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Background and Objectives: Extensive literature supports using dexamethasone (DEX) in children presenting to the emergency department (ED) with mild-to-moderate asthma exacerbations; however, only limited studies have assessed this in hospitalized children. In this study, we evaluate the outcomes of DEX versus prednisone/prednisolone (PRED) use in children hospitalized for mild-to-moderate asthma exacerbations., Methods: This multisite retrospective cohort study included children between 3 and 21 years of age hospitalized to a tertiary care children's hospital system between January 1, 2013, and December 31, 2017, with a primary discharge diagnosis of acute asthma exacerbation or status asthmaticus. Primary study outcome was mean hospital length of stay (LOS). Secondary outcomes included PICU transfers during initial hospitalization and ED revisits and hospital readmissions within 10 days after discharge. Generalized linear models were used to model logged LOS as a function of steroid and demographic and clinical covariates. The analysis was stratified by initial steroid timing., Results: Of the 1410 children included, 981 received only DEX and 429 received only PRED. For children who started oral steroids after hospital arrival, DEX cohort had a significantly shorter adjusted mean hospital LOS (DEX 24.43 hours versus PRED 29.38 hours; P = .03). For children who started oral steroids before hospital arrival, LOS did not significantly differ (DEX 26.72 hours versus PRED 25.20 hours; P = .45). Rates of PICU transfers, ED revisits, and hospital readmissions were uncommon events., Conclusion: Children hospitalized with mild-to-moderate asthma exacerbations have significantly shorter hospital LOS when starting DEX rather than PRED on admission., Competing Interests: POTENTIAL CONFLICT OF INTEREST:, (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: The primary objective is to describe the relationship between the days supplied of postsurgical filled opioid prescriptions and refills., Background: The American College of Surgeons (ACS) has called for surgeons to alter opioid prescribing to counteract the opioid epidemic while simultaneously providing pain relief. However, there is insufficient evidence to inform perioperative prescribing guidelines and quality metrics in children., Methods: We performed a secondary data analysis of nationwide commercial claims from the Health Care Cost Institute (HCCI) data spanning 2010 and 2014. Based on initial opioid fill and refill rates for 11 common pediatric procedures, the refill analysis focused on anterior cruciate ligament repair, humerus fracture repair, cholecystectomy, posterior spinal fusion, and tonsillectomy., Results: There were 178,990 cases with a median age of 6. Overall, 48.5% of patients filled an opioid prescription between 30 days before surgery through 7 days after surgery, and 14.2% filled a second opioid prescription within 30 days. There was a significant negative relationship between days supplied in the initial prescription and probability of a refill for humerus fracture, spinal fusion, and tonsillectomy. The largest effect was seen for tonsillectomy, with the odds of having a refill decreasing by approximately 12% for each day supplied in the initial prescription (odds ratio 0.88, 95% confidence interval 0.87-0.89, P < 0.001)., Conclusions: Pediatric postoperative opioid-prescribing guidelines need to be procedure-specific and based on patient age. We provide the days supplied associated with a 20% probability of a refill by age to further guideline development., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Discourse connectives are lexical items like "but" and "so" that are well-known to influence the online processing of the discourse relations they convey. Yet, discourse relations like causality or contrast can also be signaled by other means than connectives, such as syntactic structures. So far, the influence of these alternative signals for discourse processing has been comparatively under-researched. In particular, their processing in a second language remains entirely unexplored. In a series of three self-paced reading experiments, we compare the reading patterns of contrastive relations by native French-speakers and non-native speakers of French with English as a first language. We focus on the effect of syntactic parallelism and how it interacts with different types of connectives. We test whether native and non-native readers equally recruit parallelism to process contrast in combination with or without a connective (Experiment 1), with a frequent vs. infrequent connective (Experiment 2) and with an ambiguous vs. unambiguous connective (Experiment 3), thus varying the explicitness and ease of retrieval of the contrast relation. Our results indicate that parallelism plays an important role for both groups of readers, but that it is a more prominent cue for non-native speakers, while its effect is modulated by task difficulty for native participants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Crible, Wetzel and Zufferey.)

Background/objectives: Firearm injuries are converging with motor vehicle collisions (MVC) as the number one cause of death for children in the United States. Thus we examine differences in hospital cost and hospital resource utilization between motor vehicle and firearm injury., Methods: This retrospective, cross-sectional study compares hospital costs and resource utilization of motor vehicle and firearm-injured children aged 0 to 19 years of age over a 5-year time frame (January 1, 2013-December 31, 2017) in 35 freestanding children's hospitals that submitted data to the Pediatric Health Information System. The primary outcome was hospital-adjusted comparative cost per patient presentation. Generalized linear mixed models were used to quantify the relationship between the type of injury and each outcome, adjusting for patient characteristics and hospital., Results: There were 89,133 emergency department (ED) visits attributed to MVCs and 3,235 for firearm injury. Of the youths who presented for firearm injury, 49% were hospitalized versus 14% of youths presenting with MVC (adjusted odds ratio [aOR] = 6.6, 95% confidence interval [CI] = 6.1 to 7.2). Youths with firearm injury were more likely to be admitted to an intensive care unit (aOR = 6.7, 95% CI = 5.9 to 7.7) and had longer lengths of stays (aOR = 2.2, 95% CI = 1.9 to 2.6) compared to their MVC counterparts. Children admitted for firearm injury had more imaging and ED return visits, along with subsequent inpatient admission within 3 days (aOR = 3.4, 95% CI = 2.1 to 5.5) and 1 year (aOR = 2.5, 95% CI = 2.1 to 2.9). The mean relative per-patient costs were nearly fivefold higher for the firearm-injured group., Conclusions: Hospital costs and markers of resource utilization were higher for youths with firearm injury compared to MVC. High medical resource utilization is one of several important reasons to advocate for a comparable national focus and funding on firearm-related injury prevention., (© 2021 Society for Academic Emergency Medicine.)

Background: This prospective clinical study aimed to investigate a possible deviation between the digitally planned implant position and the position achieved using dynamic navigation. The aim of the study was to establish clinical effectiveness and precision of implantation using dynamic navigation., Methods: Twenty consecutive patients received an implant (iSy-Implantat, Camlog, Wimsheim, Germany). One screw implant was placed in one jaw with remaining dentition of at least six teeth. The workflow was fully digital. Digital implant planning was conducted using cone-beam computed tomography (CBCT) and an intraoral scan of the actual condition. Twenty implants were subsequently placed using a dynamic computer-assisted procedure. The clinical situation of the implant position was recorded using an intraoral scan. Using these data, models were produced via 3D printing, and CBCTs of these models were made using laboratory analogs. Deviations of the achieved implant position from the planned position were determined using evaluation software., Results: The evaluation of 20 implants resulted in a mean angle deviation of 2.7° (95% CI 2.2-3.3°). The 3D deviation at the implant shoulder was 1.83 mm (95% CI 1.34-2.33 mm). No significant differences were found for any of the parameters between the implantation in the upper or lower jaw and an open or flapless procedure ( p -value < 0.05)., Conclusion: The clinical trial showed that sufficiently precise implantation was possible with the dynamic navigation system used here. Dynamic navigation can improve the quality of implant positioning. In particular, the procedure allows safe positioning of the implants in minimally invasive procedures, which usually cannot be performed freehand in this form. A clinical benefit and effectiveness can be determined from the results.

