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Objective: To develop, deploy, and evaluate a national, electronic health record (EHR)-based dashboard to support safe prescribing of biologic and targeted synthetic disease-modifying agents (b/tsDMARDs) in the United States Veterans Affairs Healthcare System (VA)., Data Sources and Study Setting: We extracted and displayed hepatitis B (HBV), hepatitis C (HCV), and tuberculosis (TB) screening data from the EHR for users of b/tsDMARDs using PowerBI (Microsoft) and deployed the dashboard to VA facilities across the United States in 2022; we observed facilities for 44 weeks post-deployment., Study Design: We examined the association between dashboard engagement by healthcare personnel and the percentage of patients with all screenings complete (HBV, HCV, and TB) at the facility level using an interrupted time series. Based on frequency of sessions, facilities were grouped into high- and low/none-engagement categories. We modeled changes in complete screening pre- and post-deployment of the dashboard., Data Collection Methods: All VA facilities were eligible for inclusion; excluded facilities participated in design of the dashboard or had <20 patients receiving b/tsDMARDs. Session counts from facility personnel were captured using PowerBI audit log data. Outcomes were assessed weekly based on EHR data extracted via the dashboard itself., Principal Findings: Totally 117 facilities (serving a total of 41,224 Veterans prescribed b/tsDMARDs) were included. Before dashboard deployment, across all facilities, 61.5% of patients had all screenings complete, which improved to 66.3% over the course of the study period. The largest improvement (15 percentage points, 60.3%-75.3%) occurred among facilities with high engagement (post-intervention difference in outcome between high and low/none-engagement groups was 0.17 percentage points (pp) per week, 95% confidence interval (0.04 pp, 0.30 pp); p = 0.01)., Conclusions: We observed significant improvements in screening for latent infections among facilities with high engagement with the dashboard, compared with those with fewer sessions., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Context.—: Serology plays a vital role in celiac disease (CD) diagnosis, and the latest European guidelines advocate for biopsy-free diagnoses in patients with ≥10× the upper limit of normal (ULN) of anti-tissue transglutaminase (tTG) immunoglobulin A (IgA) antibodies., Objective.—: To assess performance characteristics of a novel automated particle-based multianalyte technology (Aptiva) for anti-tTG and anti-deamidated gliadin peptide (DGP) antibody detection as compared to the traditional enzyme-linked immunosorbent assay (QUANTA Lite). Performance characteristics of the ≥10× ULN anti-tTG IgA criteria for serologic diagnosis of CD were also evaluated., Design.—: Sera samples from 703 patients were tested for anti-tTG IgA, anti-tTG immunoglobulin G (IgG), anti-DGP IgA, and anti-DGP IgG antibodies on both platforms. In total, 127 patients had medical information and were classified as CD-positive (n = 58) and CD-negative (n = 69) based on biopsy results. Clinical performance characteristics were evaluated., Results.—: Anti-tTG IgA detection showed equal clinical sensitivity and specificity of 91% sensitivity and 99% specificity on both platforms. Anti-tTG IgG resulted in moderate sensitivity of 69% and 72%, but high specificity of 100% and 94% on Aptiva and QUANTA Lite, respectively. Anti-DGP IgG displayed comparable sensitivity of 90% and 81%, and a specificity of 94% and 99%, on Aptiva and QUANTA Lite, respectively. Anti-DGP IgA demonstrated greater sensitivity on QUANTA Lite (83%) than Aptiva (69%) and similar specificities of 97% and 98% on QUANTA Lite and Aptiva, respectively. At ≥10× ULN levels for anti-tTG IgA, Aptiva displayed a sensitivity of 72% and a specificity of 100%, and QUANTA Lite showed a sensitivity of 69% and a specificity of 100%., Conclusions.—: Aptiva is a reliable method to measure CD biomarkers with reduced hands-on necessity and high-throughput capabilities. This study supports the use of a ≥10× ULN anti-tTG IgA biopsy-free approach for serologic diagnosis of CD., (© 2023 College of American Pathologists.)

Background: Hydroxychloroquine (HCQ) is commonly used for patients with autoimmune conditions. Long-term use of HCQ can cause retinal toxicity, but this risk can be reduced if high doses are avoided., Objective: We developed and piloted an electronic health record-based dashboard to improve the safe prescribing of HCQ within the Veterans Health Administration (VHA). We observed pilot facilities over a 1-year period to determine whether they were able to improve the proportion of patients receiving inappropriate doses of HCQ., Methods: Patients receiving HCQ were identified from the VHA corporate data warehouse. Using PowerBI (Microsoft Corp), we constructed a dashboard to display patient identifiers and the most recent HCQ dose and weight (flagged if ≥5.2 mg/kg/day). Six VHA pilot facilities were enlisted to test the dashboard and invited to participate in monthly webinars. We performed an interrupted time series analysis using synthetic controls to assess changes in the proportion of patients receiving HCQ ≥5.2 mg/kg/day between October 2020 and November 2021., Results: At the start of the study period, we identified 18,525 total users of HCQ nationwide at 128 facilities in the VHA, including 1365 patients at the 6 pilot facilities. Nationwide, at baseline, 19.8% (3671/18,525) of patients were receiving high doses of HCQ. We observed significant improvements in the proportion of HCQ prescribed at doses ≥5.2 mg/kg/day among pilot facilities after the dashboard was deployed (-0.06; 95% CI -0.08 to -0.04). The difference in the postintervention linear trend for pilot versus synthetic controls was also significant (-0.06; 95% CI -0.08 to -0.05)., Conclusions: The use of an electronic health record-based dashboard reduced the proportion of patients receiving higher than recommended doses of HCQ and significantly improved performance at 6 VHA facilities. National roll-out of the dashboard will enable further improvements in the safe prescribing of HCQ., (©Anna Montgomery, Gary Tarasovsky, Zara Izadi, Stephen Shiboski, Mary A Whooley, Jo Dana, Iziegbe Ehiorobo, Jennifer Barton, Lori Bennett, Lorinda Chung, Kimberly Reiter, Elizabeth Wahl, Meera Subash, Gabriela Schmajuk. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 12.05.2023.)

