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Abstract Despite the variety in sequencing platforms, mappers, and variant callers, no single pipeline is optimal across the entire human genome. Therefore, developers, clinicians, and researchers need to make tradeoffs when designing pipelines for their application. Currently, assessing such tradeoffs relies on intuition about how a certain pipeline will perform in a given genomic context. We present StratoMod, which addresses this problem using an interpretable machine-learning classifier to predict germline variant calling errors in a data-driven manner. We show StratoMod can precisely predict recall using Hifi or Illumina and leverage StratoMod’s interpretability to measure contributions from difficult-to-map and homopolymer regions for each respective outcome. Furthermore, we use Statomod to assess the effect of mismapping on predicted recall using linear vs. graph-based references, and identify the hard-to-map regions where graph-based methods excelled and by how much. For these we utilize our draft benchmark based on the Q100 HG002 assembly, which contains previously-inaccessible difficult regions. Furthermore, StratoMod presents a new method of predicting clinically relevant variants likely to be missed, which is an improvement over current pipelines which only filter variants likely to be false. We anticipate this being useful for performing precise risk-reward analyses when designing variant calling pipelines.

In 2010, under the guidance of the DGAI (German Society of Anaesthesiology and Intensive Care Medicine) and DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine), twelve German medical societies published the “Evidence- and Consensus-based Guidelines on the Management of Analgesia, Sedation and Delirium in Intensive Care”. Since then, several new studies and publications have considerably increased the body of evidence, including the new recommendations from the American College of Critical Care Medicine (ACCM) in conjunction with Society of Critical Care Medicine (SCCM) and American Society of Health-System Pharmacists (ASHP) from 2013. For this update, a major restructuring and extension of the guidelines were needed in order to cover new aspects of treatment, such as sleep and anxiety management. The literature was systematically searched and evaluated using the criteria of the Oxford Center of Evidence Based Medicine. The body of evidence used to formulate these recommendations was reviewed and approved by representatives of 17 national societies. Three grades of recommendation were used as follows: Grade “A” (strong recommendation), Grade “B” (recommendation) and Grade “0” (open recommendation). The result is a comprehensive, interdisciplinary, evidence and consensus-based set of level 3 guidelines. This publication was designed for all ICU professionals, and takes into account all critically ill patient populations. It represents a guide to symptom-oriented prevention, diagnosis, and treatment of delirium, anxiety, stress, and protocol-based analgesia, sedation, and sleep-management in intensive care medicine.

Targeted monitoring of analgesia, sedation and delirium, as well as their appropriate management in critically ill patients is a standard of care in intensive care medicine. With the undisputed advantages of goal-oriented therapy established, there was a need to develop our own guidelines on analgesia and sedation in intensive care in Germany and these were published as 2nd Generation Guidelines in 2005. Through the dissemination of these guidelines in 2006, use of monitoring was shown to have improved from 8 to 51% and the use of protocol-based approaches increased to 46% (from 21%).Between 2006–2009, the existing guidelines from the DGAI (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin) and DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin) were developed into 3rd Generation Guidelines for the securing and optimization of quality of analgesia, sedation and delirium management in the intensive care unit (ICU). In collaboration with another 10 professional societies, the literature has been reviewed using the criteria of the Oxford Center of Evidence Based Medicine. Using data from 671 reference works, text, diagrams and recommendations were drawn up. In the recommendations, Grade “A” (very strong recommendation), Grade “B” (strong recommendation) and Grade “0” (open recommendation) were agreed.As a result of this process we now have an interdisciplinary and consensus-based set of 3rd Generation Guidelines that take into account all critically illness patient populations.The use of protocols for analgesia, sedation and treatment of delirium are repeatedly demonstrated. These guidelines offer treatment recommendations for the ICU team. The implementation of scores and protocols into routine ICU practice is necessary for their success.