Background: Feeding difficulty is a known complication of congenital heart surgery. Despite this, there is a relative sparsity in the available data regarding risk factors, incidence, associated symptoms, and outcomes., Methods: In this retrospective chart review, patients aged 0-18 years who underwent congenital heart surgery at a single institution between January and December, 2017 were reviewed. Patients with feeding difficulties before surgery, multiple surgeries, and potentially abnormal recurrent laryngeal nerve anatomy were excluded. Data collected included patient demographics, feeding outcomes, post-operative symptoms, flexible nasolaryngoscopy findings, and rates of readmission within a 1-year follow-up period. Multivariable regression analyses were performed to evaluate the risk of an alternative feeding plan at discharge and length of stay., Results: Three-hundred and twenty-six patients met the inclusion criteria for this study. Seventy-two (22.09%) were discharged with a feeding tube and 70 (97.22%) of this subgroup were younger than 12 months at the time of surgery. Variables that increased the risk of being discharged with a feeding tube included patient age, The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score, procedure group, aspiration, and reflux. Speech-language pathology was the most frequently utilised consulting service for patients discharged with feeding tubes (90.28%) while other services were not frequently consulted. The median length of stay was increased from 4 to 10 days for patients who required an enteral feeding tube at discharge., Discussion: Multidisciplinary management protocol and interventions should be developed and standardised to improve feeding outcomes following congenital heart surgery.

The aim of this in vitro study was to determine whether the process chain influences the accuracy of a computer-assisted dynamic navigation procedure. Four different data integration workflows using cone-beam computed tomography (CBCT), conventional impressions, and intraoral digitization with and without reference markers were analyzed. Digital implant planning was conducted using data from the CBCT scans and 3D data of the oral models. The restoration of the free end of the lower jaw was simulated. Fifteen models were each implanted with two new teeth for each process chain. The models were then scanned with scan bodies screwed onto the implants. The deviations between the planned and achieved implant positions were determined. The evaluation of all 120 implants resulted in a mean angular deviation of 2.88 ± 2.03°. The mean 3D deviation at the implant shoulder was 1.53 ± 0.70 mm. No significant differences were found between the implant regions. In contrast, the workflow showed significant differences in various parameters. The position of the reference marker affected the accuracy of the implant position. The in vitro examination showed that precise implantation is possible with the dynamic navigation system used in this study. The results are of the same order of magnitude that can be achieved using static navigation methods. Clinical studies are yet to confirm the results of this study.

Introduction: Deaths due to an opioid overdose nearly doubled from 2013 to 2017. Our objective is to describe the trends in intent, healthcare resource use, and clinical outcomes among adults with opioid exposures., Materials and Methods: This study is a retrospective analysis of data from the 55 U.S. poison control centers. Adults, >19 years, with an opioid as the primary poisoning agent between 2005 and 2018 were included. These years were divided into three epochs (2005-2009, 2010-2014, and 2015-2018) to describe the trends in frequency, intent, severity, healthcare resource use, and regional differences in U.S. adults affected by prescription and illicit opioid exposures., Results: A total of 546,049 (54.4%) of the 1,002,947 opioid-related cases reported to the U.S. poison centers met inclusion criteria. The percentage of patients with a moderate/major clinical effect increased in each epoch (24.4, 29.13, and 35.3%) as did the proportion of patients with illicit opioids (coded as heroin) as their primary substance (2.89, 5.47, and 13.95%). Illicit opioid use was associated with increased frequency of moderate/major clinical effects (54.2 vs. 27.4%), need for an ICU procedure (11.4 vs. 6.8%), and death (3.9 vs. 1.2%) compared with prescription opioid use. Suicidal intent (34.88%) followed by misuse/abuse (26.26%) were the most frequent intents. Misuse/abuse increased in frequency over each epoch in the study period (23.1 vs. 26.12 vs. 30.3%). Discussion and conclusions: The severity of clinical effects and death following acute opioid poisonings increased over the study period, driven by suicidal intent and an increasing proportion of illicit opioid cases. This study highlights the importance of developing strategies to address suicide prevention in addition to the continued focus on opioid use disorder.

Objective: To investigate the role of insurance carriers and changes in insurance on rates of cancelation and rescheduling of tympanostomy tube surgery., Methods: Retrospective cohort study between January 1, 2013 and December 31, 2018 at a single tertiary care academic pediatric otolaryngology practice of pediatric patients (≤18 years) who underwent tympanostomy tube placement for any indication. Patients had to have insurance providers recorded both at clinic visit and at the time of surgery. Rates of cancelation and postponement of tympanostomy tube placement were assessed. Logistic regression was performed to determine factors associated with cancelation or postponement of surgery., Results: Of the 5080 patients, 2961 patients had Medicaid and 2012 patients had private insurance at the time of surgery. A total of 197 (3.96%) patients switched insurance between clinic appointment and date of surgery. Time to surgery was nearly 2 weeks more for those who had a change in insurance vs. those who did not (33 vs. 20 days, P  < .001). Those who switched insurance were nearly twice as likely to have to reschedule surgery than those who did not (OR 1.95, CI 1.42-2.67). Patients who had Medicaid as the primary payer also had increased odds of needing to reschedule and postpone surgery (OR 1.39, 95% CI 1.17-1.63)., Conclusion: Difference in insurance carrier and loss/change of insurance appear to be associated with delays in tympanostomy tube placement. Standardization of re-enrollment schedules across insurance providers or a single payer model may be useful in addressing these delays in care.

Background: The cumulative (dis)advantage (CAD) perspective more and more is examined in a comparative way, to highlight the role of context in generating inequality over the life course. This study adds to this field of research by examining trajectories of activities of daily living (ADL) in later life by educational level in a country comparison of England and Germany, emphasizing differing institutional conditions., Method: Data used are the English Longitudinal Study of Ageing (ELSA; 11,352 individuals) and the German subsample of the Survey of Health and Retirement in Europe (SHARE; 5,573 individuals). Using population averaged Poisson panel regression models, 12-year trajectories of six birth cohorts are investigated, covering the age range of 50 to 90 years., Results: Respondents in England have a higher level of limitations at age 50, and more limited increases over age than in Germany. An educational gradient exists in both countries at age 50. Notably, the educational gradient increases for more recently born cohorts, but declines with increasing age in England, while in Germany educational differences increase for more recently born cohort only., Discussion: The current study indicates that CAD processes between educational groups are context sensitive. While England showed convergence of disparities with increasing age, in Germany no differential development was found., Competing Interests: The authors have declared that no competing interests exist.

Objective: Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) can be associated with significant blood loss. It has been suggested that blood loss is greater in different racial groups. The purpose of this study was to evaluate differences in blood loss between African American and Caucasian patients undergoing PSF for AIS., Methods: A retrospective review was performed of patients aged 10-18 years with AIS who were treated with PSF from 2014 to 2017 at a single children's healthcare system. Patient demographic, radiographic, and operative data were obtained from medical records. Intraoperative blood loss was calculated using the formula described by Waters et al. Patients who declined reporting their race or had prior spinal surgery, neuromuscular or syndromic diagnoses, a history of cardiac or thoracic surgery, or a bleeding disorder were excluded. Blood loss variables were log-transformed for normality and modeled using multivariable linear regression., Results: A total of 433 PSFs for AIS qualified for the analysis. The average age was 14.1 years, and 73.7% of the patients were female. With respect to race, 44.6% identified themselves as African American. There was no significant difference in blood loss (p = 0.31) or blood loss per level fused (p = 0.36) in African American patients. African American patients, however, did have significantly lower preoperative hemoglobin and hematocrit levels and greater operating room time than Caucasian patients (p < 0.001). There was no difference between race and transfusion rate., Conclusions: There appears to be no relationship between race and blood loss during PSF for AIS. Standardized protocols for minimizing perioperative blood loss can be applied to both Caucasian and African American patients.

