The Role of Pancreatitis Risk Genes in Endocrine Insufficiency Development After Acute Pancreatitis in Children.

BACKGROUND AND AIMS: Acute pancreatitis (AP) is increasingly recognized as a risk factor for diabetes mellitus (DM). We aimed to study the association of pancreatitis genes with pancreatic endocrine insufficiency (pre-DM and DM) development post AP in children. METHODS: This was an observational cohort study that enrolled subjects ≤21 years with their first episode of AP and followed them for 12 months for the development of pancreatic endocrine insufficiency. Pancreatitis risk genes (CASR, CEL, CFTR, CLDN2, CPA1, CTRC, PRSS1, SBDS, SPINK1, and UBR1) were sequenced. A genetic risk score was derived from all genes with univariable p<0.15 RESULTS: A total 120 subjects with AP were genotyped. Sixty-three subjects (52.5%) had at least 1 reportable variant identified. For modeling the development of pancreatic endocrine insufficiency at one year, 6 were excluded (2 with DM at baseline, 3 with total pancreatectomy, and 1 death).. From this group of 114, 95 remained normoglycemic and 19 (17%) developed endocrine insufficiency (4 DM, 15 pre-DM). Severe AP (58% vs 20%; p=0.001) and at least one gene affected (79% vs 47%, p=0.01) were enriched among the endocrine insufficient group. Those with versus without endocrine insufficiency were similar in age, sex, race, ethnicity, body mass index, and AP recurrence. A model for pre-DM/DM development included AP severity (OR=5.17 [1.66, 16.15], p=0.005) and genetic risk score (OR=4.89 [1.83, 13.08], p=0.002) and had an AUC of 0.74. CONCLUSIONS: In this cohort of children with AP, pancreatitis risk genes and AP disease severity were associated with pre-DM or DM development post AP.

Faster discharge with lactated ringers than normal saline in first 72 h of acute pancreatitis: A multicenter randomized trial.

OBJECTIVES: Data driven strategies for acute pancreatitis (AP) in pediatrics are limited; adult data suggests lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes, but has not been studied in pediatrics. Our objective was to evaluate the efficacy of LR during the first 48 h of an AP episode compared with NS. STUDY DESIGN: A multisite randomized controlled clinical trial, from 2015 to 2020 (Clinical Trials.gov NCT03242473). Patients were randomized to exclusively LR or NS for the first 48 h. Primary outcomes were serial C-reactive protein (CRP) values. Secondary outcomes included other lab values, time to feeds, length of stay (LOS), systemic inflammatory response syndrome (SIRS) development, and progression to severe AP (SAP). RESULTS: We studied 76 patients (38 LR, 38 NS). CRP at 24 and 48 h were not significantly different between LR or NS group. Additionally, there were no differences in trends of BUN, amylase, lipase, SIRS status, or SAP development between the LR and NS group at 24 and 48 h. A higher proportion of LR patients (32%, 12/38) were discharged before 48 h compared to NS (13%, 5/38). The LR group had a significantly higher rate of discharge within the first 72 h compared to the NS group (p = 0.02). CONCLUSION: The use of LR was associated with a faster rate of discharge during the intervention period and in the first 72 h, but no other differences compared to NS. This reduction in length of hospitalization has significant implications for patients and healthcare costs.

Implementation of a Clinical Leadership Curriculum for Pediatric Residents.

Introduction: Clinical leadership is an essential skill for physicians, empowering them to lead and coordinate teams, communicate clearly under various conditions, model positive behaviors, display emotional intelligence, and ultimately improve patient care outcomes. However, there are currently no standardized residency curricula or competency-based assessments for clinical leadership, as residents often assimilate leadership skills through trial-and-error or observation of their clinical faculty. By utilizing a comprehensive needs assessment and synthesizing evidence-based practices, we developed and implemented a longitudinal and skills-based clinical leadership curriculum for pediatric residents. Methods: We modeled our clinical leadership curriculum after Kern's 6-step approach to curricular development and the Accreditation Council for Graduate Medical Education competency requirements for professionalism. We identified topics based on a resident needs assessment and synthesized evidence from published practices. The curriculum was implemented through both monthly facilitated group sessions and independent learning modules. Results: 44 postgraduate year-2 (PGY-2) and PGY-3 pediatric residents participated in at least one monthly session of the clinical leadership curriculum. 27 (61%) completed the survey to evaluate the efficacy of the curriculum. Of the respondents, 23 (85%) residents found the leadership sessions useful, 4 (15%) were neutral, and none (0%) rated the sessions as not useful. 26 (96%) residents reported that the sessions should be continued. Conclusion: The clinical leadership curriculum has been received favorably by senior pediatric residents at our institution. Our next steps are to pilot the curriculum within residency programs of different specialties at our own institution as well as with pediatric residencies at other institutions.