BackgroundWomen are more likely to present with genitourinary complaints immediately after exposure to interpersonal violence, but little is known about the long-term effects of violence on women's urologic health, including their susceptibility to bladder pain and infections.ObjectiveTo determine whether lifetime interpersonal violence exposure and current posttraumatic stress disorder (PTSD) symptoms are associated with the prevalence or severity of painful bladder symptoms and a greater lifetime history of antibiotic-treated urinary tract infections in community-dwelling midlife and older women.Study designWe examined the cross-sectional data from a multiethnic cohort of community-dwelling women aged 40 to 80 years enrolled in a northern California integrated healthcare system. Women completed structured self-report questionnaires about their past exposure to physical and verbal/emotional intimate partner violence and sexual assault. The symptoms of PTSD were assessed using the PTSD checklist for the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, Civilian version. Additional structured self-report measures assessed the current bladder pain, other lower urinary tract symptoms, and the history of antibiotic-treated urinary tract infections. Multivariable logistic regression models examined self-reported interpersonal violence exposure history and current PTSD symptoms in relation to current bladder pain and antibiotic-treated urinary tract infection history.ResultsAmong 1974 women (39% non-Latina White, 21% Black, 20% Latina, and 19% Asian), 22% reported lifetime interpersonal violence exposure, 22% reported bladder pain, and 60% reported a history of ever having an antibiotic-treated urinary tract infection. Lifetime experiences of sexual assault (odds ratio, 1.39; [95% confidence interval, 1.02-1.88]) and current PTSD symptoms (odds ratio, 1.96; [95% confidence interval, 1.45-2.65]) were associated with current bladder pain. A lifetime experience of physical intimate partner violence was associated with having a urinary tract infection at any time in life previously (odds ratio, 1.38; [95% confidence interval, 1.00-1.86]), as was emotional intimate partner violence (odds ratio, 1.88; [95% confidence interval, 1.43-2.48]), sexual assault (odds ratio, 1.44; [95% confidence interval, 1.09-1.91]), and current PTSD symptoms (odds ratio, 1.54; [95% confidence interval, 1.16-2.03]).ConclusionIn this ethnically diverse, community-based cohort, lifetime interpersonal violence exposures and current PTSD symptoms were independently associated with current bladder pain and the lifetime history of antibiotic-treated urinary tract infections in midlife to older women. The findings suggest that interpersonal violence and PTSD symptoms may be underrecognized markers of risk for urologic pain and infections in women, highlighting a need for trauma-informed care of these issues.

This paper, while not presenting a general discussion of authority in education, attempts to uncover some of the anomalies, paradoxes and tensions in the concept. It will argue for a revaluation of authority as an educational virtue, as a form of participatory guidance that is an aid to growth. The paper intends to help provoke continued debate over our perceived educational virtues and vices. I argue that virtuous authority is authority exercised from the point of view of a "larger experience and a wider horizon." If teachers' 'pedagogical imperative' is to bridge the gap between forms of knowledge and their pupils, then their practice will involve authority. I suggest here that such authority should be repositioned as participatory, immanent and democratic. As Dewey says, 'The need for authority is…constant…[I]t is the need for principles that are both stable enough and flexible enough to give direction to the processes of living in its vicissitudes and uncertainties.' In answer to this, I suggest that teachers practice their authority in order to create stable yet flexible, open and indeterminate, but not chaotic situations that combine with pupils' experiences in such a way as to enable educational growth. Authority practised as a form of participatory guidance, to pursue this Deweyan line of argument, can be 'an aid to freedom' and not freedom's enemy. This paper will argue that authority, so revalued, ought to be cultivated in our educational thought and practice. "Eds": This paper forms part of a Special Issue titled 'Beyond Virtue and Vice: Education for a Darker Age', in which the editors invited authors to engage in exercises of 'transvaluation'. Certain apparently settled educational concepts (from agency and fulfilment to alienation and ignorance) can be reinterpreted and transvaluated (in a Nietzschean vein) such that virtues become vices, and vices, virtues. The editors encouraged authors to employ polemics and some occasional exaggeration to reimagine educational values that are all too readily accepted within contemporary educational discourses.

