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Children with disabilities and rare or undiagnosed conditions and their families have faced numerous hardships of living during the COVID-19 pandemic. For those with undiagnosed conditions, the diagnostic odyssey can be long, expensive, and marked by uncertainty. We, therefore, sought to understand whether and how COVID-19 impacted the trajectory of children’s care. We conducted semi-structured qualitative interviews with 25 caregivers who, prior to the pandemic, were on a diagnostic odyssey for their children. Most caregivers did not report any interruptions to their child’s diagnostic odyssey. The greatest impact was access to therapy services, including the suspension or loss of their child’s in-person therapeutic care and difficulties with virtual therapies. This therapy gap caused caregivers to fear that their children were not making progress. Although much has been written about the challenges of diagnostic odysseys for children and their families, this study illustrates the importance of expanding the focus of these studies to include therapeutic odysseys. Because therapeutic odysseys continue regardless of whether diagnoses are made, future research should investigate how to support caregivers through children’s therapies within and outside of the COVID-19 context.

Purpose:Although stereotactic body radiotherapy (SBRT) is effective in early-stage non–small cell lung cancer (NSCLC), approximately 10%–15% of patients will fail regionally and 20%–25% distantly. We evaluate a novel circulating tumor cell (CTC) assay as a prognostic marker for increased risk of recurrence following SBRT.Experimental Design:Ninety-two subjects (median age, 71 years) with T1a (64%), T1b (23%), or T2a (13%) stage I NSCLC treated with SBRT were prospectively enrolled. CTCs were enumerated by utilizing a GFP-expressing adenoviral probe that detects elevated telomerase activity in cancer cells. Samples were obtained before, during, and serially up to 24 months after treatment. SBRT was delivered to a median dose of 50 Gy (range, 40–60 Gy), mostly commonly in four to five fractions (92%).Results:Thirty-eight of 92 subjects (41%) had a positive CTC test prior to SBRT. A cutoff of ≥5 CTCs/mL before treatment defined favorable (n = 78) and unfavorable (n = 14) prognostic groups. Increased risk of nodal (P = 0.04) and distant (P = 0.03) failure was observed in the unfavorable group. Within 3 months following SBRT, CTCs continued to be detected in 10 of 35 (29%) subjects. Persistent detection of CTCs was associated with increased risk of distant failure (P = 0.04) and trended toward increased regional (P = 0.08) and local failure (P = 0.16).Conclusions:Higher pretreatment CTCs and persistence of CTCs posttreatment is significantly associated with increased risk of recurrence outside the targeted treatment site. This suggests that CTC analysis may potentially identify patients at higher risk for regional or distant recurrences and who may benefit from either systemic therapy and/or timely locoregional salvage treatment.

Supplementary Tables and Figures

Supplementary Figure Legend from Effect of Ablation or Inhibition of Stromal Matrix Metalloproteinase-9 on Lung Metastasis in a Breast Cancer Model Is Dependent on Genetic Background

Matrix metalloproteinases (MMP) are a family of enzymes with a myriad of functions. Lately, we have come to realize that broad-spectrum inhibition of these enzymes, as was tried unsuccessfully in multiple phase III trials in cancer patients, is likely unwise given the protumorigenic and antitumorigenic functions of various family members. Here, we used the multistage mammary tumor model MMTV-PyVT to investigate roles for either MMP7 or MMP9 in tumor progression. We found no effect of genetic ablation of MMP7 or MMP9 on the multifocal tumors that developed in the mammary glands. Lack of MMP7 also had no effect on the development of lung metastases, suggesting that MMP7 is irrelevant in this model. In contrast, MMP9 deficiency was associated with an 80% decrease in lung tumor burden. The predominant cellular source of MMP9 was myeloid cells, with neutrophils being the largest contributor in tumor-bearing lungs. Experimental metastasis assays corroborated the role of host-derived MMP9 in lung metastasis and also facilitated determination of a time frame most relevant for the MMP9-mediated effect. The lung tumors from MMP9-deficient mice showed decreased angiogenesis. Surprisingly, the antimetastatic outcome of MMP9 ablation seemed to be dependent on strain. Only mice that had genetic background derived from C57BL/6 showed reduced metastasis, whereas mice fully of the FVB/N background showed no significant effect. These strain-specific responses were also observed in a study using a highly selective pharmacologic inhibitor of MMP9 and thus suggest that responses to MMP inhibition are controlled by genetic differences. [Cancer Res 2008;68(15):6251–9]