Ultrasound shear wave elastography (SWE) is an emerging modality for the estimation of stiffness, but it has not been studied in relation to common disorders with altered stiffness, such as bruxism, which affects almost one-third of adults. Because this condition could lead to an increased stiffness of masticatory muscles, we investigated SWE in bruxism according to a proof-of-principle and feasibility study with 10 patients with known bruxism and an age- and gender-matched control group. SWE of the left and right masseter muscles was estimated under three conditions: relaxed jaw, 50% of the subjective maximal bite force, and maximal jaw opening. Rejecting the null hypothesis, SWE was significantly increased during relaxed jaw (bruxism 1.92 m/s ± 0.44; controls 1.66 m/s ± 0.24), whereas for maximal mouth opening, the result was vice versa increased with 2.89 m/s ± 0.93 for bruxism patients compared with 3.53 m/s ± 0.95 in the healthy control, which could be due to limited jaw movement in chronic bruxism patients (bruxism 4.46 m/s ± 1.17; controls 5.23 m/s ± 0.43). We show that SWE in bruxism is feasible and could be of potential use for diagnostics and monitoring, though we also highlight important limitations and necessary methodological considerations for future studies.

Fully digital workflows gained acceptance in dental practice and thereby are of interest for undergraduate education. An exploratory clinical observation was designed to track the implementation of such a workflow with novice digital users in order to describe its feasibility, time investment, and pitfalls., Methods: Students were invited to provide feedback for their experiences with a training module that consisted of the following: intraoral scanning, computer-aided design (CAD), manual finishing, and insertion of a 3D-printed bite splint for the lower jaw., Results: A total of 82 fourth-year students participated in the module. The average time required to perform an intraoral scan was 17 m 5 s, and all students were able to design a splint with an average time of 2 h 38 m. Students who indicated prior experience with CAD seem to outperform inexperienced students in both CAD task completion and intraoral scanning. The initial fit was reported as clinically acceptable by 68.5% of the participants, while 79% rated the workflow as very good to satisfactory and indicated that the training was helpful for dental practice., Conclusions: The implementation of a digital workflow in undergraduate dental education is feasible and has acceptable clinical results. However, CAD is time-intensive, and the experience can be challenging.

Quality measures (QMs) are tools that help measure or quantify health care processes, outcomes, patient perceptions, and organizational structures and systems associated with the ability to provide high-quality health care. QMs are often developed from clinical practice guidelines (CPGs), as they summarize the best available evidence to create standards for optimizing patient care. The authors provide a framework for learners to understand the relevance, development, and testing of QMs in rheumatology, touching on their relationship to CPGs and appropriate use criteria. They describe measure implementation across different health care settings and reflect on challenges and opportunities associated with this process., Competing Interests: Disclosure Dr. Makris was a VA HSR&D Career Development Awardee at the Dallas VA (CDA 14-425). The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs., (Published by Elsevier Inc.)

Objective: Patient-reported outcomes (PROs) are an integral part of treat-to-target approaches in managing rheumatoid arthritis (RA). In clinical practice, however, routine collection, documentation, and discussion of PROs with patients are highly variable. The RISE LC (Rheumatology Informatics System for Effectiveness Learning Collaborative) was established to develop and share best practices in PRO collection and use across adult rheumatology practices in the United States METHODS: The goals of the RISE LC were developed through site surveys and in-person meetings. Participants completed a baseline survey on PRO collection and use in their practices. RISE LC learning sessions focused on improving communication around PROs with patients and enhancing shared decision-making in treatment plans. During the coronavirus disease 2019 (COVID-19) pandemic, the RISE LC pivoted to adapt PRO tools for telehealth., Results: At baseline, all responding sites (n = 15) had established workflows for collecting PROs. Most sites used paper forms alone. PRO documentation in electronic health records was variable, with only half of the sites using structured data fields. To standardize and improve the use of PROs, participants iteratively developed a Clinical Disease Activity Index-based RA Disease Activity Communication Tool to solicit treatment goals and improve shared decision-making across sites. The COVID-19 pandemic necessitated developing a tool to gauge PROs via telehealth., Conclusion: The RISE LC is a continuous, structured method for implementing strategies to improve PRO collection and use in rheumatological care, initially adapting from the Learning Collaborative model and extending to include features of a learning network. Future directions include measuring the impact of standardized PRO collection and discussion on shared decision-making and RA outcomes., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Direct silicone printing has been reported for the manufacture of interim facial prostheses. The recent advancements in printing hardware have allowed for multimaterial simultaneous silicone printing with 4 nozzles. With this technology, an auricular prosthesis was printed with various grades of Shore hardness. A few analog steps, including polishing, sealing, coloring, and relining, resulted in an individualized prosthesis with a thin frontal margin and smooth transition into the adjacent tissue. It was considered a definitive treatment option., (Copyright © 2020 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background: An identical homozygous missense variant in EIF3F, identified through a large-scale genome-wide sequencing approach, was reported as causative in nine individuals with a neurodevelopmental disorder, characterized by variable intellectual disability, epilepsy, behavioral problems and sensorineural hearing-loss. To refine the phenotypic and molecular spectrum of EIF3F-related neurodevelopmental disorder, we examined independent patients., Results: 21 patients were homozygous and one compound heterozygous for c.694T>G/p.(Phe232Val) in EIF3F. Haplotype analyses in 15 families suggested that c.694T>G/p.(Phe232Val) was a founder variant. All affected individuals had developmental delays including delayed speech development. About half of the affected individuals had behavioral problems, altered muscular tone, hearing loss, and short stature. Moreover, this study suggests that microcephaly, reduced sensitivity to pain, cleft lip/palate, gastrointestinal symptoms and ophthalmological symptoms are part of the phenotypic spectrum. Minor dysmorphic features were observed, although neither the individuals' facial nor general appearance were obviously distinctive. Symptoms in the compound heterozygous individual with an additional truncating variant were at the severe end of the spectrum in regard to motor milestones, speech delay, organic problems and pre- and postnatal growth of body and head, suggesting some genotype-phenotype correlation., Conclusions: Our study refines the phenotypic and expands the molecular spectrum of EIF3F-related syndromic neurodevelopmental disorder.