Education is astonishingly simple. We have all been through it, whether as children or later in life--indeed, many of us are still going through it in some form or other; we all know what works; and we are all committed to realising its individual and social potential. Such a view of the matter might dispense with the need for philosophy of education altogether as the problems of education are seen as little more than puzzles to be solved. We know (or think that we know) what we want to achieve, the challenge is how to do so most efficiently. If only the virtues of education were that perspicuous, that simple. If only the vices were so easily identified and expunged. It turns out that education is astonishingly complex. The following chapters aspire to re-introduce a certain complexity that abstains from an all-too-easy understanding. They seek not to offer solutions, but complications, disruptions and dissensions. The authors assume positions against the usual associations and evaluations regarding certain words and phrases--a revaluation that turns the virtues to vices and the vices to virtues.

JET, the world’s largest operating tokamak with unique Be/W wall and tritium handling capability, completed a Deuterium-Tritium (D-T) campaign in 2021 (Maggi et al 29th Fusion Energy Conf. ) following a decade of preparatory experiments, dedicated enhancements, technical rehearsals and training (Horton et al 2016 Fusion Eng. Des. 109–111 925). Operation with tritium raises significant technical, safety and scientific challenges not encountered in standard protium or deuterium operation. This contribution describes the tritium operational requirements, pulses and technical preparations, new operating procedures, lessons learned and details on the achieved operational availability and performance. The preparation and execution of the recent JET tritium experiments benefitted from the previous experience in 1991 (Preliminary Tritium Experiment), 1997 (DTE1 campaign) and 2003 (Trace Tritium Campaigns) and consisted of the following five phases: technical rehearsals and scenario preparation, tritium commissioning, 100% tritium campaign, D-T campaign (DTE2), tritium clean-up. Following the clean-up JET resumed normal operation and is currently undertaking a further D-T campaign (DTE3).

ObjectivesTo describe the composition of the US provider workforce for adults with cancer older than 65 years and to determine whether there were differences in patients who received care from different providers (eg, nurse practitioners [NPs], physician assistants [PAs], and specialty physicians).DesignObservational, cross-sectional study.SettingAdults within the 2013 Surveillance, Epidemiology, and End Results cancer registries linked to the Medicare claims database.ParticipantsMedicare beneficiaries who received ambulatory care for any solid or hematologic malignancies.MeasurementsInternational Classification of Diseases, Ninth Revision (ICD-9), diagnosis codes were used to identify Medicare patient claims for malignancies in older adults. Providers for those ambulatory claims were identified using taxonomy codes associated with their National Provider Identifier number.ResultsA total of 2.5 million malignancy claims were identified for 201, 237 patients, with 15, 227 providers linked to claims. NPs comprised the largest group (31.5%; n = 4,806), followed by hematology/oncology physicians (27.7%; n = 4,222), PAs (24.7%; n = 3767), medical oncologists (10.9%; n = 661), gynecological oncologists (2.6%; n = 403), and hematologists (2.4%; n = 368). Rural cancer patients were more likely to receive care from NPs (odds ratio [OR] = 1.84; 95% confidence interval [CI] = 1.65-2.05) or PAs (OR = 1.57; 95% CI = 1.40-1.77) than from physicians. Patients in the South were more likely to receive care from NPs (OR = 1.36; 95% CI = 1.24-1.49).ConclusionsA large proportion of older adults with cancer receive care from NPs and PAs, particularly those who reside in rural settings and in the southern United States. Workforce strategies need to integrate these provider groups to effectively respond to the rising need for cancer care within the older adult population.