Matrix metalloproteinases and their inhibitors in pediatric severe acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is increasing in incidence in adult and pediatric patients. Identification of patients at high risk for progression to severe acute pancreatitis (SAP) is crucial, as it can lead to increased mortality and health system cost. Matrix metalloproteinases (MMPs) are endopeptidases which degrade extracellular matrix proteins and increase activity of pro-inflammatory cytokines. Tissue inhibitors of metalloproteinases (TIMPs) regulate MMP activity. Prior limited studies of MMPs and TIMPs have found some to be associated with development of SAP. The aim of this study was to further investigate the role of MMPs and TIMPs in detecting pediatric patients at risk for developing moderately severe AP or SAP. METHODS: Plasma samples were prospectively collected for patients <21 years of age presenting with AP between November 2015 and October 2019, along with healthy controls. Bead-based multiplex assays were utilized to test levels of 12 MMPs and TIMPs. RESULTS: Samples were collected from 7 subjects who developed SAP, 7 with moderately severe AP, 45 with mild AP and 44 healthy controls. MMP-9 (p = 0.04) and TIMP-1 (p = 0.01) levels were significantly higher in SAP patients. A multivariable logistic regression model using MMP-9 and TIMP-1 predicted SAP (AUROC 0.87, 95% CI 0.76-0.98). CONCLUSION: We have demonstrated that MMP9 and TIMP1 levels are increased at AP presentation in pediatric patients who developed SAP during the course of illness. Further studies are needed to validate the use of MMPs and TIMPs as predictive tools for development of SAP in pediatric pancreatitis.

Cytokine Profile Elevations on Admission Can Determine Risks of Severe Acute Pancreatitis in Children.

OBJECTIVES: To utilize a Luminex platform to examine multiple cytokines simultaneously as well as clinical laboratory testing to identify markers that predict acute pancreatitis severity in the pediatric population on admission. STUDY DESIGN: Patients (<19 years of age) prospectively enrolled over a 4-year period in a single institution acute pancreatitis database were included in separate derivation and validation cohorts. Plasma samples were obtained within 48 hours of admission and stored for analysis. Samples from mild acute pancreatitis and severe acute pancreatitis (moderately severe and severe combined) were analyzed using Luminex panels and C-reactive protein (CRP) testing. RESULTS: The derivation cohort examined 62 cytokines in 66 subject samples (20 control, 36 mild acute pancreatitis, 10 severe acute pancreatitis) and identified interleukin 6 (IL-6) (P = .02) and monocyte chemotactic protein-1 (MCP-1) (P = .02) as cytokines that were differentially expressed between mild and severe acute pancreatitis. Our validation cohort analyzed 76 cytokines between 10 controls, 19 mild acute pancreatitis, and 6 severe acute pancreatitis subjects. IL-6 (P = .02) and MCP-1 (P = .007) were again found to differentiate mild acute pancreatitis from severe acute pancreatitis. CRP values were obtained from 53 of the subjects, revealing a strong association between elevated CRP values and progression to severe disease (P < .0001). CONCLUSIONS: This study identified and validated IL-6 and MCP-1 as predictors of severe acute pancreatitis using 2 distinct cohorts and showed that CRP elevation is a marker of progression to severe acute pancreatitis. These biomarkers have not been extensively studied in the pediatric acute pancreatitis population. Our data allows for risk-stratification of patients with acute pancreatitis, and represent novel insight into the immunologic response in severe acute pancreatitis.

Assessment of Clinical Leadership Training Needs in Senior Pediatric Residents.

INTRODUCTION: Although clinical leadership in physicians is associated with improved healthcare, leadership training is rarely integrated into residency training. Our objective was to perform a comprehensive needs assessment of our pediatric residents' existing leadership experiences and knowledge and to identify training gaps within our program. METHODS: First, we held focus groups with senior pediatric residents to understand their clinical leadership experiences and identify training needs. Notes were transcribed and independently coded by 2 researchers, with thematic saturation achieved. Next, we focused each session on 1 leadership content area identified from the aforementioned themes to better understand the specific training needs for each topic. RESULTS: Four major themes were identified: (1) Effective and timely communication with supervisors, learners, ancillary staff, and patients is indispensable in promoting safe patient care, avoiding conflict, and preventing misunderstanding. (2) Training in teaching methods is desired, especially gaining the skills needed to teach various levels of learners, in different settings and under time constraints. (3) Time management, availability of resources, and team logistics were often learned through trial-and-error. (4) Self-care, self-acceptance, emotional regulation, and peer debriefing are relied upon to manage negative emotions; rarely are resilience and wellness strategies employed in "real-time." CONCLUSION: Senior residents currently face gaps in clinical leadership training and may benefit from additional instruction in content areas related to these 4 themes. Our next steps are to utilize the identified themes to develop a longitudinal and skills-based clinical leadership curriculum to address the gap in graduate medical education.