Supplementary Table 1 from Effect of Ablation or Inhibition of Stromal Matrix Metalloproteinase-9 on Lung Metastasis in a Breast Cancer Model Is Dependent on Genetic Background

Supplementary Figure 1 from Effect of Ablation or Inhibition of Stromal Matrix Metalloproteinase-9 on Lung Metastasis in a Breast Cancer Model Is Dependent on Genetic Background

The combustion, since the beginning of history of mankind, is the source of heat and work more used in an effective and reliable manner for energy conversion. The restrictions of the use of fossil fuels and growing concerns about the emission of pollutants in the atmosphere have generated a major breakthrough in researches in combustion processes improvement in recent decades. Pulsating Combustion has shown an interesting tool in the improvement of power generation, offering advantages over conventional combustion process due to a higher rate of mixing between the fuel and oxidant, increasing the turbulence in the region of flame, which generates a more efficient combustion and thus a reduction in the amount of fuel used. In this work will be presented the methodology of an experimental study of sizing an electrodynamic transducer for optimization of a baffle through the parameters suggested by ThilleSmal to reduce effectively the emissions of partial oxidation pollutant gases and particulates, increasing the convective heat transfer in the burner and lower capital investment for this process, when compared to the conventional ones. Therefore in the present work, the following steps were taken: a) the Thiele -Smal parameters for the electrodynamic transducer has been used; b) study of baffle assisted by analysis instruments and acoustic correction through RTA RTA technique (real time analyzer); c) use of pink signal generators and computational methods for simulation. After the steps previously presented, a scanning has been performed in the data in order to find the resonant frequency of the burner (natural frequency) which was used as a reference to tune the burner accordingly, the electrodynamic transducer and baffle. Through research has been observed that the electrodynamic transducer optimization for use in studies of pulsed flames favored the baffle design that got attuned to the natural frequency of the burner, providing greater efficiency of mixing fuel-oxygen in the air, increasing the heat exchange, that is the speed of heating has significantly increased by using a less cost implementation.

Resume Introduction Le stress est un facteur favorisant l’apparition et les exacerbations du psoriasis ainsi que l’intensite du prurit. Peu d’etudes ont ete realisees sur les effets du stress professionnel sur ces affections cutanees. Etudier l’association entre le stress professionnel et le niveau de prurit chez les patients atteints de psoriasis. Methode Il s’agit d’une etude prospective non-interventionnelle monocentrique. Les patients etaient des travailleurs atteints de psoriasis et etaient recrutes dans le service de dermatologie d’un centre hospitalier regional universitaire. Nous avons utilise le modele du desequilibre effort–recompense (effort–reward imbalance [ERI]) pour evaluer le stress professionnel et le questionnaire Itchy Quality of Life (ItchyQoL) pour le niveau de prurit des patients. Nous avons recueilli l’âge, le sexe, l’indice de masse corporelle, le traitement du psoriasis, la profession et le temps de travail hebdomadaire. L’association entre les scores ERI et ItchyQoL a ete etudiee a l’aide d’un modele logistique univarie. Resultats Trente patients ont ete inclus. La mediane du score ERI etait de 0,61. Six d’entre eux presentaient un desequilibre de la balance effort–recompense. La mediane du score ItchyQoL etait de 70. Nous n’avons retrouve aucune association significative entre le score ERI et le score ItchyQoL (p = 1). Discussion Il s’agit de la premiere etude sur les effets du stress professionnel issu du desequilibre effort–recompense sur le prurit. Cette etude preliminaire n’a pas permis de trouver une association significative entre le stress professionnel et le niveau de prurit chez des travailleurs atteints de psoriasis. Nous avons ete confrontes a des problemes pratiques de recrutement qui ont conduit a un effectif limite. Afin d’avoir une population plus importante et plus representative de la population generale atteinte de psoriasis, il faudrait mener une etude multicentrique en associant des dermatologues de ville et envisager d’autres options pour recruter davantage de patients.