Background Influenza and influenza-like illness place significant burden on the NHS. Children with underlying health conditions are vulnerable to developing bacterial complications. Objective To strengthen the evidence base underlying antibiotic use in at-risk children with influenza-like illness. Design This programme comprised five separate work packages. Work package A investigated published and unpublished data from previously published literature and work package B explored attitudes of parents and general practitioners to influenza-like illness and antibiotics in at-risk children. This was followed by a clinical trial to assess the effectiveness of early co-amoxiclav (Augmentin®, GlaxoSmithKline UK) use at reducing reconsultation due to clinical deterioration (work package C), a nested sub-study to examine bacterial carriage indicators of antibiotic resistance (work package D) and a within-trial economic evaluation and clinical risk prediction analysis (work package E). Setting Interviews were conducted by telephone with general practitioners across the UK and parents/guardians in England (work package B). We conducted the clinical trial (work package C and nested work packages D and E) in general practices and ambulatory care services in England and Wales. Participants General practitioners and parents/guardians of at-risk children who previously had influenza-like illness participated in work package B. At-risk children with influenza-like illness aged 6 months to 12 years participated in work packages C and E and optionally in work package D. Interventions The intervention for the clinical trial was a 5-day course of co-amoxiclav 400/57 with dosing regimens based on British National Formulary guidance. Main outcome measures Hospital admission (work package A); findings from semi-structured interviews with patients and health-care professionals (work package B); proportion of patients who reconsulted owing to clinical deterioration (work package C); respiratory bacterial carriage and antibiotic resistance of potentially pathogenic respiratory tract bacteria at 3, 6, 9 and 12 months (work package D); and risk factors for reconsultation owing to clinical deterioration, quality of life (EuroQol-5 Dimensions, three-level youth version), symptoms (Canadian Acute Respiratory Infection and Flu Scale), health-care use and costs (work package E). Review methods For work package A, we searched the MEDLINE, MEDLINE In-Process, EMBASE, Science Citation Index and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases until 3 April 2013 with no language restrictions and requested unpublished data from authors of studies which had collected but not published relevant data. We included studies involving children up to 18 years of age with influenza or influenza-like illness from primary or ambulatory care settings. We used univariable meta-analysis methods to calculate odds ratios with 95% confidence intervals for individual risk factors. We reported our systematic review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 statement. Results Work package A analysed data from 28 articles reporting data from 27 studies. Neurological disorders, sickle cell disease, immunosuppression, diabetes and an age of

BackgroundResistance to antibiotics is rising and threatens future antibiotic effectiveness. 'Antibiotic targeting' ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence.AimTo undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs.MethodsA systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs.Trial registrationPROSPERO Registration number: CRD42023376769.

As synthetic biology expands and accelerates into real-world applications, methods for quantitatively and precisely engineering biological function become increasingly relevant. This is particularly true for applications that require programmed sensing to dynamically regulate gene expression in response to stimuli. However, few methods have been described that can engineer biological sensing with any level of quantitative precision. Here, we present two complementary methods for precision engineering of genetic sensors: in silico selection and machine-learning-enabled forward engineering. Both methods use a large-scale genotype-phenotype dataset to identify DNA sequences that encode sensors with quantitatively specified dose response. First, we show that in silico selection can be used to engineer sensors with a wide range of dose-response curves. To demonstrate in silico selection for precise, multi-objective engineering, we simultaneously tune a genetic sensor's sensitivity (EC50) and saturating output to meet quantitative specifications. In addition, we engineer sensors with inverted dose-response and specified EC50. Second, we demonstrate a machine-learning-enabled approach to predictively engineer genetic sensors with mutation combinations that are not present in the large-scale dataset. We show that the interpretable machine learning results can be combined with a biophysical model to engineer sensors with improved inverted dose-response curves.