An In-Situ Assessment of Wood-in-Service Using Microwave Technologies, with a Focus on Assessing Hardwood Power Poles.

Wooden power poles and their ongoing inspection represent a significant investment for most electrical power utilities. This study explored the potential for using microwave fields to non-invasively assess the state of hardwood power poles in a field experiment. Two strategies were assessed: 2.4 GHz microwave field transmission through the pole; and mutual coupling between antennae using a 10.525 GHz radar module applied to the surface of the pole. Both systems distinguished between sound hardwood poles and those which were compromised by decay and subterranean termite attack and infestation.

Who's at Risk? A Prognostic Model for Severity Prediction in Pediatric Acute Pancreatitis.

OBJECTIVES: The aim of the study was to validate and optimize a severity prediction model for acute pancreatitis (AP) and to examine blood urea nitrogen (BUN) level changes from admission as a severity predictor. STUDY DESIGN: Patients from 2 hospitals were included for the validation model (Children's Hospital of the King's Daughters and Children's National Hospital). Children's Hospital of the King's Daughters and Cincinnati Children's Hospital Medical Center data were used for analysis of BUN at 24 to 48 hours. RESULTS: The validation cohort included 73 patients; 22 (30%) with either severe or moderately severe AP, combined into the all severe AP (SAP) group. Patients with SAP had higher BUN (P = 0.002) and lower albumin (P = 0.005). Admission BUN was confirmed as a significant predictor (P = 0.005) of SAP (area under the receiver operating characteristic [AUROC] 0.73, 95% confidence interval [CI] 0.60-0.86). Combining BUN (P = 0.005) and albumin (P = 0.004) resulted in better prediction for SAP (AUROC 0.83, 95% CI 0.72-0.94). A total of 176 AP patients were analyzed at 24-48 hours; 39 (22%) met criteria for SAP. Patients who developed SAP had a significantly higher BUN (P < 0.001) after 24 hours. Elevated BUN levels within 24 to 48 hours were independently predictive of developing SAP (AUROC: 0.76, 95% CI: 0.66-0.85). Patients who developed SAP had a significantly smaller percentage decrease in BUN from admission to 24 to 48 hours (P = 0.002). CONCLUSION: We externally validated the prior model with admission BUN levels and further optimized it by incorporating albumin. We also found that persistent elevation of BUN is associated with development of SAP. Our model can be used to risk stratify patients with AP on admission and again at 24 to 48 hours.

Use of Lactated Ringers Solution Compared With Normal Saline Is Associated With Shorter Length of Stay in Pediatric Acute Pancreatitis.

OBJECTIVE: The aim of the study was to evaluate lactated ringers (LR) versus normal saline (NS) in pediatric acute pancreatitis (AP). METHODS: This retrospective study used Pediatric Health Information System database of primary AP patients, 2013 to 2017. RESULTS: The study included 1581 first time AP patients with exclusive use of a single fluid (111 LR, 1470 NS) for the first 48 hours. The LR cohort had a significantly shorter length of stay (P < 0.001) compared with NS. A multivariable logistic regression analysis suggests use of NS in the first 48 hours (after controlling for total parenteral nutrition, operation, and infection during the admission) had a significantly increased likelihood of requiring a hospitalization for 4 days or more compared with the LR group (odds ratio, 3.31; 95% confidence interval, 1.95-5.62). The overall cost was significantly less in the LR group. There was no statistical difference observed in risk factors for AP, intensive care transfer, organ dysfunction, or mortality. CONCLUSIONS: This represents the first large data set analysis of LR versus NS in pediatric AP. The use of LR was associated with a shorter length of stay and reduced cost compared with NS. Future randomized trials will help determine the ideal fluid choice for pediatric AP.

Spin Lock Adiabatic Correction (SLAC) for B1-insensitive pulse design at 7T.

A new framework for B1 insensitive adiabatic pulse design is proposed, denoted Spin Lock Adiabatic Correction (SLAC), which counteracts deviations from ideal behaviour through inclusion of an additional correction component during pulse design. SLAC pulses are theoretically derived, then applied to the design of enhanced BIR-4 and hyperbolic secant pulses to demonstrate practical utility of the new pulses. At 7T, SLAC pulses are shown to improve the flip angle homogeneity compared to a standard adiabatic pulse with validation in both simulations and phantom experiments, under SAR equivalent experimental conditions. The SLAC framework can be applied to any arbitrary adiabatic pulse to deliver excitation with increased B1 insensitivity.