The plasma based synthesis of thin films is frequently used to deposit ultra-thin and pinhole-free films on a wide class of different substrates. However, the synthesis of thin films by means of low temperature plasmas is rather complex due to the great number of different species (neutrals, radicals, ions) that are potentially involved in the deposition process. This contribution deals with polymerization processes in a capacitively coupled discharge operated in a mixture of argon and aniline where the latter is a monomer, which is used for the production of plasma-polymerized polyaniline, a material belonging to the class of conductive polymers. This work will present a particular experimental approach that allows to (partially) distinguish the contribution of different species to the film growth and thus to control to a certain extent the properties of the resulting material. The control of the species flux emerging from the plasma and contributing to the film growth also sheds new light on the deposition process, in particular with respect to the role of the ion component. The analysis of the produced films has been performed by means of Fourier Transform Infrared spectroscopy (FTIR) and Near Edge X-ray Absorption Fine Structure spectroscopy (NEXAFS).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A comprehensive database of paleoclimate records is needed to place recent warming into the longer-term context of natural climate variability. We present a global compilation of quality-controlled, published, temperature-sensitive proxy records extending back 12,000 years through the Holocene. Data were compiled from 679 sites where time series cover at least 4000 years, are resolved at sub-millennial scale (median spacing of 400 years or finer) and have at least one age control point every 3000 years, with cut-off values slackened in data-sparse regions. The data derive from lake sediment (51%), marine sediment (31%), peat (11%), glacier ice (3%), and other natural archives. The database contains 1319 records, including 157 from the Southern Hemisphere. The multi-proxy database comprises paleotemperature time series based on ecological assemblages, as well as biophysical and geochemical indicators that reflect mean annual or seasonal temperatures, as encoded in the database. This database can be used to reconstruct the spatiotemporal evolution of Holocene temperature at global to regional scales, and is publicly available in Linked Paleo Data (LiPD) format.

Background: The utilization of intraoral scanning for manufacturing of complete dentures (CD) has been reported recently. However, functional border molding still cannot be supported digitally. A proof-of-concept trial shows two possible pathways to overcome this limitation by integrating a relining procedure into the digital workflow for CD manufacturing., Case Presentation: Intraoral scans and additional facial scans were performed with two various scanning systems for the rehabilitation of an edentulous male patient. The obtained raw data was aligned and used for the computer aided design (CAD) of the CD. The virtually constructed dentures were materialized in two various ways, considering rapid manufacturing and digital relining approaches in order to apply functionally molded borders., Conclusion: The use of intraoral edentulous jaws scans in combination with the digital relining procedure may allow for fabrication of CD with functional borders within a fully digital workflow.

In 1816, the coldest summer of the past two centuries was observed over northeastern North America and western Europe. This so-called Year Without a Summer (YWAS) has been widely attributed to the 1815 eruption of Indonesia's Mt. Tambora and was concurrent with agricultural failures and famines worldwide. To understand the potential impacts of a similar future eruption, a thorough physical understanding of the YWAS is crucial. Climate model simulations of both the 1815 Tambora eruption and a hypothetical analogous future eruption are examined, the latter occurring in 2085 assuming a business-as-usual climate scenario. Here, we show that the 1815 eruption drove strong responses in both the ocean and cryosphere that were fundamental to driving the YWAS. Through modulation of ocean stratification and near-surface winds, global warming contributes to an amplified surface climate response. Limitations in using major volcanic eruptions as a constraint on cloud feedbacks are also found.

Objective: We assessed implementation of the 10-item Patient-Reported Outcomes Measurement Information System (PROMIS) physical function form (PF-10a) in routine practice in a racially and ethnically diverse population with rheumatoid arthritis (RA). Objectives were to determine feasibility of implementing PF-10a in the electronic health record (EHR) and PF-10a validity and longitudinal responsiveness., Methods: Clinical and demographic data were abstracted from EHRs for all RA patients seen at a university-based rheumatology clinic between February 2013 and February 2015. We evaluated floor and ceiling (edge) effects and construct validity of PF-10a in a subgroup of patients with Health Assessment Questionnaire (HAQ) scores (n = 189). We used linear mixed-effects models to assess responsiveness of PF-10a to longitudinal changes in the Clinical Disease Activity Index (CDAI) for patients in the entire clinical cohort, with both scores recorded on at least 2 encounters (n = 326)., Results: Half of the patients were nonwhite, and 15% were non-English speakers. Over a 2-year period, PF10a was successfully implemented; 97% of patients and 89% of encounters had at least 1 measurement performed. PF-10a had fewer ceiling (defined as best) effects than the HAQ (8% versus 22%), and convergent validity was high (r = -0.85). PF-10a was sensitive to expected differences (older versus younger patients, more versus less active disease). Longitudinal changes in PF-10a were highly associated with changes in the CDAI score (P < 0.0001)., Conclusion: PF-10a was feasible to implement in a diverse RA population. It strongly correlates with the HAQ but has fewer ceiling effects and is responsive to changes in RA disease activity, suggesting its validity for use in routine clinical practice., (© 2016, American College of Rheumatology.)

Background: Treat-to-target is the recommended strategy for the management of rheumatoid arthritis (RA) and involves regular assessment of disease activity using validated measures and subsequent adjustment of medical therapy if patients are not in remission or low disease activity. Recommendations published in 2012 detailed the preferred disease activity measures but there have been few publications on implementation of disease activity measures in a real-world clinic setting., Methods: Plan-Do-Study-Act (PDSA) methodology was used over two cycles with a goal of increasing provider measurement of disease activity during all RA patient visits. In PDSA cycle 1, we implemented a paper-based form to help providers assess disease activity in RA patients. PDSA cycle 2 included the creation of separate patient and physician forms for collection of information, identification of patients prior to their clinic visit and incorporation of medical assistants into the workflow., Results: The first PDSA cycle improved the number of RA patients with documented disease activity measures from 24 % over a 4-week period, to an average of 44 % over an 8-week period. The second PDSA cycle showed a sustained and dramatic improvement, with 85 % of patients having a disease activity measure recorded over a 27-week period., Conclusions: Implementation of disease activity measurement in a typical academic rheumatology clinic can be achieved by standardizing workflow using a simple paper form.