To realize the promise of population genomic screening for rare medically actionable conditions, critical challenges in the return of normal/negative results must be understood and overcome. Our study objective was to assess the functioning of a new 13-item measure (CoG-NR) of understanding of and knowledge about normal/negative genomic screening results for three highly actionable conditions: Lynch Syndrome, Hereditary Breast and Ovarian Cancer, and Familial Hypercholesterolemia. Based on our prior research and expert review, we developed CoG-NR and tested how well it functioned using hypothetical scenarios in three Qualtrics surveys. We report on its psychometric properties and performance across the three different conditions. The measure performed similarly for the three conditions. Examinations of item difficulty, internal reliability, and differential item functioning indicate that the items perform well, with statistically significant positive correlations with genomic knowledge, health literacy, and objective numeracy. CoG-NR assesses understanding of normal/negative results for each of the conditions. The next step is to examine its performance among individuals who have actually undergone such tests, and subsequent use in clinical or research situations. The CoG-NR measure holds great promise as a tool to enhance benefits of population genomic screening by bringing to light the prevalence of incorrect interpretation of negative results.

Aim: Before population screening of ‘healthy’ individuals is widely adopted, it is important to consider the harms and benefits of receiving positive results and how harms and benefits may differ by age. Subjects & methods: Participants in a preventive genomic screening study were screened for 17 genes associated with 11 conditions. We interviewed 11 participants who received positive results. Results: Interviewees expressed little concern about their positive results in light of their older age, the risk condition for which they tested positive, or other pressing health concerns. Conclusion: Researchers and clinicians should recognize that returning positive results may not have the impact they presume given the diversity of the conditions screened and those who choose to undergo screening.

The Oak Ridge National Laboratory (ORNL) is the largest and most diverse energy, research, and development institution within the Department of Energy (DOE) system in the United States. As such, the site endures constant land development that creates rigorous growing conditions for urban vegetation. Natural resource managers at ORNL recognize that trees are an integral component of the landscape and are interested in characterizing the urban forest and their associated ecosystem services benefits. We evaluated the urban forest structure, quantified ecosystem services and benefits, and estimated economic value of resources using i-Tree Eco at ORNL. While this assessment captured over 1100 landscape trees, the ORNL Natural Resources Management for landscape vegetation can be expanded to include unmanaged landscapes, e.g. riparian areas, greenspace, and other vegetative attributes to increase ecosystem services benefits. Assigning a monetary value to urban forest benefits help to inform decisions about urban forest management, ideally on cost-benefit analysis.