Analysis of Penalties Imposed on Organisations for Breaching Safety and Health Regulations in the United Kingdom.

BACKGROUND: The study analyzes penalties imposed on organizations for breaching safety and health regulations. The research questions are as follows: what are the commonly breached safety and health regulations? How proportional are penalties imposed on organizations for breaching health and safety regulations in the United Kingdom? METHODS: The study employed sequential explanatory mixed research strategies for better understanding of health and safety penalties imposed on organizations. Actual health and safety convictions and penalties data for 10 years (2006 to 2016) were obtained through the United Kingdom Health and Safety Executive (HSE) public register for convictions. Overall, 2,217 health and safety cases were analyzed amounting to total fines of £37,179,916, in addition to other wide-ranging penalties. For thorough understanding, eight interviews were conducted with industry practitioners, lawyers, and HSE officials as part of the study qualitative data. RESULTS: Findings show that the Health and Safety at Work (HSW) Act accounted for 46% of all HSE prosecution cases in the last decade. This is nearly half of the total safety and health at work prosecutions. Moreover, there is widespread desire for organizations to comply with the HSW Act, but route fines are seen as burdensome and inimical to business growth. CONCLUSION: A key deduction from the study reveal significant disproportionality concerning penalties imposed on organizations for breaching safety and health regulations. On aggregate, small companies tend to pay more for health and safety offenses in a ratio of 1:2 compared to large companies. The study also reveals that the HSW Act accounted for nearly half of the total safety and health at work prosecutions in the last decade.

The tibial bayonet method of wound closure.

Management of open lower limb fractures with soft tissue defects can be a technically challenging orthopaedic problem. Limited availability of orthoplastic services means that alternatives to the fix and flap concept are required in order to prevent infected non-unions from developing. The proposed 'bayonet apposition' allows the surgeon to temporarily shorten the limb without angulating the limb or creating a bone defect and removing viable bone. The viable bone edges are overlapped in a bayonet-like manner in order to appose the wound and skin edges. The limb length is restored by gradually distracting the bone segments once the soft tissues have healed. This is facilitated with a hexapod fixator for stabilization of the fracture and distraction. Prerequisites for utilizing this method are circumferential soft tissue damage to the lower limb with viable distal tissue. The bayonet method allows primary closure of a wound and rapid restoration of the native length of the limb.

Recognition and treatment of sleep-disordered breathing: an important component of chronic disease management.

Sleep-disordered breathing (SDB) is a highly prevalent condition, and is associated with many debilitating chronic diseases. The role of untreated obstructive sleep apnea (OSA) in arterial hypertension has been recognized in international guidelines. Treatment with continuous positive airway pressure (CPAP) is associated with clinically-relevant reductions in blood pressure. In heart failure (HF), SDB is associated with worse prognosis and increased mortality. Major HF guidelines recommend that patients should be treated for sleep apnea to improve their HF status. Severe OSA increases the risk of arrhythmias, including atrial fibrillation, influences risk management in stroke, and is highly prevalent in patients with type 2 diabetes. Effective treatment with CPAP improves the success of antiarrhythmic interventions, improves outcomes in stroke and reduces hyperglycemia in diabetes. Patients with coronary artery disease also have a high prevalence of SDB, which is independently associated with worse outcomes. The role of CPAP for secondary cardiovascular prevention remains to be determined. Data from large, well-conducted clinical trials have shown that noninvasive ventilation, targeted to markedly reduce hypercapnia, significantly improves survival and reduces readmission in stable hypercapnic chronic obstructive pulmonary disease. The association of SDB with chronic diseases contributes to the high healthcare costs incurred by SDB patients. SDB also has an important negative impact on quality of life, which is reversed by CPAP treatment. The high prevalence of SDB, and its association with diseases that cause significant morbidity and mortality, suggest that the diagnosis and management of SDB is an important therapeutic goal. First, adherent CPAP treatment significantly improves the quality of life of all patients with SDB; second, it eliminates the negative impact of untreated SDB on any associated chronic diseases; and third, it significantly reduces the increased costs of all hospital and medical services directly associated with untreated SDB. In short, the recognition and treatment of SDB is vital for the continued health and wellbeing of individual patients with SDB.

Cultural universality and specificity of student engagement in school: The results of an international study from 12 countries.