Background: Polymerase chain reaction (PCR) respiratory viral panel (RVP) testing is often used in evaluation of pediatric cancer patients with febrile neutropenia (FN), but correlation with adverse outcomes has not been well characterized., Procedure: A retrospective cohort of all children ages 0-21 years with cancer admitted to Children's Healthcare of Atlanta for FN from January 2013 to June 2016 was identified. Patient demographic and clinical variables such as age, RVP results, length of stay (LOS), and deaths were abstracted. Relationship between RVP testing and positivity and LOS, highest temperature (Tmax), hypotension and intensive care unit (ICU) admission were compared using Wilcoxon rank sums, chi-square, or Fisher's exact tests adjusting for age, sex, bacteremia, and diagnosis., Results: The 404 patients identified had 787 total FN admissions. RVPs were sent in 38% of admissions and were positive in 59%. Patients with RVPs sent were younger (median 5.5 vs 8.0 years, P < .0001) with higher Tmax (39.2° vs 39.1°, P = .016). The most common virus identified was rhinovirus/Enterovirus (61%). There were no significant differences in highest temperature or lowest blood pressure based on RVP positivity. Patients admitted to the ICU were more likely to have RVPs sent (odds ratio [OR] = 3.19, P < .002); however, neither having RVP testing nor RVP positivity were significantly associated with increased LOS or death. Coinfection with bacteremia and a respiratory virus was identified in 9.1% of patients., Conclusions: These data raise the question of the utility of sending potentially costly RVP testing as RVP positivity during febrile neutropenia does not impact LOS, degree of hypotension, or ICU admission., (© 2020 Wiley Periodicals LLC.)

Background/purpose: To assess trends and resource use attributable to firearm-related injuries in US pediatric intensive care units (PICUs)., Methods: Retrospective data from Pediatric Health Information Systems (PHIS) database from 2004 to 2017., Results: Of 5,984,938 admissions to 28 children's hospitals, 3707 were for firearm injuries. A total of 1088 of 3707 hospitalizations (29.9%) required PICU admission. Median PICU length of stay was 2 days (IQR, 1-6 days), and the median cost for PICU patients was $37,569.31 (IQR, $19,243.83-$77,856.32). Use of mechanical ventilation (674/1088 admissions [61.9%]), surgical procedures (744/1088 admissions [68.3%]), blood transfusions (429/1088 admissions [39.9%]), and intracranial pressure monitoring devices (30/1088 admissions [2.8%]) increased in PICU patients. Computed tomography showed an overall increase (197/287 [68.6%] to 138/177 [78%], P = .037) from 2004 to 2007 to 2016-2017. Mortality among PICU patients (140/1058 [13.23%]) attributable to firearm-related injuries increased insignificantly (34/285 (11.93%] to 25/172 [14.53%], P = .746)., Conclusions: Using PHIS data, we found a significant increase in median cost per hospitalization and an increase in critical care resource use, including the frequency of invasive mechanical ventilatory assistance, neuromonitoring, operations performed, and transfusion of blood products. Further research is needed to continue to characterize the burden of pediatric critical firearm injury., Type of Study: Retrospective cohort study., Level of Evidence: Level III., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: One of the most pervasive complications of burn injury is wound progression, characterized by continuous tissue destruction in untreated wounds, which leads to wound infection, inflammation, oxidative stress and excessive scar formation. We determined whether additional tissue destruction could be attenuated with Livionex formulation (LF) lotion, which contains a metal-chelating agent and reduces inflammation in burn wounds., Methods: We subjected male Sprague Dawley rats to a 2% total body surface area (TBSA) burn using a brass comb model and topically applied LF lotion (containing ethylenediaminetetraacetic acid and methyl sulfonyl methane) to the affected area every 8 hours over 3 days. Inflammatory cytokine levels, cell apoptosis and wound healing were compared in LF lotion-treated and untreated rats. Statistical analysis was performed using a one-way analysis of variance in conjunction with Tukey's post-hoc test., Results: Serum inflammatory cytokines were not detectable after 3 days, suggesting that small burn wounds induce only an immediate, localized inflammatory response. Microscopy revealed that LF lotion improved burn site pathology. Deoxynucleotidyl transferase biotin-d-UTP nick-end labeling staining showed reduced cell death in the LF-treated samples. LF lotion prevented the spread of tissue damage, as seen by increased amounts of Ki-67-positive nuclei in the adjacent epidermis and hair follicles. Tumor necrosis factor-alpha, interleukin-6 and inducible nitric oxide synthase levels in LF-treated skin sections from burned rats were comparable to the levels observed in unburned control sections, indicating that LF lotion reduces inflammation in and around the burn site., Conclusions: These results establish LF lotion as a therapeutic agent for reducing inflammatory stress, cell death and tissue destruction when applied immediately after a burn injury. Further studies of LF lotion on large TBSA burns will determine its efficacy as an emergency treatment for reducing long-term morbidity and scarring., (© The Author(s) 2020. Published by Oxford University Press.)

Background: The Centers for Disease Control and Prevention (CDC) recommend universal human immunodeficiency virus (HIV) screening starting at 13 years, which has been implemented in many general U.S. emergency departments (EDs) but infrequently in pediatric EDs. We aimed to 1) implement a pilot of routine adolescent HIV screening in a pediatric ED and 2) determine the unique barriers to CDC-recommended screening in this region of high HIV prevalence., Methods: This was a prospective 4-month implementation of a routine HIV screening pilot in a convenience sample of adolescents 13 to 18 years at a single pediatric ED, based on study personnel availability. Serum-based fourth-generation HIV testing was run through a central laboratory. Parents were allowed to remain in the room for HIV counseling and testing. Data were collected regarding patient characteristics and HIV testing quality metrics. Comparisons were made using chi-square and Fisher's exact tests. Regression analysis was performed to assess for an association between parent presence at the time of enrollment and adolescent decision to participate in HIV screening., Results: Over 4 months, 344 of 806 adolescents approached consented to HIV screening (57% female, mean ± SD = 15.1 ± 1.6 years). Adolescents with HIV screening were more likely to be older than those who declined (p = 0.025). Other blood tests were collected with the HIV sample for 21% of adolescents; mean time to result was 105 minutes (interquartile range = 69 to 123) and 79% were discharged before the result was available. Having a parent present for enrollment was not associated with adolescent participation (adjusted odds ratio = 1.07, 95% CI = 0.67 to 1.70). Barriers to testing included: fear of needlestick, time to results, cost, and staff availability. One of 344 tests was positive in a young adolescent with Stage 1 HIV., Conclusions: Routine HIV screening in adolescents was able to be implemented in this pediatric ED and led to the identification of early infection in a young adolescent who would have otherwise been undetected at this stage of disease. Addressing the unique barriers to adolescent HIV screening is critical in high-prevalence regions and may lead to earlier diagnosis and treatment in this vulnerable population., (© 2020 by the Society for Academic Emergency Medicine.)

Top-down mass spectrometry (MS)-based proteomics enable a comprehensive analysis of proteoforms with molecular specificity to achieve a proteome-wide understanding of protein functions. However, the lack of a universal software for top-down proteomics is becoming increasingly recognized as a major barrier, especially for newcomers. Here, we have developed MASH Explorer, a universal, comprehensive, and user-friendly software environment for top-down proteomics. MASH Explorer integrates multiple spectral deconvolution and database search algorithms into a single, universal platform which can process top-down proteomics data from various vendor formats, for the first time. It addresses the urgent need in the rapidly growing top-down proteomics community and is freely available to all users worldwide. With the critical need and tremendous support from the community, we envision that this MASH Explorer software package will play an integral role in advancing top-down proteomics to realize its full potential for biomedical research.