Disruptions can prevent the classroom from being an effective learning environment. The Good Behavior Game (GBG) is a group contingency that has been proven to effectively prevent disruptions and increase engagement. However, the traditional methods of the GBG include teacher scanning for negative student behaviors, and may not align with Positive Behavioral Interventions and Supports (PBIS), which is becoming widely adopted in many schools. Extending the findings of Wright and McCurdy, the current study compared the effects of the GBG and a positive version of the GBG, called the Caught Being Good Game (CBGG), on student behavior, including engagement and off-task behaviors, as well as teachers' use of positive and negative statements. Results showed both the GBG and the CBGG improved student behavior, with data not clearly indicating one was superior. Neither intervention led to an increase in positive teacher statements. Implications for teachers and suggestions for further research are discussed., (© The Author(s) 2016.)

Objective: Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K)., Patients and Methods: A total of 1431 samples (SLE, n = 843; disease controls, n = 588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n = 566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off of > 4 was used to define active disease., Results: QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (p < 0.0001) in active SLE (SLEDAI-2K > 4; n = 232; median value 83.0 IU/mL) versus the inactive patients (n = 573; median value 22.3 IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearman's rho = 0.44, p < 0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity., Conclusions: The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity., (© The Author(s) 2016.)

Background: We describe the status of waterborne outbreaks notified in Norway and discuss this in the context of outbreaks recorded in previous years, to gain a better understanding of their development in Norway in recent years., Material and Method: We have collected information on all outbreaks notified to the Norwegian Institute of Public Health via the surveillance system for communicable diseases in the ten-year period from 2003-2012 for which drinking water was given as the suspected cause., Results: Altogether 28 waterborne outbreaks with a total of 8,060 persons reported as ill were notified in the period. The majority of outbreaks resulted in fewer than 100 cases of illness. There were two outbreaks with more than 1,000 cases of illness: an oubreak of campylobacteriosis in Røros and an oubreak of giardiasis in Bergen. In more than half of the outbreaks, water was supplied from public water distribution systems (16/28 outbreaks, 57%). In addition, a large proportion was linked to individual households with their own water supply (12/28 outbreaks, 43%)., Interpretation: Most of the outbreaks in the ten-year period were linked to public water distribution systems, while almost half were linked to non-disinfected water supplies to individual households. Although most of the outbreaks were small, two extensive outbreaks were also registered in the period, resulting in more than one thousand cases of illness. This underscores the need for good contingency planning and surveillance, so that suspicion of waterborne outbreaks is rapidly notified to the responsible authorities, and the importance of good protection of water sources, as well as proper maintenance of water treatment plants and distribution systems.

Rates of colon cancer are much higher in African Americans (65:100,000) than in rural South Africans (<5:100,000). The higher rates are associated with higher animal protein and fat, and lower fibre consumption, higher colonic secondary bile acids, lower colonic short-chain fatty acid quantities and higher mucosal proliferative biomarkers of cancer risk in otherwise healthy middle-aged volunteers. Here we investigate further the role of fat and fibre in this association. We performed 2-week food exchanges in subjects from the same populations, where African Americans were fed a high-fibre, low-fat African-style diet and rural Africans a high-fat, low-fibre western-style diet, under close supervision. In comparison with their usual diets, the food changes resulted in remarkable reciprocal changes in mucosal biomarkers of cancer risk and in aspects of the microbiota and metabolome known to affect cancer risk, best illustrated by increased saccharolytic fermentation and butyrogenesis, and suppressed secondary bile acid synthesis in the African Americans.

Background: Physicians frequently differ in their treatment recommendations. However, few studies have examined the reasons underlying these differences. The objective of this study was to examine whether physicians vary in the importance they attach to specific adverse events for two treatment options found in recent randomized controlled trials to have equivalent efficacy and overall toxicity., Methods: A Max-Diff survey was administered to physicians attending a national scientific conference to quantify the influence of 23 specific adverse events on decision making related to two treatment options for vasculitis. This approach was chosen because it results in greater item discrimination compared to rating scales. We used Hierarchical Bayes modeling to generate the relative importance score for each adverse event and examined the association between physicians' characteristics and the five most influential factors., Results: 118 physicians completed the survey. The mean age (SD) was 48 years (10); 68% were male and 81% reported spending the majority of time in clinical practice. There was significant variability in the ratings of the relative importance of all adverse events, except those that were mild and easily reversible. We found a positive correlation between increasing physician age with ratings of sepsis (r = 0.29, p = 0.002) and opportunistic infection (r = 0.23, p = 0.016), and an inverse association between age with progressive multifocal leukoencephalopathy (r = - 0.28, p = 0.003). Physician sex, work setting, location, and number of patients with vasculitis seen per year were not associated with the influence of specific adverse events on decision making., Conclusion: Our findings demonstrate that physicians differ substantially in how they perceive the importance of specific adverse events which may help explain observed unwarranted variability in physicians' recommendations in clinical practice. Further efforts are needed to ensure that the reasons underlying variability in physicians' recommendations are transparent.