BACKGROUND: A comprehensive understanding of the contextual factors that are linked to student engagement requires research that includes cross-cultural perspectives. AIMS: This study investigated how student engagement in school is associated with grade, gender, and contextual factors across 12 countries. It also investigated whether these associations vary across countries with different levels of individualism and socio-economic development. SAMPLES: The participants were 3,420 7th, 8th, and 9th grade students from Austria, Canada, China, Cyprus, Estonia, Greece, Malta, Portugal, Romania, South Korea, the United Kingdom, and the United States. METHODS: The participants completed a questionnaire to report their engagement in school, the instructional practices they experienced, and the support they received from teachers, peers, and parents. Hierarchical linear modelling was used to examine the effects at both student and country levels. RESULTS: The results across countries revealed a decline in student engagement from Grade 7 to Grade 9, with girls reporting higher engagement than boys. These trends did not vary across the 12 countries according to the Human Development Index and Hofstede's Individualism Index. Most of the contextual factors (instructional practices, teacher support, and parent support) were positively associated with student engagement. With the exception that parent support had a stronger association with student engagement in countries with higher collectivism, most of the associations between the contextual factors and student engagement did not vary across countries. CONCLUSIONS: The results indicate both cultural universality and specificity regarding contextual factors associated with student engagement in school. They illustrate the advantages of integrating etic and emic approaches in cross-cultural investigations.

Solving the Bloch equation with periodic excitation using harmonic balancing: application to Rabi modulated excitation.

In waveform design for magnetic resonance applications, periodic continuous-wave excitation offers potential advantages that remain largely unexplored because of a lack of understanding of the Bloch equation with periodic continuous-wave excitations. Using harmonic balancing techniques the steady state solutions of the Bloch equation with periodic excitation can be effectively solved. Moreover, the convergence speed of the proposed series approximation is such that a few terms in the series expansion suffice to obtain a very accurate description of the steady state solution. The accuracy of the proposed analytic approximate series solution is verified using both a simulation study as well as experimental data derived from a spherical phantom with doped water under continuous-wave excitation. Typically a five term series suffices to achieve a relative error of less than one percent, allowing for a very effective and efficient analytical design process. The opportunities for Rabi frequency modulated continuous-wave form excitation are then explored, based on a comparison with steady state free precession pulse sequences.

Dielectric properties of liquid phase molecular clusters using the external field method: molecular dynamics study.

We analyzed the dielectric properties of molecular liquids using the external field method with reaction field approximations. The applicability of this method to determine the dielectric properties of molecules with zero (1,4-dioxane) and non-zero (water and bio-molecular aqueous solutions) permanent dipole moment was studied. The relative static dielectric constant obtained using the external field method for polar and non-polar molecular liquids, including molecules with zero permanent dipole moment, agreed well with the experimental values presented in the literature. Our results indicate that the Debye relaxation time constants estimated from the non-equilibrium simulations using the external field method were accurate for molecules whose permanent dipole moments were less than 12 D.

Understanding and measuring student engagement in school: the results of an international study from 12 countries.

The objective of the present study was to develop a scale that is appropriate for use internationally to measure affective, behavioral, and cognitive dimensions of student engagement. Psychometric properties of this scale were examined with data of 3,420 students (7th, 8th, and 9th grade) from 12 countries (Austria, Canada, China, Cyprus, Estonia, Greece, Malta, Portugal, Romania, South Korea, the United Kingdom, and the United States). The intraclass correlation of the full-scale scores of student engagement between countries revealed that it was appropriate to aggregate the data from the 12 countries for further analyses. Coefficient alphas revealed good internal consistency. Test-retest reliability coefficients were also acceptable. Confirmatory factor analyses indicated that the data fit well to a second-order model with affective, behavioral, and cognitive engagement as the first-order factors and student engagement as the second-order factor. The results support the use of this scale to measure student engagement as a metaconstruct. Furthermore, the significant correlations of the scale with instructional practices, teacher support, peer support, parent support, emotions, academic performance, and school conduct indicated good concurrent validity of the scale. Considerations and implications regarding the international use of this student engagement in school measure are discussed.

Rabi resonance in spin systems: theory and experiment.

The response of a magnetic resonance spin system is predicted and experimentally verified for the particular case of a continuous wave amplitude modulated radiofrequency excitation. The experimental results demonstrate phenomena not previously observed in magnetic resonance systems, including a secondary resonance condition when the amplitude of the excitation equals the modulation frequency. This secondary resonance produces a relatively large steady state magnetisation with Fourier components at harmonics of the modulation frequency. Experiments are in excellent agreement with the theoretical prediction derived from the Bloch equations, which provides a sound theoretical framework for future developments in NMR spectroscopy and imaging.