Abstract Background The prehospital identification of stroke patients with large-vessel occlusion (LVO), that should be immediately transported to a thrombectomy capable centre is an unsolved problem. Our aim was to determine whether implementation of a state-wide standard operating procedure (SOP) using the Los Angeles Motor Scale (LAMS) is feasible and enables correct triage of stroke patients to hospitals offering (comprehensive stroke centres, CSCs) or not offering (primary stroke centres, PSCs) thrombectomy. Methods Prospective study involving all patients with suspected acute stroke treated in a 4-month period in a state-wide network of all stroke-treating hospitals (eight PSCs and two CSCs). Primary endpoint was accuracy of the triage SOP in correctly transferring patients to CSCs or PSCs. Additional endpoints included the number of secondary transfers, the accuracy of the LAMS for detection of LVO, apart from stroke management metrics. Results In 1123 patients, use of a triage SOP based on the LAMS allowed triage decisions according to LVO status with a sensitivity of 69.2% (95% confidence interval (95%-CI): 59.0–79.5%) and a specificity of 84.9% (95%-CI: 82.6–87.3%). This was more favourable than the conventional approach of transferring every patient to the nearest stroke-treating hospital, as determined by geocoding for each patient (sensitivity, 17.9% (95%-CI: 9.4–26.5%); specificity, 100% (95%-CI: 100–100%)). Secondary transfers were required for 14 of the 78 (17.9%) LVO patients. Regarding the score itself, LAMS detected LVO with a sensitivity of 67.5% (95%-CI: 57.1–78.0%) and a specificity of 83.5% (95%-CI: 81.0–86.0%). Conclusions State-wide implementation of a triage SOP requesting use of the LAMS tool is feasible and improves triage decision-making in acute stroke regarding the most appropriate target hospital.

ObjectiveIn 2013, the American College of Rheumatology published its Choosing Wisely list, which identified 2 radiographic procedures (peripheral joint magnetic resonance imaging [MRI] and dual x-ray absorptiometry [DXA] scans) that were at risk for overuse.MethodsWe performed a retrospective cross-sectional cohort study to measure the use of peripheral joint MRI, peripheral joint radiographs, and DXA scans in a national cohort of Medicare patients with rheumatoid arthritis (RA) during 2008-2009, before the start of the Choosing Wisely campaign. Diagnoses were identified via International Classification of Diseases, Ninth Revision, codes; utilization was calculated using Current Procedural Terminology codes. Utilization was analyzed at the individual level and at the regional level (by hospital referral region [HRR]).ResultsThere were 8,051 patients with RA who were included: 81% were women, and the mean age was 76 years. Over a 2-year period, the mean number of peripheral joint MRIs per beneficiary was 0.3 (median 0 [range 0-50]), peripheral joint radiographs per beneficiary was 2.6 (median 1 [range 0-33]), and DXA scans per beneficiary was 0.7 (median 0 [range 0-11]). Only 6.8% of patients received >1 peripheral joint MRI, and 6% of HRRs had a mean number of peripheral joint MRIs >1.ConclusionThere is variation in the use of peripheral joint MRI, peripheral joint radiographs, and DXA scans among Medicare patients with RA, although only a small number of HRRs have consistently high utilization. Although we cannot judge the appropriateness of each procedure, variation in use across regions signals the need for investigations to examine potential overutilization.

Purpose of reviewThis article reviews the evolution of quality measurement in rheumatology, highlighting new health-information technology infrastructure and standards that are enabling unprecedented innovation in this field.Recent findingsSpurred by landmark legislation that ties physician payment to value, the widespread use of electronic health records, and standards such as the Quality Data Model, quality measurement in rheumatology is rapidly evolving. Rather than relying on retrospective assessments of care gathered through administrative claims or manual chart abstraction, new electronic clinical quality measures (eCQMs) allow automated data capture from electronic health records. At the same time, qualified clinical data registries, like the American College of Rheumatology's Rheumatology Informatics System for Effectiveness registry, are enabling large-scale implementation of eCQMs across national electronic health record networks with real-time performance feedback to clinicians. Although successful examples of eCQM development and implementation in rheumatology and other fields exist, there also remain challenges, such as lack of health system data interoperability and problems with measure accuracy.SummaryQuality measurement and improvement is increasingly an essential component of rheumatology practice. Advances in health information technology are likely to continue to make implementation of eCQMs easier and measurement more clinically meaningful and accurate in coming years.