Introduction: Previous studies using administrative data have demonstrated that the United States opioid epidemic is harming both adults and children, and is straining health care systems. Our objective is to describe the outcomes and trends in resource use among children with acute opioid ingestions using patient-level case report data. Materials and Methods: This study was a retrospective analysis of prospectively collected data from the 55 poison control centers in the United States which comprise the National Poison Data System (NPDS). Children under 19 years of age with a primary opioid ingestion between 1 January 2005 and 31 December 2018 were included in the analysis. Trends over three eras (2005-2009, 2010-2014, 2015-2018) were assessed using a Cochran-Armitage Trend Test. Yearly trends in the proportion of cases were calculated using generalized linear models. Multi-variable logistic regression analysis was used to calculate the adjusted odds of variables associated with having at least one Pediatric Intensive Care Unit (PICU) level intervention. Results: Children were involved in 207,543 (27.54%) of a total of 1,002,947 primary exposure-related opioid poisoning cases reported to US poison centers. The percentage of patients admitted to a critical care unit from these exposures increased in each era (6.6%, 8.5%, 9.6%). Suicidal intent increased in each era (14.0%, 15.3%, 21.2%), and was associated with increased adjusted odds of receiving a PICU procedure (OR 9.68, CI 7.97-11.76). Fentanyl (OR 12, CI 9.2-15.7), heroin (OR 11.1, CI 9.4-13.1), and methadone (OR 15, CI 13-17.3) were the opioids most associated with having a PICU procedure. Discussion and Conclusions: The severity of admissions for acute opioid ingestions, especially following attempted suicide, has increased over the studied time frame. Efforts focused on reducing access, especially to synthetic and illicit opioids, and addressing adolescent suicidality are needed to reduce these serious consequences of the opioid epidemic on children in the United States.

Background: Various measures and definitions for undernutrition are used in pediatrics. Younger children treated for cancer are at high risk, but lack well-defined risk-based screening and intervention., Methods: A retrospective study collected weight longitudinally for patients less than three years-old over two years after initiating cancer treatment. We included those diagnosed 2007-2015 at a large pediatric cancer center. Exclusion criteria included treatment starting outside our system, secondary or relapsed malignancy, or incomplete information. A decrease ≥1 in weight-for-age or weight-for-height z-score signified clinically significant weight loss. Univariate and multivariate models assessed hazards for developing first episode of clinically significant weight loss., Results: Of 372 patients, only 24.6% of patients lost 10% of weight, but 58.6% lost weight-for-age z-score ≥1 and 64.8% lost ≥1 weight-for-height z-score within two years of treatment initiation. Patients who lost weight were younger (median age 15 vs. 24 months, p < 0.001). Compared to patients diagnosed in the first year of life, those diagnosed 24-35 months were less likely to lose weight (HR 0.62, p < 0.001) and lost weight later (median time to weight loss 144 vs. 35 days). Higher treatment intensity increased weight loss risk (HR 2.30, p < 0.001) and decreased time to weight loss (35 vs. 154 days). No differences were found based on sex, diagnosis, enteral or parenteral nutrition, gastroenterology consults, or intensive care admissions., Conclusions: Using normalized z-scores is more sensitive for identifying weight loss. Younger children are more likely to lose weight with higher intensity cancer therapy. Patient and treatment specific information should be used in risk stratifying weight loss screening and nutritional interventions., Competing Interests: Declaration of Competing Interest The authors do not have a financial relationship with the organizations sponsoring this research that would create a real or perceived conflict of interest. The corresponding author has full control and ownership of the data presented here and can be produced for review by the journal if requested., (Copyright © 2020 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Geochemical processes change the microstructure of rocks and thereby affect their physical behaviour at the macro scale. A micro-computer tomography (micro-CT) scan of a typical reservoir sandstone is used to numerically examine the impact of three spatial alteration patterns on pore morphology, permeability and elastic moduli by correlating precipitation with the local flow velocity magnitude. The results demonstrate that the location of mineral growth strongly affects the permeability decrease with variations by up to four orders in magnitude. Precipitation in regions of high flow velocities is characterised by a predominant clogging of pore throats and a drastic permeability reduction, which can be roughly described by the power law relation with an exponent of 20. A continuous alteration of the pore structure by uniform mineral growth reduces the permeability comparable to the power law with an exponent of four or the Kozeny-Carman relation. Preferential precipitation in regions of low flow velocities predominantly affects smaller throats and pores with a minor impact on the flow regime, where the permeability decrease is considerably below that calculated by the power law with an exponent of two. Despite their complete distinctive impact on hydraulics, the spatial precipitation patterns only slightly affect the increase in elastic rock properties with differences by up to 6.3% between the investigated scenarios. Hence, an adequate characterisation of the spatial precipitation pattern is crucial to quantify changes in hydraulic rock properties, whereas the present study shows that its impact on elastic rock parameters is limited. The calculated relations between porosity and permeability, as well as elastic moduli can be applied for upscaling micro-scale findings to reservoir-scale models to improve their predictive capabilities, what is of paramount importance for a sustainable utilisation of the geological subsurface.

Purpose: To improve opioid stewardship for umbilical hernia repair in children., Methods: An educational intervention was conducted at 9 centers with 79 surgeons. The intervention highlighted the importance of opioid stewardship, demonstrated practice variation, provided prescribing guidelines, encouraged non-opioid analgesics, and encouraged limiting doses/strength if opioids were prescribed. Three to six months of pre-intervention and 3 months of post-intervention prescribing practices for umbilical hernia repair were compared., Results: A total of 343 patients were identified in the pre-intervention cohort and 346 in the post-intervention cohort. The percent of patients receiving opioids at discharge decreased from 75.8% pre-intervention to 44.6% (p < 0.001) post-intervention. After adjusting for age, sex, umbilicoplasty, and hospital site, the odds ratio for opioid prescribing in the post- versus the pre-intervention period was 0.27 (95% CI = 0.18-0.39, p < 0.001). Among patients receiving opioids, the number of doses prescribed decreased after the intervention (adjusted mean 14.3 to 10.4, p < 0.001). However, the morphine equivalents/kg/dose did not significantly decrease (adjusted mean 0.14 to 0.13, p = 0.20). There were no differences in returns to emergency departments or hospital readmissions between the pre- and post-intervention cohorts., Conclusions: Opioid stewardship can be improved after pediatric umbilical hernia repair using a low-fidelity educational intervention., Type of Study: Retrospective cohort study., Level of Evidence: Level II., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Top-down mass spectrometry (MS) is a powerful tool for the identification and comprehensive characterization of proteoforms arising from alternative splicing, sequence variation, and post-translational modifications. However, the complex data set generated from top-down MS experiments requires multiple sequential data processing steps to successfully interpret the data for identifying and characterizing proteoforms. One critical step is the deconvolution of the complex isotopic distribution that arises from naturally occurring isotopes. Multiple algorithms are currently available to deconvolute top-down mass spectra, resulting in different deconvoluted peak lists with varied accuracy compared to true positive annotations. In this study, we have designed a machine learning strategy that can process and combine the peak lists from different deconvolution results. By optimizing clustering results, deconvolution results from THRASH, TopFD, MS-Deconv, and SNAP algorithms were combined into consensus peak lists at various thresholds using either a simple voting ensemble method or a random forest machine learning algorithm. For the random forest algorithm, which had better predictive performance, the consensus peak lists on average could achieve a recall value (true positive rate) of 0.60 and a precision value (positive predictive value) of 0.78. It outperforms the single best algorithm, which achieved a recall value of only 0.47 and a precision value of 0.58. This machine learning strategy enhanced the accuracy and confidence in protein identification during database searches by accelerating the detection of true positive peaks while filtering out false positive peaks. Thus, this method shows promise in enhancing proteoform identification and characterization for high-throughput data analysis in top-down proteomics.