The objective of this study was to investigate the association between dietary diversity, child growth and child developmental outcomes. This was a prospective cohort study. Developmental outcomes were assessed by communication, fine motor, gross motor, personal social, problem solving and combined developmental scores measured by the Extended Ages and Stages Questionnaire (EASQ) at a 6-month follow-up visit. Height and weight were measured at baseline and a 6-month follow-up. Baseline minimum dietary diversity (MDD) for children 6-23 months old was defined by consumption of five or more of the following food groups: (1) breast milk; (2) grains, roots and tubers; (3) legumes and nuts; (4) dairy products; (5) flesh foods; (6) eggs; (7) vitamin A-rich fruits and vegetables and (8) other fruits and vegetables. Participants were 117 children 6-23 months of age. Linear growth faltering was defined as a significant decline (p 0.05) in length-for-age Z-scores (LAZ) between baseline and follow-up. Regression models were performed. The study was conducted in rural eastern Democratic Republic of the Congo (DRC). MDD was positively associated with change in LAZ (coefficient: 0.87 [95% confidence interval [CI]: 0.33, 1.40]), and a reduced odds of stunting (LAZ -2) (odds ratio: 0.21 [95% CI: 0.07, 0.61]). MDD was also associated with a significantly higher combined EASQ-Z-scores (coefficient: 0.34 [95% CI: 0.003, 0.68], higher communication EASQ-Z-scores [0.50 {95% CI: 0.14, 0.85}], and higher personal social EASQ-Z-scores [0.46 {95% CI: 0.11, 0.82}]). This study provides further evidence demonstrating the need for interventions to improve dietary diversity among young children.

Cells of most bacterial species are around 2 µm in length, with some of the largest specimens reaching 750 µm. Using fluorescence, x-ray, and electron microscopy in conjunction with genome sequencing, we characterized Ca. Thiomargarita magnifica, a bacterium with an average cell length greater than 9,000 µm that is visible to the naked eye. We found that these cells grow orders of magnitude over theoretical limits for bacterial cell size through unique biology, display unprecedented polyploidy of more than half a million copies of a very large genome, and undergo a dimorphic life cycle with asymmetric segregation of chromosomes in daughter cells. These features, along with compartmentalization of genomic material and protein synthesis in membrane-bound organelles, indicate gain of complexity in the Thiomargarita lineage, and challenge traditional concepts of bacterial cells.One Sentence SummaryCa. T. magnifica are compartmentalized centimeter-long bacteria

Additional file 1. Additional materials.

Additional file 1. Interview guide for AT participants.

The advent of human gene editing has stimulated international interest in how best to govern this research. However, research on stakeholder views has neglected scientists themselves. We surveyed 212 scientists who use gene editing in their work. Questions captured views on oversight and use of somatic and germline human gene editing for treatment, prevention, and enhancement. More respondents were supportive of somatic than germline editing, and more supported gene editing for treatment compared to prevention. Few supported its use for enhancement. When presented with specific conditions, levels of support for somatic editing differed by type of condition. Almost all respondents said scientists and national government representatives should be involved in oversight, but only 28% said scientists are best positioned to oversee gene-editing research. These results can inform the development of sound approaches to research governance, demonstrating the importance of identifying specific gene-editing uses when considering oversight.

The SARS-CoV-2 pandemic generated the need to modify the current clinical educational model with the challenge of promoting safety and the continuity of clinical education through the use of virtual platforms. Since clinical training in hospital institutions cannot be substituted, a strategic training plan was developed to guarantee protection, safety, and academic continuity for students upon returning to clinical clerkships. The objective of this project was to develop and evaluate the impact of a massive hybrid training plan as an educative strategy to give the theoretical and practical knowledge required for the safe return of undergraduate students to their respective clinical activities in the context of this pandemic. An academic program was designed through a massive hybrid strategy to train 616 undergraduate students studying clinical cycles by presential, virtual, synchronous, and asynchronous activities. To know the program's impact, a study based on an initial evaluation and a final evaluation was carried out to evaluate the acquisition of the critical knowledge and skills of the program. A significant difference was found between the means of the initial and final evaluations (p