Type 1 diabetes mellitus (T1D) is associated with decreased bone mineral density, a deficit in bone structure, and subsequently an increased risk of fragility fracture. These clinical observations, paralleled by animal models of T1D, suggest that the insulinopenia of T1D has a deleterious effect on bone. To further examine the action of insulin signaling on bone development, we generated mice with an osteoprogenitor-selective (osterix-Cre) ablation of the insulin receptor (IR), designated OIRKO. OIRKO mice exhibited an 80% decrease in IR in osteoblasts. Prenatal elimination of IR did not affect fetal survival or gross morphology. However, loss of IR in mouse osteoblasts resulted in a postnatal growth-constricted phenotype. By 10-12 weeks of age, femurs of OIRKO mice were more slender, with a thinner diaphyseal cortex and, consequently, a decrease in whole bone strength when subjected to bending. In male mice alone, decreased metaphyseal trabecular bone, with thinner and more rodlike trabeculae, was also observed. OIRKO mice did not, however, exhibit abnormal glucose tolerance. The skeletal phenotype of the OIRKO mouse appeared more severe than that of previously reported bone-specific IR knockdown models, and confirms that insulin receptor expression in osteoblasts is critically important for proper bone development and maintenance of structural integrity.

Objective: This study aimed to investigate changes in urodynamic findings and symptoms after detrusor injections of botulinum toxin A (BTX-A) in children with idiopathic detrusor overactivity (IDO) and urge incontinence., Material and Methods: Eight girls and five boys, aged 7-19 years, who had urge incontinence refractory to scheduled voiding and anticholinergics, were included this prospective study. Urodynamic studies showed postoperative IDO in 12 patients. A dose of 50-100 IU (1.3 -- 4.8 IU/kg) BTX-A was primarily administered at 15-20 detrusor sites. A control urodynamic study was performed within 3 months after the injections. Seven patients had a repeated procedure 16 (range 6-24) months on the average after the first one., Results: Eleven of the 13 patients had daily incontinence and two had incontinence a couple of times a week in association with urge symptoms. Postoperatively, no patient had urinary retention, but one girl had a urinary tract infection 4 months after the therapy. Five patients had a full response, seven partial responses and one no response 1-3 months after the first treatment. After 1 year, three of nine patients still have full response. Maximum cystometric capacity increased after the first treatment from a median of 227 ml to 379 ml (p = 0.005) and the number of patients with uninhibited detrusor contractions more than 30 cmH₂O during the filling phase decreased from eight to two out of 13 (p = 0.041)., Conclusions: Intradetrusor BTX-A injections effectively reduce day-time wetting, significantly increase bladder volume and decrease detrusor overactivity in children with urge incontinence refractory to scheduled voidings and anticholinergics.

Background: On October 29th 2009 the health authorities in the city of Trondheim, Norway were alerted about a case of Shiga toxin-positive E. coli (STEC) O145 in a child with bloody diarrhoea attending a day-care centre. Symptomatic children in this day-care centre were sampled, thereby identifying three more cases. This initiated an outbreak investigation., Methods: A case was defined as a child attending the day-care centre, in whom eae- and stx1- but not stx2-positive E. coli O145:H28 was diagnosed from a faecal sample, with multilocus variable number of tandem repeat analysis (MLVA) profile identical to the index isolate. All 61 children, a staff of 14 in the day-care centre, and 74 close contacts submitted faecal samples. Staff and parents were interviewed about cases' exposure to foods and animals. Faecal samples from 31 ewes from a sheep herd to which the children were exposed were analyzed for E. coli O145., Results: Sixteen cases were identified, from which nine presented diarrhoea but not haemolytic uremic syndrome (HUS). The attack rate was 0.26, and varied between age groups (0.13-0.40) and between the three day-care centre departments (0.20-0.50), and was significantly higher amongst the youngest children. Median duration of shedding was 20 days (0-71 days). Children were excluded from the day-care centre during shedding, requiring parents to take compassionate leave, estimated to be a minimum total of 406 days for all cases. Atypical enteropathogenic E. coli (aEPEC) were detected among 14 children other than cases. These isolates were genotypically different from the outbreak strain. Children in the day-care centre were exposed to faecal pollution from a sheep herd, but E. coli O145 was not detected in the sheep., Conclusions: We report an outbreak of stx1- and eae-positive STEC O145:H28 infection with mild symptoms among children in a day-care centre. Extensive sampling showed occurrence of the outbreak strain as well as other STEC and aEPEC strains in the outbreak population. MLVA-typing of the STEC-isolates strongly indicates a common source of infection. The study describes epidemiological aspects and socioeconomic consequences of a non-O157 STEC outbreak, which are less commonly reported than O157 outbreaks.

Background: Increasingly, women with a strong family history of breast cancer are seeking genetic testing as a starting point to making significant decisions regarding management of their cancer risks. Individuals who are found to be carriers of a BRCA1 or BRCA2 mutation have a substantially elevated risk for breast cancer and are frequently faced with the decision of whether to undergo risk-reducing mastectomy., Objective: In order to provide BRCA1/2 carriers with ongoing decision support for breast cancer risk management, a computer-based interactive decision aid was developed and tested against usual care in a randomized controlled trial., Design: . Following genetic counseling, 214 female (aged 21-75 years) BRCA1/2 mutation carriers were randomized to usual care (UC; n = 114) or usual care plus decision aid (DA; n = 100) arms. UC participants received no further intervention; DA participants were sent the CD-ROM-based decision aid to view at home., Main Outcome Measures: The authors measured general distress, cancer-specific distress, and genetic testing-specific distress at 1-, 6-, and 12-month follow-up time points postrandomization., Results: Longitudinal analyses revealed a significant longitudinal impact of the DA on cancer-specific distress (B = 5.67, z = 2.81, P = 0.005), which varied over time (DA group by time; B = -2.19, z = -2.47, P = 0.01), and on genetic testing-specific distress (B = 5.55, z = 2.46, P = 0.01), which also varied over time (DA group by time; B = -2.46, z = -2.51, P = 0.01). Individuals randomized to UC reported significantly decreased distress in the month following randomization, whereas individuals randomized to the DA maintained their postdisclosure distress over the short term. By 12 months, the overall decrease in distress between the 2 groups was similar., Conclusion: This report provides new insight into the long-term longitudinal effects of DAs.