Objective: Pediatric oncology nurses can experience burnout, vicarious traumatization, and compassion fatigue related to the unique stressors of their profession. Opportunities to enhance nurses' professional commitment and nurse-patient connectedness may mitigate these stressors. This study explored the impact of volunteering at a local oncology camp on pediatric oncology nurses' professional quality of life and connectedness with their oncology patients. Method and Sample: Pediatric oncology nurses from a single institution were invited to participate in this mixed methods study. Participants completed a survey assessing professional quality of life, professional commitment, and patient connectedness. Nurses who had oncology camp volunteer experience were invited to participate in a qualitative interview. Results: Compared with noncamp nurses ( n = 23), camp nurses ( n = 25) had increased odds of a low burnout score (odds ratio = 6.74, 95% confidence interval [1.10, 41.43], p = .039) and increased odds of a high compassion satisfaction score (odds ratio = 4.69, 95% confidence interval [1.14, 19.32], p = .033). Qualitative interviews supported the impact of volunteering at camp on nurses' personal and professional perspective, nursing practice, and delivery of person-centered care. Conclusion: Volunteering at a pediatric oncology camp provided nurses the opportunity to engage with patients, share experiences, and view patients as individuals while still maintaining professional boundaries. Nurses who volunteer at camp described a perspective moving beyond patient-centered to person-centered care, and for some pediatric oncology nurses, camp volunteering may be a novel way to mitigate burnout and an important tool to enhance resiliency.

Toll-like receptors (TLRs) belong to pattern recognition receptors, which respond to danger signals such as pathogen-associated molecular patterns or damage-associated molecular patterns. Upon TLR activation in microglia, the major immune cells in the brain, distinct signaling cascades trigger the production of inflammatory molecules, being a critical feature in neuroinflammation and neurodegenerative processes. Recently, individual microRNAs (miRNAs) were shown to act as endogenous TLR ligands. Here, we conducted systematic screening for miRNAs as potential TLR7/8 ligands by small RNA sequencing of apoptotic neurons and their corresponding supernatants. Several miRNA species were identified in both supernatants and injured neurons, and 83.3% of the media-enriched miRNAs activated murine and/or human TLR7/8 expressed in HEK293-derived TLR reporter cells. Among the detected extracellular miRNAs, distinct miRNAs such as miR-340-3p and miR-132-5p induced cytokine and chemokine release from microglia and triggered neurotoxicity in vitro. Taken together, our systematic study establishes miRNAs released from injured neurons as new TLR7/8 activators, which contribute to inflammatory and neurodegenerative responses in the central nervous system (CNS).

Background: Health care disparities in Appalachia are well documented. However, no previous studies have examined possible differences in the utilization of breast reconstruction (BR) in Appalachia. This study aims to determine if a disparity in BR utilization exists in women from Appalachia Kentucky., Methods: A retrospective, population-based cohort study was conducted from January 1, 2006, to December 31, 2015. The Kentucky Cancer Registry was queried to identify population-level data for female patients diagnosed with breast cancer and treated with mastectomy. A multivariate logistic regression model controlling for patient, disease, and treatment characteristics was constructed to predict the likelihood of BR., Results: Bivariate testing showed differences (P < 0.0001) in BR utilization between Appalachian and non-Appalachian women in Kentucky (15.0% and 26.3%, respectively). Multivariate analysis showed that women from Appalachia (odds ratio, 0.54; confidence interval (95), 0.48-0.61; P < 0.0001) were less likely to undergo BR than non-Appalachian women. Interestingly, the rate of BR increased over time in both Appalachian (r = 0.115; P < 0.0001) and non-Appalachian women (r = 0.148; P < 0.0001)., Conclusions: Despite the benefits of BR, women from Appalachia undergo BR at lower rates and are less likely to receive BR than non-Appalachian Kentuckians. Although the rates of BR increased over time in both populations, access to comprehensive breast cancer care remains a challenge for women from Kentucky's Appalachian region.

Background & Aims: Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD., Methods: We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234 adults without the Pi*Z mutation (controls), all without pre-existing liver disease. We collected data on demographic parameters, comorbidities, lung- and liver-related health, and blood samples for laboratory analysis. Liver fibrosis was assessed non-invasively via the serum tests Aspartate Aminotransferase to Platelet Ratio Index and HepaScore and via transient elastography. Liver steatosis was determined via transient elastography-based controlled attenuation parameter. We performed histologic analyses of livers from transgenic mice that overexpress the AATD-associated Pi*Z variant., Results: Serum levels of liver enzymes were significantly higher in Pi*ZZ carriers vs controls. Based on non-invasive tests for liver fibrosis, significant fibrosis was suspected in 20%-36% of Pi*ZZ carriers, whereas signs of advanced fibrosis were 9- to 20-fold more common in Pi*ZZ carriers compared to non-carriers. Male sex; age older than 50 years; increased levels of alanine aminotransferase, aspartate aminotransferase, or γ-glutamyl transferase; and low numbers of platelets were associated with higher liver fibrosis burden. We did not find evidence for a relationship between lung function and liver fibrosis. Controlled attenuation parameter ≥280 dB/m, suggesting severe steatosis, was detected in 39% of Pi*ZZ carriers vs 31% of controls. Carriers of Pi*ZZ had lower serum concentrations of triglyceride and low- and very-low-density lipoprotein cholesterol than controls, suggesting impaired hepatic secretion of lipid. Livers from Pi*Z-overexpressing mice had steatosis and down-regulation of genes involved in lipid secretion., Conclusions: In studies of AATD adults with the Pi*ZZ mutation, and of Pi*Z-overexpressing mice, we found evidence of liver steatosis and impaired lipid secretion. We identified factors associated with significant liver fibrosis in patients, which could facilitate hepatologic assessment and counseling of individuals who carry the Pi*ZZ mutation. ClinicalTrials.gov Number NCT02929940., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Direct comparison studies of outcomes and aesthetic satisfaction of anatomic implants compared to other implants are scarce in the literature., Objectives: The objective of this study was to compare outcomes and aesthetic satisfaction of patients who underwent breast reconstruction with anatomic implants vs other implants (smooth round silicone)., Methods: A retrospective chart review was performed of patients who underwent implant-based breast reconstruction over 3 years. Outcomes including complications, number of surgeries, need for revisions, and aesthetic satisfaction of patients were tracked and compared., Results: A total of 156 patients met inclusion criteria for this study. A total of 123 underwent reconstruction with a round implant, and 33 underwent reconstruction with an anatomic implant. Of the 156 patients, 38 underwent a 1-stage direct-to-implant reconstruction and the remainder underwent a 2-stage implant reconstruction. The round and anatomic implant groups did not differ with regards to number of surgeries, revisions, utilization of contralateral symmetry procedures, implant-related reoperations, complications, implant loss, infection, capsular contracture, and seroma. The Breast Q survey had a response rate of 27%. On all parameters, the round and anatomic implant groups did not significantly differ., Conclusions: There were no significant differences among round and shaped implants in regards to complications, revision surgeries, and overall outcomes. Furthermore, patients showed no differences regarding satisfaction and well-being when surveyed on the Breast Q survey. The decision of implant choice in breast reconstruction should be based on surgeon comfort and the patient's needs/body type., Level of Evidence: 4., (© 2019 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Background: Intimate partner violence (IPV) is associated with adverse health effects and increased healthcare utilization. Systems-level interventions have been shown to be effective in identifying and referring survivors but little is known about how these strategies impact future utilization. The objective of this study is to examine the impact of a systems-level response on healthcare utilization among patients screening positive for IPV from November 2016 to February 2019 in a large multi-specialty outpatient health system in the Midwest., Methods: Using electronic health record (EHR) data, we identified patients who screened positive for IPV (N = 756) and categorized their response as accepted printed material (N = 116), accepted direct referrals (N = 85), declined both (N = 271), or missing (N = 255). We used negative binomial models to model post-period utilization as a function of decision group, pre-period utilization, and clinical and demographic factors., Results: After controlling for demographic characteristics and baseline utilization, the printed materials and direct referral groups had higher utilization rates than those who declined printed materials and direct referral during the post-period for every type of service. However, these differences were only statistically significant for outpatient, behavioral health, and social work services. Specifically, the visit rate for patients receiving printed materials was two times higher (rate ratio: 2.18; 95% CI: 1.21, 3.94) for behavioral health services and three times higher (rate ratio: 3.33; 95% CI: 1.3, 8.52) for social work services compared to those who refused printed material and direct referral. For those opting for a direct referral, the visit rate was two times higher for outpatient services (rate ratio: 1.97; 95% CI: 1.13, 3.42) compared to those who refused., Conclusions: Patients receiving printed materials or direct referrals had more social work and behavioral health visits, highlighting an important outcome of the protocol. However, higher utilization rates among outpatient services and a trend toward higher utilization of other services, including the emergency department, suggest greater health service utilization is not diminished by the systems level response-at least not within a two-year time frame.