OBJECTIVE: In response to the COVID-19 pandemic, hospitals have developed visitor restriction policies in order to mitigate spread of infection. We reviewed hospital visitor restriction policies for consistency and to develop recommendations to highlight fair and transparent restrictions, exceptions, and appeals in policy development and implementation. DESIGN: Collection and analysis of public-facing visitor restriction policies during the first 3 months of the pandemic. SETTING: General acute care hospitals representing 23 states across all 4 major regions of the United States. PARTICIPANTS: A cohort of the 70 largest hospitals by total bed capacity. MEASUREMENTS: Characteristics of visitor restriction policies including general visitor restriction statement, changes/updates to policies over time, exceptions to policies, and restrictions specific to COVID-19-positive patients. RESULTS: Sixty-five of the 70 hospitals reviewed had public-facing visitor restriction policies. Forty-nine of these 65 policies had general "no-visitor" statements, whereas 16 allowed at least 1 visitor to accompany all patients. Sixty-three of 65 hospitals included exceptions to their visitor restriction policies. Setting-specific exceptions included pediatrics, obstetrics/gynecology, emergency department, behavioral health, inpatient rehabilitation, surgery, and outpatient clinics. Exceptions that applied across settings included patients at end of life and patients with disabilities. CONCLUSION: Visitor restriction policies varied significantly among hospitals in this review. These variances create challenges in that their fair application may be problematic and ethical issues related to allocation may arise. Five recommendations are offered for hospitals revising or creating such policies, including that offering transparent, accessible, public-facing policies can minimize ethical dilemmas. In addition, hospitals would benefit from communicating with each other in the development of visitor policies to ensure uniformity and support patients and family members as they navigate hospital visitation.

The population of older adults is increasing, indicating a need to examine factors that may prevent or mitigate age-related cognitive decline. The current study examined whether microstructural white matter characteristics mediated the relation between physical activity and executive function in older adults without any self-reported psychiatric and neurological disorders or cognitive impairment (N = 43, mean age = 73 y). Physical activity was measured by average intensity and number of steps via accelerometry. Diffusion tensor imaging was used to examine microstructural white matter characteristics, and neuropsychological testing was used to examine executive functioning. Parallel mediation models were analyzed using microstructural white matter regions of interest as mediators of the association between physical activity and executive function. Results indicated that average steps was significantly related to executive function (β = 0.0003, t = 2.829, P = .007), while moderate to vigorous physical activity was not (β = 0.0007, t = 1.772, P = .08). White matter metrics did not mediate any associations. This suggests that microstructural white matter characteristics alone may not be the mechanism by which physical activity impacts executive function in aging.

Additional file 1: Document with Figures S1 ��� S10.

This study evaluated the role of personality in predicting functional ability (FA) in older adults using self-report, collateral report, and performance-based measures of FA.Participants included older adults (N = 131) who completed a personality measure (NEO-FFI), a self-report of FA (OARS ADL), and participated in a performance-based assessment of FA (DAFS-R). In addition, each participant had a collateral complete a collateral report of FA (OARS ADL). Bivariate correlations were computed to assess how Five Factor Model traits were related to self-report, collateral, and performance-based measures of FA.These results suggest that personality traits can impact self-reported FA in older adults and underscore the importance of assessing FA in older adults using multiple methods, particularly performance-based measures.Clinicians should consider how personality may impact FA in older adults and multiple methods of FA performance should be examined to better tailor recommendations.

Understanding sex differences when assessing personality in older adults is important for researchers and clinicians. The current study utilized differential item functioning (DIF) to compare male and female older adults’ responses on the NEO-FFI to detect potential sources of measurement bias. Participants included 244 older adults (98 males, 146 females, mean age = 73). DIF by sex was determined using ordinal logistic regression and item response theory.Non-uniform DIF was present in item 31, and uniform DIF was present in item 26 in the Neuroticism scale. In the Extraversion scale, non-uniform DIF was present in items 32 and 37. In the Openness scale, non-uniform DIF was present in items 23 and 48; uniform DIF was present in items 53 and 58. Following Monte Carlo simulations to prevent overidentification, non-uniform DIF was present in item 31 in the Neuroticism scale and item 32 in the Extraversion scale. Results suggest that the NEO-FFI is a minimally biased measurement tool based on sex.