Background: Systemic primary carnitine deficiency is an autosomal recessive disorder of the carnitine cycle caused by mutations in the SLC22A5 gene that encodes the carnitine transporter, organic cation transporter. Systemic primary carnitine deficiency typically presents in childhood with either metabolic decompensation or cardiomyopathy. We report five families in which low free carnitine levels in the infants' newborn screening have led to the diagnosis of maternal systemic primary carnitine deficiency., Methods: Blood samples from the infants and /or their family members were used to extract the DNA. The entire coding regions of the SLC22A5 gene were sequenced. The clinical data were obtained from the referring metabolic specialists., Result: Sequencing the SLC22A5 gene allowed molecular confirmation with identification of three novel mutations: c.1195C>T (p.R399W), c.1324&#95;1325GC>AT (p.A442I), and c.43G>T (p.G15W). All infants were asymptomatic at the time of diagnosis, and one was found to have systemic primary carnitine deficiency. Three mothers are asymptomatic, one had decreased stamina during pregnancy, and one has mild fatigability and developed preeclampsia., Discussion: These findings provide further evidence that systemic primary carnitine deficiency presents with a broad clinical spectrum from a metabolic decompensation in infancy to an asymptomatic adult. The maternal systemic primary carnitine deficiency was uncovered by the newborn screening results supporting the previous notion that newborn screening can identify some of the maternal inborn errors of metabolism. It also emphasizes the importance of maternal evaluation after identification of a low free carnitine level in the newborn screening.

Like humans, chimpanzees display robust and consistent hand preferences during the performance of certain tasks. Although correlations have been demonstrated between gross anatomic measures of primary motor cortex asymmetry and handedness in captive chimpanzees, the relationship between histological architecture and behavioral lateralization has not yet been investigated. Therefore, we examined interhemispheric asymmetry of several different microstructural characteristics of the primary motor cortex in the region of hand representation from 18 chimpanzees tested on a coordinated bimanual task before death. At the population level our data showed leftward bias for higher layer II/III neuron density. Of note, however, there was no population-level asymmetry in the areal fraction of Nissl-stained cell bodies, a finding that differs from previous studies of this cortical region in humans. Nonetheless, we found that asymmetry in the density of layer II/III parvalbumin-immunoreactive interneurons was the best predictor of individual hand preference. These results suggest that histological asymmetries are related to handedness in chimpanzees, while overall patterns of asymmetry at the population level might differ from humans., ((c) 2007 Wiley-Liss, Inc.)

Background: During maintenance work or breaks on the water distribution system, water pressure occasionally will be reduced. This may lead to intrusion of polluted water-either at the place of repair or through cracks or leaks elsewhere in the distribution system. The objective of this study was to assess whether breaks or maintenance work in the water distribution system with presumed loss of water pressure was associated with an increased risk of gastrointestinal illness among recipients., Methods: We conducted a cohort study among recipients of water from seven waterworks in Norway during 2003-04. One week after an episode of mains breaks or maintenance work on the water distribution system, the exposed and unexposed households were interviewed about gastrointestinal illness in the week following the episode., Results: During the 1-week period after the episode, 12.7% of the exposed households reported gastrointestinal illness in the household, compared with 8.0% in the unexposed households [risk ratio (RR) 1.58, 95% confidence interval (CI): 1.1, 2.3]. The risk was highest in households with higher average water consumption. The attributable fraction among the exposed households was 37% in the week following exposure., Conclusion: Our results show that breaks and maintenance work in the water distribution systems caused an increased risk of gastrointestinal illness among water recipients. Better data on the occurrence of low-pressure episodes and improved registration of mains breaks and maintenance work on the water distribution network are needed in order to assess the public health burden of contamination of drinking water within the distribution network.

Background: The prevalence of Giardia in Norway is considered to be low, but the infection is probably under-diagnosed. In other countries, child day-care centres have turned out to be major sites of Giardiasis contamination and outbreaks. We report the first giardiasis-outbreak registered in Norway., Materials and Methods: The outbreak occurred in a child day-care centre in Trondheim, Norway in 2004. Out of 12 microbiologically verified cases, 9 had clinical gastroenteritis. Stool samples were collected from all children and staff in the day-care centre, and from all household members of identified carriers. All carriers were treated with metronidazole and responded well to treatment. The environment of the child day-care centre was assessed, and all affected households were interviewed by telephone. Preventative measures were implemented., Results and Interpretation: The outbreak may have started in November 2003 and lasted until July 2004. It was limited to one of the day-care centre's five sections and 44% were infected. The source of infection was not identified, but there are several possibilities: staff who changed nappies and helped with going to the toilet also prepared and served food. Washbasin taps in kitchens and nappy-changing rooms were hand-operated. Cups used for drinking were exposed to potential contamination. These conditions are regarded as important routes for infections.

Given the pivotal role of nurses in providing and supervising patient care, it is essential that nursing professionals are engaged fully in making care safer. Nursing involvement was instrumental in the Michigan Health and Hospital Association Keystone ICU Project, which resulted in rapid reduction in catheter-related blood stream infection rates and ventilator-associated pneumonia rates. Nurses of every credential and every nursing position participated in this broad scale improvement effort. This article describes the MHA Keystone ICU Project, including challenges implicit in changing nursing practice and team behavior in the ICU. The improvement strategies implemented by Keystone ICU teams, and lessons learned by nurses engaged in the work, are likely to have application in other clinical settings.

We describe the application of cavity ring-down spectroscopy (CRDS) to the detection of trace levels of ethylene in ambient air in a cold storage room of a fruit packing facility over a several month period. We compare these results with those obtained using gas chromatography (GC), the current gold standard for trace ethylene measurements in post-harvest applications. The CRDS instrument provided real-time feedback to the facility, to optimize the types of fruit stored together, and the amount of room ventilation needed to maintain sub-10 ppb ethylene levels for kiwi fruit storage. Our CRDS instrument achieved a detection limit of two parts-per-billion volume (ppbv) in 4.4 minutes of measurement time.