Background: A previously implemented Enhanced Recovery Protocol (ERP) for children undergoing elective gastrointestinal operations demonstrated decreased length of stay (LOS) and in-hospital opioid use. We hypothesized that the ERP would be associated with decreased postdischarge opioid prescribing., Methods: Demographic, operative, and opioid prescription data were retrospectively compared between elective gastrointestinal surgical patients in the pre-ERP (1/2012-12/2014) and the post-ERP periods (1/2015-12/2017)., Results: Of the 99 patients reviewed, 56 (56.7%) were treated in the post-ERP era. Overall, 48 (48.5%) were male, and the most common operation was partial or total colectomy (n = 39, 39.4%) followed by ileocecectomy (n = 26, 26.3%). Most patients were 15-16 years of age and had inflammatory bowel disease (n = 88, 88.9%). LOS decreased from a median 4 days pre-ERP to 3 days post-ERP (p = 0.02). Patients receiving intraoperative opioids decreased from 100% to 46% (p < 0.01) and postoperative opioids from 95% to 59% (p < 0.01). Patients receiving an opioid prescription at discharge decreased from 69.8% pre-ERP to 30.9% post-ERP (p < 0.01). Among patients prescribed opioids at discharge, the number of doses (median 23 to 17, p = 0.44) and the median morphine equivalents/kg remained stable (median 2.3 to 1.7, p = 0.10)., Conclusions: A pediatric gastrointestinal surgery ERP resulted in decreased postdischarge prescribing of opioids., Type of Study: Retrospective cohort study., Level of Evidence: Level II., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Well-being in retirement is thought to depend on person's level of resources and how his or her resources change during retirement. However, to date few studies have directly investigated resource trajectories during retirement. The current study therefore examines how economic, personal, and social-relational resources change during the retirement transition for people retiring from paid employment and for people retiring from other, non-working labour market statuses (e.g. disability pension, homemaker, unemployment). Based on four representative baseline samples of the German Ageing Survey (1996, 2002, 2008, and 2014) and their respective 6-year follow-up interviews, we identified N  = 586 retirees. We then used dual change score models to separately estimate the level and change in income, health, activity, family and non-family network size, and social support for people retiring from paid work ( n  = 384) and people retiring from other statuses ( n  = 202) adjusted for age, gender, education, region, period, and time since retirement. Overall, we found that resources changed only modestly during the retirement transition. Resource changes did, however, differ by last labour market status and sociodemographic characteristics. Income and social support declined and family networks increased for both those retiring from paid work and those retiring from other statuses. Leisure activities increased only for those retiring from paid work. No changes in health or non-family networks were observed. People with many resources before retirement also had many resources after retirement. We conclude that retirement affects resources less than researchers often expect. Accordingly, differences based on labour market remain despite retirement., (© Springer Nature B.V. 2019.)

Objective: Dermal invasion is characteristic of more aggressive basal cell carcinoma (BCC) tumors. However, reporting the depth of invasion of BCC is not currently a standard or recommended practice. The purpose of this study was to document the depth of invasion of BCC. Design: Original hematoxylin and eosin-stained slides of biopsied BCCs (N=500) were reviewed. The depth of invasion was measured for each case. Each case was also determined to be aggressive or nonaggressive based on the presence of additional histologic features. Setting: Biopsy specimens from a large private practice were reviewed. Measurements: Descriptive statistics were calculated for all cases. To compare the average depth of invasion of cases with aggressive features versus cases with nonaggressive features, two-tailed, independent t-tests were computed. Results: The overall median depth of invasion was 0.68mm (range: 0.10-5.49). The median depth of invasion of aggressive cases (n=68) was 1.04mm, while the median depth of invasion of nonaggressive cases (n=432) was 0.62mm. The difference between median depth of invasion of aggressive and nonaggressive cases was found to be significant ( p <0.0001). This significant difference ( p <0.0001) was maintained even with transection, which was present in the majority of cases (n=347; 69.4%). Conclusions: Dermal invasion depths of all subtypes of BCC have not been previously reported. The median dermal invasion of histologically aggressive BCC is greater than nonaggressive tumors. These findings might help clinicians in determining the depth of biopsy and choice of treatment., Competing Interests: FUNDING:No funding was received for this study. DISCLOSURES:The authors have no conflicts of interest relevant to the content of this article.