The hematological side effects associated with mycophenolic acid (MPA) are relatively common and have severe consequences. The majority of literature data have not shown clear consistency in the MPA exposure-neutropenia relationship. We hypothesized that (i) adult de novo kidney transplant recipients who develop neutropenia have relatively higher dose-normalized MPA exposure than patients without neutropenia, and (ii) the observed neutropenia may be explained by polymorphisms in metabolism and/or transporter genes responsible for MPA disposition. Adult kidney transplant recipients on steady-state tacrolimus and MPA, not receiving a corticosteroid, and with stable renal function were recruited for investigation at three periods post-transplant (1, 3, and 12 months; n = 21, 17, and 13, respectively). Clinical variables (age, weight, MPA daily dose, albumin, serum creatinine, absolute neutrophil count), tacrolimus and MPA concentrations (for exposure calculation), and genotypes (UGT2B7 G211T, UGT2B7 C802T, UGT1A9 T-275A, UGT1A9 T98C, MRP2 C-24T, MRP2 G1249A, OATP1B1 A388G, OATP1B1 C463A) were characterized. A significant inverse association between dose-normalized MPA exposure (a surrogate marker for apparent MPA clearance) and absolute neutrophil count in all three study periods (r2 ~ 0.3–0.7) was observed. No associations between characterized single nucleotide polymorphisms and MPA exposure or absolute neutrophil count were established. However, significant alterations in the minor allele frequencies of UGT2B7*2 C802T, UGT1A9 T275A, and MRP2 G1249A were evident. These findings support the clinical strategy for conducting MPA therapeutic drug monitoring in adult kidney transplant patients on steroid-free immunosuppressant therapy. The novel population genomic analysis data warrant further epidemiological investigations in a larger study sample.

This pilot study reports on a survey regarding recruitment, appointment, and training of members for health care ethics committees (HCECs).Past studies have examined HCECs, but have focused on the roles of the committees and the broad makeup of membership. Thus, our study fills an important knowledge gap in trends of membership recruitment and appointment processes employed by HCECs to comprise their membership.We posted our survey on several bioethics listservs between June and August 2015. Of the 103 respondents that started the survey, 59 were eligible for inclusion based on our criteria. We analyzed survey results descriptively and qualitatively.Overall we found no unifying standards of recruitment or appointment across the 59 respondents. Additionally, while responding committees varied in the professional backgrounds and attributes they valued in potential members, we found that most respondents valued traits of the applicants over specific knowledge or skills.This study provides a first look into how HCECs recruit members. Future research is needed to better understand the complexities of the issues discovered during this study, given that the HCEC members appointed are the individuals who fulfill committee obligations.

Background: Online study recruitment is increasingly popular, but we know little about the decision making that goes into joining studies in this manner. In GeneScreen, a genomic screening study that utilized online education and consent, we investigated participants' perceived ease when deciding to join and their understanding of key study features. Methods: Individuals were recruited via mailings that directed them to a website where they could learn more about GeneScreen, consent to participate, and complete a survey. Results: Participants found it easy to decide to join GeneScreen and had a good understanding of study features. Multiple regression analyses revealed that ease of deciding to join was related to confidence in one's genetic self-efficacy, limited concerns about genetic screening, trust in and lack of frustration using the website, and the ability to spend a limited time on the website. Understanding of study features was related to using the Internet more frequently and attaining more information about GeneScreen conditions. Conclusions: The ease of deciding to join a genomic screening study and comprehension of its key features should be treated as different phenomena in research and practice. There is a need for a more nuanced understanding of how individuals respond to web-based consent information.