Background: The number of individuals contemplating genetic testing is increasing, but the current materials and overall subject matter remain complex and not easily understood by many. The goal of this project was to evaluate efforts to revise and increase the readability of an existing information packet describing genetic risk for breast cancer., Methods: Evaluation was conducted in two stages through two related studies. In Study 1, a focus group of multiethnic breast cancer survivors was assembled to obtain feedback on images included in the revised breast cancer genetics information packet. In Study 2, African American adult students in a literacy program evaluated the revised images (based on the feedback of the focus group in Study 1) and text of the information packet and provided ratings on readability, format, and appearance., Results: Responses from Study 1 participants suggested that some of the images created for the packet needed to be clearer in the concepts they were intended to convey. In Study 2, ratings of adult learners suggested difficulty with word comprehension in spite of the inclusion of definitions and a glossary. The reading level achieved was markedly lower than the college reading level required by the original information packet and other patient-directed cancer genetics materials., Conclusions: Although efforts to clarify written materials in order to better serve patients with low literacy received generally favorable responses, continued efforts to create more user-friendly patient education materials are warranted.

In 1999-2000, a prospective case-control study of sporadic, domestically acquired campylobacteriosis was conducted in three counties in Norway to identify preventable risk factors and potentially protective factors. A total of 212 cases and 422 population controls matched by age, sex, and geographic area were enrolled. In conditional logistic regression analysis, the following factors were found to be independently associated with an increased risk of Campylobacter infection: drinking undisinfected water, eating at barbecues, eating poultry bought raw, having occupational exposure to animals, and eating undercooked pork. The following factors were independently related to a decreased risk: eating mutton, eating raw fruits or berries, and swimming. Results indicated that infection is more likely to occur as a result of cross-contamination from raw poultry products than because of poultry consumption per se. Drinking undisinfected water, reported by 53% of cases, was a leading risk factor in this study. Drinking water may constitute the common reservoir linking infection in humans and animals, including poultry and wild birds. Insight into the ecology of Campylobacter in freshwater ecosystems may be required to understand the epidemiology of campylobacteriosis. The possibility that certain foods confer protection against campylobacteriosis deserves exploration.

This study was designed to test the High Risk Model of Threat Perception in a family practice population. Predisposing, triggering, and buffering factors were assessed in 165 patients using psychological inventories. The relationship between these factors and self-reported symptoms, diagnosed chronic problems, and utilization was assessed. Negative affect and number and intensity of life events increased the risk for chronic illness and reported symptoms, while social support and approach style of coping decreased the apparent risk. The numbers of encounters and telephone calls to the office, obtained from the office database, were statistically correlated with negative affect and inversely with social support. The regression analysis predicted 27% of the variance in reported symptoms with negative affect, life events, and avoidance coping as significant predictors. Only 8% and 16% of the variance of telephone calls and office visits, respectively, could be predicted with a similar regression model. These results emphasize the importance of psychosocial factors in medical illness. Routine assessment of psychosocial risk factors in family practice patients is suggested.

Objective: To show that glomerular filtration rate (GFR) and bladder capacity (BC) develop isometrically, and to provide graphs for estimating GFR and BC for specific individuals of any age, sex, height and weight, for cystometric purposes., Materials and Methods: GFR and BC data were collected from published reports; graphs relating GFR and BC to age, sex, height and weight were obtained by using a computerized curve-fitting technique that minimizes the 1.1 power of the absolute error., Results: The plots show the GFR and BC for individuals of 10th, 50th and 90th percentile height and weight as a function of age and sex for different physiological conditions. GFR increases up to age 20 years and thereafter declines, whereas GFR per unit body surface area reaches a maximum at 3.25 years old and declines thereafter., Conclusions: The clinical management strategy to preserve or enhance renal function in paediatric and adult nephrological disease should incorporate the present data on development, growth, ageing and deterioration of function. These data should be used when interpreting cystometrograms and evaluating compliance. The graphs are useful for clinically estimating GFR and BC, especially when estimating infusion rate and BC for individual patients. BC and GFR develop isometrically with a proportionality constant of 4.56 min, except from birth to 1.5 years of age. Accordingly, individuals with healthy urinary systems, irrespective of age, sex and size, in the same physiological conditions have, on average, the same time to reach BC, ranging from 7 h at a normal 1% GFR to 41 min at the maximum diuresis of 10% GFR.

Context: Laboratory diagnosis of group A streptococcal pharyngitis in physician office and small-hospital laboratories., Objective: To characterize laboratory practices for the diagnosis of group A streptococcal pharyngitis and to identify opportunities for improvement., Design: Voluntary self-assessment questionnaire, used to assess the laboratory practices of 790 laboratories subscribing to the College of American Pathologists Excel Microbiology Proficiency Testing Program., Results: We observed discrepancies between self-reported and recommended specimen collection and laboratory testing practices for some laboratories. The most notable discrepancies were failing to provide a written specimen-collection procedure (17.8%), sampling the tongue and oral mucosa (2%), failing to always perform back-up cultures when rapid antigen test results were negative (57.5%), and finalizing culture reports within 24 hours or less (34.0%). Additionally, among those respondents who used the bacitracin disk, 57.9% (277 respondents) applied the disk directly onto a primary plate., Conclusions: Opportunities exist to improve testing practices for the diagnosis of group A streptococcal pharyngitis for some physician office and small-hospital laboratories.

Lysosomes are cell organelles in which macromolecules are recycled and that protect cells against toxins. In the present study, we apply histopathological and histochemical techniques in parallel with analytical chemistry of organochlorines and heavy metals in livers, with and without histopathological lesions, of the flatfish Plathichthys flesus (L.). The fish were caught along a pollution gradient on the German North Sea coast. We analyze critically whether changes in morphology and function of lysosomes, reflecting the onset and progression of toxipathic lesions in the liver of flounder, are appropriate for the rapid application in biological-effect monitoring programs such as BEEP (European Union Project in the 5th Framework Biological Effects of Environmental Pollutants in Marine Coastal Ecosystems). Livers collected from wild flounder were graded into four categories of lesions. Lysosomal stability was plotted against progressive lesions and contaminant levels in the same livers. Lysosomal membrane stability was already decreased at the onset of liver anomalies that are regarded as reversible. Reduced membrane stability also persisted in degenerative liver lesions and during carcinogenesis in liver parenchyma surrounding foci and tumors. Decreased lysosomal membrane stability coincided with increased size of lysosomes and increased lipid content during the progression toward degeneration. As predicted by the resistant-cell hypothesis, in proliferating cancer cells of adenomas and carcinomas, the highest values of membrane stability were detected. Concentrations of organochlorines such as hexachlorcyclohexane isomers, DDT metabolites, and polychlorinated biphenyls were correlated with reduced lysosomal membrane stability in noncancerous hepatocytes. On the basis of these findings, we recommend applying the lysosomal membrane stability test as an expertise-independent and rapid prognostic biomarker for toxically induced liver injury and carcinogenesis in monitoring programs.