We examine the association between pathways to retirement and patterns of subjective well-being in Germany. We argue that short-term development of subjective well-being is related to social status changes while long-term development of subjective well-being is related to resources and changes in life circumstances. Importantly, we expect that how a person's social status changes and his/her access to resources post-retirement both depend on the person's specific pathway to retirement, resulting in distinct patterns of subjective well-being post-retirement. Based on data from the German Socio-Economic Panel, we categorized people as retiring from employment, short- or long-term unemployment, labour market inactivity or due to disability. We then used dual-change score models to compare trajectories of life satisfaction ten years before to ten years after the retirement transition. For people retiring from employment, life satisfaction did not change in the short term but developed more positively in the long term. In comparison, people retiring from unemployment or due to disability experienced a short-term increase in life satisfaction but had more negative long-term trajectories of life satisfaction. We found no retirement-related changes in life satisfaction for people retiring from inactivity. The findings suggest that different pathways to retirement are related to distinct patterns of subjective well-being and highlight the importance of late-life employment biographies for quality of life post-retirement., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It has been previously shown that anesthesia and analgesia can affect outcomes in the rat burn model and that buprenorphine alleviated pain without drastically altering the outcomes of interest. Recently, the use of a sustained release (SR) formulation of buprenorphine has been promoted over conventional buprenorphine. In this study, we assessed whether buprenorphine-SR altered hemodynamic parameters in our rat model of severe burn injury., Materials and Methods: Adult male Sprague-Dawley rats were randomized to receive either conventional buprenorphine (0.05 mg/kg) or buprenorphine-SR (1 mg/kg). Buprenorphine-SR was administered 24 h before the experiment. Buprenorphine was administered on the day of experiment. These groups were further randomized to control or scald burn (60% of total body surface area). Systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) were measured using a noninvasive blood pressure system before receiving analgesia and after 72 h., Results: As expected, HR was significantly higher after burn injury regardless of analgesic (P <0.0001). Both SBP and DBP were significantly decreased in burned animals receiving conventional buprenorphine (P < 0.0001), but neither was altered in the buprenorphine-SR-treated burned animals. However, SBP, DBP, and HR were significantly increased after 72 h in control animals receiving buprenorphine-SR (P < 0.0001)., Conclusions: These data indicate that buprenorphine-SR alters the hemodynamic response to injury and may not be an appropriate choice for a model of severe burn injury. If this analgesic is used, investigators must cautiously form conclusions, especially in experimental conditions that would be expected to alter cardiac hemodynamics., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Importance: Over the past 20 years, opioid misuse and opioid addiction have risen to epidemic proportions in the United States. One-third of adults receiving long-term opioid therapy report that their first opioid prescription came from a surgeon, indicating that postsurgical prescribing is an important point of intervention in the opioid epidemic. Such interventions differ from historical interventions on prescribing in that they must be closely monitored to ensure pain continues to be adequately controlled after surgical procedures. As evidence on nonopioid-based pain control grows, a key question is how to implement practice change in postsurgical discharge prescribing., Objective: To examine interventions associated with changing opioid prescription practices on surgical discharge., Evidence Review: Studies published after 2000 that included interventions that aimed at postsurgical opiate stewardship and evaluated outcomes were included. PubMed and Embase were searched through March 2018 for relevant articles, with additional articles retrieved based on citations in articles retrieved in the initial search. Quality was assessed by 2 independent reviewers using the Quality Assessment Tool for Quantitative Studies, and quality scores were reconciled through discussion and mutual agreement., Findings: Eight studies met inclusion criteria, of which 3 were preintervention and postintervention comparison studies, 3 were controlled clinical studies, 1 was a time-series study, and 1 compared postintervention results with a predetermined baseline. Interventions done at the organization level, including changes to electronic health records order sets and workflow, showed clear positive results. Additionally, 2 studies that centered on developing guidelines based on actual patient opioid use and disseminating these guidelines to clinicians reported reductions up to 53% in the quantity prescribed. No increases in emergency department visits or refill requests were reported in studies measuring these outcomes. However, 1 study focused on reducing the number of children who were prescribed codeine found via check-in telephone calls that 13 of 240 patients (5.4%) had inadequately controlled pain., Conclusions and Relevance: The studies reviewed provide evidence that clinician-mediated and organizational-level interventions are powerful tools in creating change in postsurgical opioid prescribing. This summary highlights paucity of high-quality studies that provide clear evidence on the most effective intervention at reducing postoperative opioid prescribing.

Introduction: A newly developed total implant telemetry system for cardiovascular (CV), electrophysiological and body temperature measurement was evaluated. A cloud-based transmission of the physiological signals allowed an assessment of the quality of the physiological signals despite the physical separation between the instrumented animals and the evaluating home laboratory. The new system is intended to be used for safety pharmacological evaluations of drug candidates in various species., Methods: Two female minipigs, 6 Labrador-mixed breed dogs and 4 female Cynomolgus monkeys were instrumented with a newly developed total implant system (TSE SYSTEMS). The implants feature a microprocessor, internal memory (1 GB), 2 solid state pressure-tipped catheters, amplifiers and a radio transmitter. Sampling rates for each measurement can be selected within a range between 0.1 and 1 kHz. Biological signals are selected in a programmable fashion on a session-by-session basis according to a user-defined protocol. The pressure sensors are at the tip of an electrical lead having a length customized to each species. Core temperature measurement and activity monitoring (3D accelerometer) are included in the system. Digital transmission range using a single antenna is 5 m with up to 16 animals held together and monitored simultaneously. The range can be expanded with more antennas in an array coupled to a single receiver. The antenna/receiver station consists of a single USB powered mobile unit connected to a PC or laptop. The battery life provides 110 days of continuous recording. The dogs and minipigs were instrumented and monitored in Germany. A novel cloud-based data transmission system was developed to monitor the physiological signals in real-time from the Cynomolgus monkeys, still kept in Mauritius, from the data evaluation laboratory in Germany. After recovery from the surgical implantation, aortic pressure (AP), left ventricular pressure (LVP), ECG and body temperature were recorded for 24 hr monitoring sessions in all animals. Additionally, moxifloxacin (10, 30 and 100 mg/kg) was tested in the dog model using a modified Latin square cross-over study design., Results: The implant was well tolerated and the animals recovered rapidly from the implantation procedure. Excellent signal quality was obtained and stable hemodynamic and electrophysiological parameters could be measured, with little signal artefact or drop-out, over 24 h in each species. After oral dosing of moxifloxacin to the dogs, a substantial, dose-dependent increase in the QT-interval duration could be shown, as anticipated for this agent. Cloud-based data acquisition from the animals in Mauritius and the data evaluation lab in Germany worked well., Conclusion: This new CV telemetry system provides a novel alternative to fluid-filled catheter telemetry systems and the coupling to a cloud-based data transmission allows for flexibility in the location of the instrumented animals and data acquisition and the location of the site for data analysis. For the first time it is technically feasible to conduct a CV safety pharmacology study in Cynomolgus monkeys without having to ship them long distances to the home laboratory., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Although it has been known for decades that patients with alpha1-antitrypsin deficiency (AATD) have an increased risk of cirrhosis and hepatocellular carcinoma, limited data exist on non-invasive imaging-based methods for assessing liver fibrosis such as magnetic resonance elastography (MRE) and acoustic radiation force impulse (ARFI) quantification, and no data exist on 2D-shear wave elastography (2D-SWE). Therefore, the purpose of this study is to evaluate and compare the applicability of different elastography methods for the assessment of AATD-related liver fibrosis., Methods: Fifteen clinically asymptomatic AATD patients (11 homozygous PiZZ, 4 heterozygous PiMZ) and 16 matched healthy volunteers were examined using MRE and ARFI quantification. Additionally, patients were examined with 2D-SWE., Results: A high correlation is evident for the shear wave speed (SWS) determined with different elastography methods in AATD patients: 2D-SWE/MRE, ARFI quantification/2D-SWE, and ARFI quantification/MRE (R = 0.8587, 0.7425, and 0.6914, respectively; P≤0.0089). Four AATD patients with pathologically increased SWS were consistently identified with all three methods-MRE, ARFI quantification, and 2D-SWE., Conclusion: The high correlation and consistent identification of patients with pathologically increased SWS using MRE, ARFI quantification, and 2D-SWE suggest that elastography has the potential to become a suitable imaging tool for the assessment of AATD-related liver fibrosis. These promising results provide motivation for further investigation of non-invasive assessment of AATD-related liver fibrosis using elastography.