Introduction Les lymphocytes T peripheral helper (Tph) constituent une sous-population decouverte recemment [1] , [2] , partageant avec les T follicular helper (Tfh) des fonctions d’aide a l’activation et a la maturation B, notamment via l’interleukine 21 (IL-21). Tph et Tfh expriment tous deux fortement PD-1 mais different par l’expression du recepteur de chimiokine CXCR5, ligand de CXCL13 permettant le homing au sein des structures lymphoides. L’objectif de ce travail etait d’analyser ces sous-populations lymphocytaires circulantes (Tph et Tfh) chez des patients atteints de polyarthrite rhumatoide (PR). Materiels et methodes Les patient inclus avaient une maladie active (DAS28 > 3,2), etaient naifs de biotherapie et debutaient un traitement par adalimumab. Les sous-populations lymphocytaires sanguines d’interet etaient identifiees par cytometrie de flux avant l’initiation de l’adalimumab (M0) et 3 mois apres (M3) en utilisant les marqueurs suivants : PD-1 + CXCR5-CD4+ pour les Tph, PD-1 + CXCR5 + CD4+ pour les Tfh. Leurs cytokines et chimiokines seriques associees (IL-21, CXCL13) etaient quantifiees par Luminex a M0 et M3. Les memes analyses etaient effectuees sur des temoins sains issus de dons de l’etablissement francais du sang. Les patients etaient suivis tous les 3 mois et la reponse clinique (DAS28 Resultats Trente et un patients ont ete inclus. Il s’agissait en majorite de femmes (20/31 ; 65 %), de 59 ans (28-77), dont la PR evoluait depuis 7 ans (0,75-43) et etait seropositive (Anti-CCP+ 27/31 ; 87 %). Dix-neuf temoins ont ete inclus, apparies en sexe, de 50 ans d’âge median (40-65). L’analyse des sous-populations lymphocytaires a M0 chez les PR comparee aux temoins a montre une surrepresentation des Tph, a la fois en nombre absolu et en pourcentage (p = 0,0325 ; p = 0,0002) ainsi que des Tfh (p = 0,0074 ; p = 0,0001). Les concentrations seriques d’IL-21 et de CXL13 etaient egalement significativement augmentees chez les patients comparativement aux temoins (p = 0,0024 et p = 0,0005). Parmi les patients, a M0, le nombre de Tph etait correle au titre d’anti-CCP (r = 0,47 ; p = 0,0125). Entre M0 et M3, seuls les Tfh ont significativement varie (diminution) sous adalimumab (p = 0,0022), independamment du statut repondeur ou non-repondeur. Aucune association n’a ete retrouvee entre la reponse clinique a M3, M6 ou M12 et le nombre ou le pourcentage des Tph et Tfh. Discussion Nous mettons en evidence une surrepresentation des Tph et Tfh circulantes dans la PR comparativement aux temoins, ainsi que de leurs cytokines et chimiokines associees et une correlation entre Tph et anti-CCP. Conclusion Ces donnees suggerent un potentiel role pathogene de ces cellules dans la PR, via l’activation lymphocytaire B et constituent d’interessantes futures cibles therapeutiques.

Today’s medical training environment exposes medical trainees to many aspects of what has been called “the hidden curriculum.” In this article, we examine the relationship between two aspects of the hidden curriculum, the performance of emotional labor and the characterization of patients and proxies as “bad,” by analyzing clinical ethics discussions with resident trainees at an academic medical center. We argue that clinicians’ characterization of certain patients and proxies as “bad,” when they are not, can take an unnecessary toll on trainees’ emotions. We conclude with a discussion of how training in ethics may help uncover and examine these aspects of the hidden curriculum.