Aims: To investigate whether a sheep flock was the original reservoir of a Shiga toxin-producing Escherichia coli (STEC) O103 strain causing a clinical human case and to compare the two diagnostic methods automated immunomagnetic separation (AIMS) and AIMS-ELISA., Methods and Results: AIMS detected Escherichia coli O103 in 36.5% of the samples and AIMS-ELISA detected E. coli O103 in 52.1% of the samples. Polymerase chain reaction detected stx1 and eae in three of 109 E. coli O103 isolates. Pulsed field gel electrophoresis showed that the sheep and human STEC O103 were characterized by distinctly different profiles., Conclusions: The sheep flock was shown to carry STEC O103, although an association between the sheep flock and the clinical human case could neither be proven nor eliminated. Substantial agreement was found between AIMS and AIMS-ELISA, but AIMS-ELISA was less time consuming and resulted in a higher recovery of E. coli O103., Significance and Impact of the Study: The study shows that sheep may be carriers of STEC that are associated with human disease and that the methods described can be used to increase the sensitivity of STEC detection.

Destruction of the urinary tract in children with elimination, storage, and holding dysfunction of the lower urinary and the distal GI tracts is caused primarily by high intravesical pressure. UTI accelerates this process. The LPP and the status of the urethral control mechanism and its relationship to the detrusor are the primary determinants of intravesical pressure. Intravesical pressures of more than 40 cm H2O are dangerous because they cause a pressure gradient that is transmitted proximally to the renal papillae, which results in the cessation of renal blood flow and a loss of renal function over time. Hydroureteronephrosis, VUR, UTI, urinary incontinence, and calculi formation also may occur. If these dangerously high intravesical pressures remain untreated, renal failure is likely to occur over time. These children then require dialysis or renal transplantation to survive, which is tragic and represents an enormous economic cost to society. Renal failure and upper urinary tract damage is nearly 100% preventable with early and appropriate evaluation and treatment. CIC is a crucial part of the management of these children and has been shown to be safe and effective, even in newborn boys. The use of the Credé maneuver (i.e., manual compression) to empty the bladder is obsolete and should be abandoned. The distal GI tract is inseparable from the lower urinary tract and must be treated simultaneously. Failure to treat the distal GI tract yields poor clinical results and much patient dissatisfaction and makes it difficult or impossible to treat the child's urinary tract problem successfully. Bowel-management programs must include daily high water and fiber intake, together with digital perianal stimulation or fecal extraction. Neuropathic bladder and bowel problems that are intractable to conservative medical and mechanical (i.e., CIC and digital perianal stimulation or fecal extraction, respectively) management almost always can be corrected surgically with high success rates in cooperative patients. Finally, neuropathic bladder and bowel problems can be extremely isolating and debilitating problems. Psychologic counseling and emotional support must be provided as needed. The care that these patients receive must be organized, comprehensive, and correlated with these patients' lifestyles. If these children are evaluated and treated early, they have the potential to live long, healthy, and productive lives.

Background and Purpose: A urodynamic test system of improved accuracy and reliability was developed and implemented for enhancing cystometry. This system integrates known medical information, including the specialized problems of pediatric urodynamics, with the cystometric and imaging data., Methods: After the requirements for the ideal cystometrogram test unit were established, a system was constructed, calibrated, and implemented in clinical practice. The patient's age, size, and sex are used to produce a patient-specific pressure-volume template for the cystometrogram test., Results: This template showed the minimal and normal bladder capacities and the physiologically safe, equivocal, and dangerous pressure fields coded with symbolic colors. Different time averages of the pressure data were used to show bladder factors such as compliance and instability. The templates with data were presented automatically (therefore objectively) without operator intervention on monitors during testing and as printed copies on completion., Conclusions: The presentation of data in an easily understood format facilitates effective communication between the urologist, referring physician, and patient. Some of the physiological and statistical problems in pediatric urodynamic testing are efficiently and accurately resolved by this system, resulting in better analysis and diagnostic capabilities.

Objective: To assess the status of office laboratory residency education and training in family practice, internal medicine, obstetrics and gynecology, and pediatric residency programs., Design: A single mailed survey to 1299 residency programs from December 1992 to February 1993., Participants: Primary care residency directors from 507 (39%) of 1299 programs., Interventions: A 27-item survey of residency-based office laboratory practices, education, training, and resources., Main Outcome Measures: Differences between specialties in provision and quantity of office laboratory education and training, presence of a residency-based office laboratory, laboratory classification under the Clinical Laboratory Improvement Amendments, and available laboratory tests., Results: Of those responding, office laboratories were present in 89% of family practice, 19% of internal medicine, 29% of obstetrics and gynecology, and 24% of pediatrics residency programs. Laboratory training was available at 60% of family practice, 16% of internal medicine, 15% of obstetrics and gynecology, and 30% of pediatrics programs. The median number of hours of formal skills training was 10 hours for family practice residency programs but less than 2 hours for the other specialties. Only 25% of the programs reported educational assistance from pathologists. Merely 4% of the programs had postassessment examinations and 2% awarded certificates of achievement. A majority of family practice programs performed waivered tests and physician-performed microscopy tests, but moderately complex tests were performed in less than 50% of family practice programs., Conclusions: Family practice residency programs provide more office laboratory training for residents than other specialties. There is a need for improved residency training in the basics of office laboratory practice.