Hepatitis B virus (HBV) reactivation in the setting of rituximab use is a potentially fatal but preventable safety event. The rate of HBV screening and proportion of patients at risk who receive antiviral prophylaxis in patients initiating rituximab is unknown.We analyzed electronic health record (EHR) data from 2 health systems, a university center and a safety net health system, including diagnosis grouper codes, problem lists, medications, laboratory results, procedures codes, clinical encounter notes, and scanned documents. We identified all patients who received rituximab between 6/1/2012 and 1/1/2016. We calculated the proportion of rituximab users with inadequate screening for HBV according to the Centers for Disease Control guidelines for detecting latent HBV infection before their first rituximab infusion during the study period. We also assessed the proportion of patients with positive hepatitis B screening tests who were prescribed antiviral prophylaxis. Finally, we characterized safety failures and adverse events.We included 926 patients from the university and 132 patients from the safety net health system. Sixty-one percent of patients from the university had adequate screening for HBV compared with 90% from the safety net. Among patients at risk for reactivation based on results of HBV testing, 66% and 92% received antiviral prophylaxis at the university and safety net, respectively.We found wide variations in hepatitis B screening practices among patients receiving rituximab, resulting in unnecessary risks to patients. Interventions should be developed to improve patient safety procedures in this high-risk patient population.

Abstract Allostery is a fundamental biophysical mechanism that underlies cellular sensing, signaling, and metabolism. Yet a quantitative understanding of allosteric genotype‐phenotype relationships remains elusive. Here, we report the large‐scale measurement of the genotype‐phenotype landscape for an allosteric protein: the lac repressor from Escherichia coli, LacI. Using a method that combines long‐read and short‐read DNA sequencing, we quantitatively measure the dose‐response curves for nearly 105 variants of the LacI genetic sensor. The resulting data provide a quantitative map of the effect of amino acid substitutions on LacI allostery and reveal systematic sequence‐structure‐function relationships. We find that in many cases, allosteric phenotypes can be quantitatively predicted with additive or neural‐network models, but unpredictable changes also occur. For example, we were surprised to discover a new band‐stop phenotype that challenges conventional models of allostery and that emerges from combinations of nearly silent amino acid substitutions.

Objectives To characterise the quality of life, healthcare use and costs associated with early antibiotic treatment of influenza-like illness (ILI) in ‘at-risk’ children.Design Economic analysis of a two-arm double-blind parallel group pragmatic randomised controlled trial.Setting Children were recruited from community-based healthcare settings, including general practices, walk-in centres and hospital ambulatory care.Participants Children with risk factors for influenza-related complications, including respiratory, cardiac and neurological conditions, who presented within the first 5 days of an ILI.Interventions Co-amoxiclav 400/57 suspension or placebo.Outcome measures This economic analysis focused on quality of life measured by the EQ-5D-Y, symptoms assessed by the Canadian Acute Respiratory Infection and Flu Scale (CARIFS), healthcare use and costs including medication, hospital visits and admissions, general practitioner and nurse contacts. Outcomes were assessed for up to 28 days post randomisation.Results Information on resource use, EQ-5D-Y (day 28) and CARIFS (day 7) was available for 265 (98%), 72 (27%) and 123 (45%) out of 271 participants, respectively. Average costs in the co-amoxiclav group were £25 lower (95% CI −£113 to £65), but this difference was not statistically significant (p=0.566). The difference in EQ-5D-Y scores between groups was also not statistically significant (−0.014 (95% CI −0.124 to 0.096), p=0.798). However, day 7 CARIFS scores were 3.5 points lower in the co-amoxiclav arm (95% CI −6.9 to −0.1, p=0.044).Conclusions Our findings did not show evidence that early co-amoxiclav treatment improves quality of life or reduces healthcare use and costs in ‘at-risk’ children with ILI, but may reduce symptom severity though confirmation from further research would be important. Reliable data collection from children’s parents/carers was challenging, and resulted in high levels of missing data, which is common in pragmatic trials involving children with acute respiratory tract infections.Trial registration number ISRCTN70714783; EudraCT 2013-002822-21.

