemic heart disease patients using wearable devices during the 16-week intervention, and effects were sustained during the 8-week follow-up. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02531022.

Effect of an Automated Patient Dashboard Using Active Choice and Peer Comparison Performance Feedback to Physicians on Statin Prescribing: The PRESCRIBE Cluster Randomized Clinical Trial.

Importance: Statins are not prescribed to approximately 50% of patients who could benefit from them. Objective: To evaluate the effectiveness of an automated patient dashboard using active choice framing with and without peer comparison feedback on performance to nudge primary care physicians (PCPs) to increase guideline-concordant statin prescribing. Design, Setting, and Participants: This 3-arm cluster randomized clinical trial was conducted from February 21, 2017, to April 21, 2017, at 32 practice sites in Pennsylvania and New Jersey. Participants included 96 PCPs and 4774 patients not previously receiving statin therapy. Data were analyzed from April 25, 2017, to June 16, 2017. Interventions: Primary care physicians in the 2 intervention arms were emailed a link to an automated online dashboard listing their patients who met national guidelines for statin therapy but had not been prescribed this medication. The dashboard included relevant patient information, and for each patient, PCPs were asked to make an active choice to prescribe atorvastatin, 20 mg, once daily, atorvastatin at another dose, or another statin or not prescribe a statin and select a reason. The dashboard was available for 2 months. In 1 intervention arm, the email to PCPs also included feedback on their statin prescribing rate compared with their peers. Primary care physicians in the usual care group received no interventions. Main Outcomes and Measures: Statin prescription rates. Results: Patients had a mean (SD) age of 62.4 (8.3) years and a mean (SD) 10-year atherosclerotic cardiovascular disease risk score of 13.6 (8.2); 2625 (55.0%) were male, 3040 (63.7%) were white, and 1318 (27.6%) were black. In the active choice arm, 16 of 32 PCPs (50.0%) accessed the patient dashboard, but only 2 of 32 (6.3%) signed statin prescription orders. In the active choice with peer comparison arm, 12 of 32 PCPs (37.5%) accessed the patient dashboard and 8 of 32 (25.0%) signed statin prescription orders. Statins were prescribed in 40 of 1566 patients (2.6%) in the usual care arm, 116 of 1743 (6.7%) in the active choice arm, and 117 of 1465 (8.0%) in the active choice with peer comparison arm. In the main adjusted model, compared with usual care, there was a significant increase in statin prescribing in the active choice with peer comparison arm (adjusted difference in percentage points, 5.8; 95% CI, 0.9-13.5; P = .008), but not in the active choice arm (adjusted difference in percentage points, 4.1; 95% CI, -0.8 to 13.1; P = .11). Conclusions and Relevance: An automated patient dashboard using both active choice framing and peer comparison feedback led to a modest but significant increase in guideline-concordant statin prescribing rates. Trial Registration: ClinicalTrials.gov Identifier: NCT03021759.

Frequency gradients during two different forms of fibrillation in the canine atria.

BACKGROUND: Atrial fibrillation (AF) is thought to be sustained by multiple reentrant wavelets or firing foci. OBJECTIVE: The aim of this study was to compare the spectral domain characteristics in the left atrium (LA) and right atrium (RA) in two different models of AF. METHODS: Rectangular 8 x 14 electrode arrays were placed on the LA and RA of 14 anesthetized dogs. AF episodes were induced with burst pacing and aconitine in each dog. For each model, AF was induced from the RA in six dogs and from the LA in six dogs. Dominant frequencies (DFs) were obtained using the fast Fourier transform of the unipolar recordings obtained from each electrode of the array. Standard deviation (SD) was used to compute the frequency dispersion within an atrium. Regularity of the signal was quantified using an organization index (OI). RESULTS: DFs were largest in the atrium where aconitine was applied. Aconitine AF had larger gradients than burst-pacing AF (5.0 +/- 4.5 vs. 0.9 +/- 1.0 Hz: P <.006). Aconitine AF when compared with burst-pacing AF had greater absolute LA-RA differences in the SD of DFs (2.3 +/- 1.9 vs. 0.2 +/- 0.2 Hz; P <.001) and in OI (0.11 +/- 0.07 vs. 0.06 +/- 0.07; P <.07). CONCLUSIONS: Differences in frequency gradients and organization were observed during AF induced by burst pacing and aconitine. This suggests that different mechanisms of AF are possible and may be identified with frequency domain analysis.

Situational Strength Cues from Social Sources at Work: Relative Importance and Mediated Effects.