The quantification of changes in geomechanical properties due to chemical reactions is of paramount importance for geological subsurface utilisation, since mineral dissolution generally reduces rock stiffness. In the present study, the effective elastic moduli of two digital rock samples, the Fontainebleau and Bentheim sandstones, are numerically determined based on micro-CT images. Reduction in rock stiffness due to the dissolution of 10% calcite cement by volume out of the pore network is quantified for three synthetic spatial calcite distributions (coating, partial filling and random) using representative sub-cubes derived from the digital rock samples. Due to the reduced calcite content, bulk and shear moduli decrease by 34% and 38% in maximum, respectively. Total porosity is clearly the dominant parameter, while spatial calcite distribution has a minor impact, except for a randomly chosen cement distribution within the pore network. Moreover, applying an initial stiffness reduced by 47% for the calcite cement results only in a slightly weaker mechanical behaviour. Using the quantitative approach introduced here substantially improves the accuracy of predictions in elastic rock properties compared to general analytical methods, and further enables quantification of uncertainties related to spatial variations in porosity and mineral distribution., Competing Interests: The authors declare no conflict of interest.

Psoriatic arthritis (PsA) is a chronic, seronegative spondyloarthropathy associated with psoriasis (PsO). Treatment options range from non-pharmacologic measures to NSAIDS, DMARDs, and biologics, depending on patient presentation. Secukinumab (Cosentyx©) is a new biologic treatment option that was approved for use in treating adult patients with PsA in October 2016. Our paper explores the clinical trial evidence available for secukinumab to examine its safety and efficacy as a therapeutic agent for the treatment of PsA. While indirect comparisons of indicate that secukinumab is as effective as other treatment options, further studies directly comparing available treatments will be necessary to establish its place in treatment guidelines. As these and other trials are conducted, the evidence produced will further elucidate the clinical potential of secukinumab as a treatment option for patients with rheumatologic disease.

Background: Little information exists on health of children with developmental disabilities (DDs) in the Canadian province of Manitoba., Method: The present authors linked 12 years of administrative data and compared health status, changes in health and access to health and social services between children with (n = 1877) and without (n = 5661) DDs living in the province, matched by age, sex and region of residence., Results: Children with DDs were significantly more likely than children in the matched comparison group to die before the age of 17 and have a history of respiratory illness, diabetes and injury-related hospitalizations. Children with DD also had significantly higher average number of ambulatory physician visits and higher rate of continuity of care., Conclusions: Children with DDs had poorer health status than the matched comparison group. The health disparities experienced by children with DDs persisted over time. Further population-based longitudinal research is needed in this area., (© 2016 John Wiley & Sons Ltd.)

The mechanisms underlying the effects of severe burn trauma are not well understood. We previously demonstrated the ability of nephrilin peptide (an iron-binding peptide believed to enter cells through iron-uptake pathways) to suppress aspects of the neuroinflammatory response in a rat scald model, as well as sepsis mortality in a mouse model. This study explores the effect of nephrilin on other clinically relevant outcomes in the rat scald model. In a rat scald model, animals were treated with nephrilin either in week 1 or week 2 post-burn. Measurements were made of serum glucose and creatinine as well as wound area by planimetry and body composition by DEXA. Given the potential role of iron, results were analyzed both for the entire cohort of animals and for the normoferremic (>100 ug/dL serum iron) subset of animals. Nephrilin improved body composition, wound healing, kidney function, and glycemic control. The first two effects were significant in normoferremic but not in hypoferremic animals suggesting an effect of iron status on burn injury outcomes. Nephrilin treatment modulates a number of relevant variables in the rat scald model.

Background: Perceived social exclusion (PSE) depends on individual access to resources (e.g. income and social networks) and recognition of a social status. Working provides individuals with both resources and a social status. This situation leaves the non-working population at a severe social disadvantage, which might partly be remedied by retirement., Objective: We expected to find differential effects on PSE when individuals retire. For individuals working until retirement the transition might be mostly associated with a loss of resources (leading to an increase in PSE) and for individuals not working before retirement the transition might be more strongly associated with an increase in social status (leading to a decrease in PSE)., Material and Methods: We used longitudinal data from the German Panel Study of Labor Market and Social Security (PASS) to estimate fixed effects panel regression models for 790 men and women experiencing the transition to retirement (4110 observations). Models were estimated separately for retired persons who worked or did not work prior to retirement., Results: At retirement those working prior to the transition reported lower levels of PSE than those not working. As expected retirement increased PSE for those previously working and for those not previously working retirement decreased PSE in the short term. Both effects remained stable after compensating for resource changes due to retirement., Conclusion: Retirement reduced the differences in PSE between previously working and non-working groups. For those previously working retirement seemed to depict a loss of social acceptance whereas for those previously not working retirement seemed to indicate a reduction of stigmatization. The previous effect of the labor market, however, continued to affect individuals in retirement for a long time.

Background: The integrated care system Gesundes Kinzigtal (ICSGK), one of the most comprehensive population-based ICS in Germany, started its work nearly 9 years ago. The ICSGK is pursuing the Triple Aim: improving the health of the population, improving the individual's experience of care, and at the same time reducing the per capita costs of care., Objectives: To evaluate the impact of the ICSGK on the Triple Aim., Materials and Methods: The ICSGK is being evaluated externally and internally via a mix of diverse quantitative and qualitative methods. This paper presents selected results for each Triple Aim dimension., Results and Conclusions: Regarding population health, most of the quality indicators examined by the external scientific evaluation show positive development. For example, the prevalence of patients with fractures among all insurants with osteoporosis is presented. In 2011, this prevalence was approximately 26 % in the "Kinzigtal" population (aged ≥ 20 years old) in comparison to 33 % in the control group. As far as patient experience is concerned, to the question "Would you recommend becoming a member of Gesundes Kinzigtal to your friends or relatives?" 92.1 % of those questioned answered "Yes, for sure" or "Yes, probably." Twenty-four percent of those questioned further stated that they would now live "more healthy" than before enrolment in the ICSGK. In the subgroup of questioned insurants who had objective agreements with their doctors 45.4 % answered in this way. On the subject of cost-effectiveness, for both participating socil health insurance schemes, cost savings relative to the costs normally expected for the ICSGK population concerned are observed every year. In the seventh intervention year (2012) the total is 4.56 million Euros for the AOK Baden-Württemberg (BW), which is a contribution margin of 146 Euros per insurant for the 31.156 insurants concerned (LKK BW = 322 Euros per insurant relative to cost savings). The results presented in this paper indicate positive effects in all three Triple Aim dimensions. Further longitudinal studies are recommended to validate those first results together with a detailed analysis to obtain in-depth insights into the specific influence of subcomponents of the total intervention.

Enterococcus faecalis has emerged as an important cause of life-threatening multidrug-resistant bacterial infections in the hospital setting. The pathogenesis of enterococcal infections has remained a relatively neglected field despite their obvious clinical relevance. The objective of this study was to characterize the interactions between mast cells (MCs), an innate immune cell population abundant in the intestinal lamina propria, and E. faecalis. This study was conducted with primary bone marrow-derived murine MCs. The results demonstrated that MCs exerted an antimicrobial effect against E. faecalis that was mediated both by degranulation, with the concomitant discharge of the antimicrobial effectors contained in the granules, and by the release of extracellular traps, in which E. faecalis was snared and killed. In particular, the cathelicidin LL-37 released by the MCs had potent antimicrobial effect against E. faecalis. We also investigated the specific receptors involved in the recognition of E. faecalis by MCs. We found that Toll-like receptors (TLRs) are critically involved in the MC recognition of E. faecalis, since MCs deficient in the expression of MyD88, an adaptor molecule required for signaling by most TLRs, were significantly impaired in their capacity to degranulate, to reduce E. faecalis growth as well as to release tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) after encountering this pathogen. Furthermore, TLR2 was identified as the most prominent TLR involved in the recognition of E. faecalis by MCs. The results of this study indicate that MCs may be important contributors to the host innate immune defenses against E. faecalis., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)