ObjectiveDespite looming rheumatologist shortages and a growing number of patients with arthritis and other rheumatic conditions, nationwide estimates of access to rheumatology care have never been reported. We aimed to measure travel times as a proxy to access to care and to determine the individual and area-level factors associated with long travel times to rheumatologists in the U.S.MethodsWe used Medicare Part B claims for the 2009 Medicare Chronic Condition Warehouse 5% rheumatoid arthritis/osteoarthritis cohort. Using Google Maps we estimated driving time from the center of a beneficiary's home ZIP code to the center of their rheumatologist's office ZIP code. We examined predictors of travel time ≥90 min in a series of generalized linear mixed models adjusting for rheumatologist supply, rurality, and individual patient characteristics including age, race, gender, and income.ResultsWe included 41,693 Medicare beneficiaries with 1 or more visits to a rheumatologist in 2009. The median estimated beneficiary travel time to a rheumatologist was 22 min [interquartile range (IQR): 12-40 min]. Overall, 7% of beneficiaries traveled 90 min or longer to visit a rheumatologist. Even after adjusting for covariates, independent predictors of long travel times included living in areas with no or low supply of rheumatologists and living in the Mountain region of the U.S.ConclusionsA small but significant proportion of patients in the U.S. traveled very long distances to visit a rheumatologist, and most of these individuals resided in areas with no or low supplies of rheumatologists. These data suggest that addressing shortages in rheumatology care for patients in low-supply areas is a key target for improving access to rheumatologists.

ObjectivePrior studies have established disparities by race/ethnicity and socioeconomic status (SES) in the kind, quantity, and technical quality of systemic lupus erythematosus (SLE) care and outcomes. In this study we evaluate whether disparities exist in assessments of interactions with health care providers and health plans and whether such interactions affect the technical quality of SLE care.MethodsData derive from the Lupus Outcomes Study (LOS). Principal data collection is an annual structured phone interview including items from the Consumer Assessment of Health Plans and Interpersonal Processes of Care Scale measuring dimensions of health care interactions. We use general estimating equations to assess whether disparities exist by race/ethnicity and SES in being in the lowest quartile of ratings of such interactions and whether ratings in the lowest quartile of interactions are associated with technical quality of care after adjustment for sociodemographic and disease characteristics.ResultsIn the 2012 LOS interview, there were 793 respondents, of whom 640 had ≥1 visit to their principal SLE provider. Nonwhite race/ethnicity and education were not associated with low ratings on any dimension of provider or system interaction; poverty was associated only with low ratings of health plan interactions. After adjustment for demographics, SLE status, and health care variables, ratings in the lowest quartile on all dimensions were associated with significantly lower technical quality of care.ConclusionRatings in the lowest quartile on all dimensions of interactions with providers and the health care system were associated with lower technical quality of care, potentially resulting in poorer SLE outcomes.

Slow and progressive loss of retinal ganglion cells (RGCs) is the main characteristic of glaucoma, the second leading cause of blindness worldwide. Previous studies have shown that impaired mitochondrial dynamics could facilitate retinal neurodegeneration. Mitochondrial dynamics are regulated directly (fission) or more indirectly (fusion) by dynamin-like protein 1 (DNML1). Therefore, DNM1L might be a promising target for an antibody-based approach to treat glaucoma. The consequences of targeting endogenous DNM1L by antibodies in a glaucoma animal model have not been investigated yet. Here, we show that the intravitreal application of an anti-DNM1L antibody showed protective effects regarding the survival of RGCs and their axons in the retinal nerve fiber layer (RNFL). Antibody treatment also improved retinal functionality, as observed by electroretinography (Ganzfeld ERG). Western blot analysis revealed altered DNM1L phosphorylation and altered expression of proteins related to apoptosis suggesting a decreased apoptosis rate. Mass spectrometry analysis revealed 28 up-regulated and 21 down-regulated proteins (p < 0.05) in both experimental groups. Protein pathway analysis showed that many proteins interacted directly with the target protein DNM1L and could be classified into three main protein clusters: Vesicle traffic-associated (NSF, SNCA, ARF1), mitochondrion-associated (HSP9A, SLC25A5/ANT2, GLUD1) and cytoskeleton-associated (MAP1A) signaling pathway. Our results demonstrate that DNM1L is a promising target for an antibody-based approach to glaucoma therapy.