Situational strength is considered one of the most important situational forces at work because it can attenuate the personality-performance relationship. Although organizational scholars have studied the consequences of situational strength, they have paid little attention to its antecedents. To address this gap, the current study focused on situational strength cues from different social sources as antecedents of overall situational strength at work. Specifically, we examined how employees combine situational strength cues emanating from three social sources (i.e., coworkers, the immediate supervisor, and top management). Based on field theory, we hypothesized that the effect of situational strength from coworkers and immediate supervisors (i.e., proximal sources of situational strength) on employees' perceptions of overall situational strength on the job would be greater than the effect of situational strength from the top management (i.e., the distal source of situational strength). We also hypothesized that the effect of situational strength from the distal source would be mediated by the effects of situational strength from the proximal sources. Data from 363 full-time employees were collected at two time points with a cross-lagged panel design. The former hypothesis was supported for one of the two situational strength facets studied. The latter hypothesis was fully supported.

Robotic Automation of In Vivo Two-Photon Targeted Whole-Cell Patch-Clamp Electrophysiology.

Whole-cell patch-clamp electrophysiological recording is a powerful technique for studying cellular function. While in vivo patch-clamp recording has recently benefited from automation, it is normally performed "blind," meaning that throughput for sampling some genetically or morphologically defined cell types is unacceptably low. One solution to this problem is to use two-photon microscopy to target fluorescently labeled neurons. Combining this with robotic automation is difficult, however, as micropipette penetration induces tissue deformation, moving target cells from their initial location. Here we describe a platform for automated two-photon targeted patch-clamp recording, which solves this problem by making use of a closed loop visual servo algorithm. Our system keeps the target cell in focus while iteratively adjusting the pipette approach trajectory to compensate for tissue motion. We demonstrate platform validation with patch-clamp recordings from a variety of cells in the mouse neocortex and cerebellum.

Effect of Financial Incentives on Glucose Monitoring Adherence and Glycemic Control Among Adolescents and Young Adults With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Glycemic control often deteriorates during adolescence and the transition to young adulthood for patients with type 1 diabetes. The inability to manage type 1 diabetes effectively during these years is associated with poor glycemic control and complications from diabetes in adult life. Objective: To determine the effect of daily financial incentives on glucose monitoring adherence and glycemic control in adolescents and young adults with type 1 diabetes. Design, Setting, and Participants: The Behavioral Economic Incentives to Improve Glycemic Control Among Adolescents and Young Adults With Type 1 Diabetes (BE IN CONTROL) study was an investigator-blinded, 6-month, 2-arm randomized clinical trial conducted between January 22 and November 2, 2016, with 3-month intervention and follow-up periods. Ninety participants (aged 14-20) with suboptimally controlled type 1 diabetes (hemoglobin A1c [HbA1c] >8.0%) were recruited from the Diabetes Center for Children at the Children's Hospital of Philadelphia. Interventions: All participants were given daily blood glucose monitoring goals of 4 or more checks per day with 1 or more level within the goal range (70-180 mg/dL) collected with a wireless glucometer. The 3-month intervention consisted of a $60 monthly incentive in a virtual account, from which $2 was subtracted for every day of nonadherence to the monitoring goals. During a 3-month follow-up period, the intervention was discontinued. Main Outcomes and Measures: The primary outcome was change in HbA1c levels at 3 months. Secondary outcomes included adherence to glucose monitoring and change in HbA1c levels at 6 months. All analyses were by intention to treat. Results: Of the 181 participants screened, 90 (52 [57.8%] girls) were randomized to the intervention (n = 45) or control (n = 45) arms. The mean (SD) age was 16.3 (1.9) years. The intervention group had significantly greater adherence to glucose monitoring goals in the incentive period (50.0% vs 18.9%; adjusted difference, 27.2%; 95% CI, 9.5% to 45.0%; P = .003) but not in the follow-up period (15.3% vs 8.7%; adjusted difference, 3.9%; 95% CI, -2.0% to 9.9%; P = .20). The change in HbA1c levels from baseline did not differ significantly between groups at 3 months (adjusted difference, -0.08%; 95% CI, -0.69% to 0.54%; P = .80) or 6 months (adjusted difference, 0.03%; 95% CI, -0.55% to 0.60%; P = .93). Conclusions and Relevance: Among adolescents and young adults with type 1 diabetes, daily financial incentives improved glucose monitoring adherence during the incentive period but did not significantly improve glycemic control. Trial Registration: clinicaltrials.gov Identifier: NCT02568501.