Over the past decade, awareness emerged that existing frameworks for regulation and oversight of research with human participants fit poorly with contemporary research. Although substantial and diverse literature touches on this dissonance from a variety of perspectives, the problem is illustrated most clearly by the 2011 to 2017 process undertaken to “modernize” the Common Rule, the federal regulations for the protection of human research subjects. During this process, the Office for Human Research Protections (OHRP) sought public comment on a wide array of challenges they felt were not addressed adequately in existing regulations, and that they hoped to address in proposed revisions. The most widely debated proposal aimed to address a perception that a long-standing policy allowing the research use of nonidentified biospecimens without informed consent no longer made sense given the potential of genomic technologies to reidentify such samples.1 OHRP, recognizing concerns that existing regulations created undue burdens on very low-risk research, also proposed a plan to allow investigators to use a decision tool to determine whether a study would be “excluded” from IRB review. Proposals intended to address these and other concerns prompted critiques in the scholarly literature and in comments submitted to OHRP during the public comment period. Ultimately, the most controversial proposals, including requiring informed consent for nonidentified biospecimens research, were not part of the final rule published in January 2017 on the final day of the Obama administration. Two years after it was published, this final rule was implemented in January 2019. As leaders of a multi-disciplinary team working on the ethical and regulatory challenges raised by biorepository research in multi-site networks, we believe that both the controversy surrounding the OHRP proposals and the modest outcome of this six-year process are symptoms of a larger challenge. The regulatory revision process initiated by OHRP focused primarily on the transformation of biomedical science. Critically, however, it did not adequately consider the transformation that has occurred with regard to cultural perspectives on a range of critical issues relevant to the oversight of research with human subjects. These include, but are not limited to: changing perspectives on the right to privacy (and limits thereto), power imbalances between experts and lay people, trust in institutions, and individual ownership and control of data and biomaterials. OHRP, and the biomedical research community at large, have not resolved important questions about the oversight of human subjects research because we have not sufficiently accounted for the ways that society and societal norms have shifted since the Belmont Report was published 1979 and 45 CFR 46 Subpart A (what we now call the Common Rule) was adopted in 1981. It is time to undertake a different strategy for working toward the modernization of oversight and governance of research with humans. First, we need to revisit the principles articulated in the Belmont Report. If we aim to settle on an ethical framework that supports the development of policies, what ethical commitments and ideas must be included? Are additional ethical principles needed to ground this effort? Second, we need to conduct empirical research and public engagement activities to understand the views of diverse stakeholders on the ethical basis for policies on human subjects research. What implications do the Belmont principles hold for us today? Third, we need a process whereby this more contemporary interpretation of principles to guide human research ethics can be translated into policy and practice, with a focus that extends beyond the Common Rule to take a more comprehensive and global view of research oversight and governance. This work would recognize that changing societal contexts calls for changing approaches to process: a repeat of the original Belmont process would be an anachronism. While the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research successfully developed the original Belmont Report, it no longer makes sense for a small and distinguished group of scholars to gather at a conference center over a three-year period. Our proposal emphasizes a more transparent and inclusive – and thus more “modern” – process.

As large-scale biobanks are developed for translational genomic research and health care quality improvement, they are also becoming attractive as sites for public health interventions, such as population-based preventive sequencing for actionable variants. With the rapid advance of next-generation sequencing, the feasibility of such population health interventions is also increasing. The resulting confluence of public health norms, fiduciary clinical obligations, and ethical expectations for research creates a number of challenges. This chapter on public health genomics examines three examples of projects facing such challenges, in order to anticipate the ethical and policy issues that public health uses of research biobanks raise for those responsible for their design and governance. The chapter looks at issues of informed consent, return of results, and community engagement.

Introduction Les signes d’insuffisance cardiaque droite sont frequents dans l’evolution de la bronchopneumopathie chronique obstructive (BPCO) avec emphyseme sans que les mecanismes en cause soit clairement precises. Notre hypothese de travail est que l’emphyseme en majorant la pression intrathoracique provoque une dysfonction diastolique cardiaque droite a l’exercice en limitant l’expansion ventriculaire. Ainsi, une reduction d’emphyseme pourrait ameliorer la fonction diastolique ventriculaire droite. Methodes Lors du screening des patients BPCO avec emphyseme severe adresses pour une reduction endoscopique d’emphyseme, une evaluation hemodynamique invasive classique et avec un catheter a conductance permettant d’obtenir des boucles Pression/Volume au repos, a l’exercice et durant un test de lever de jambe, etait realise en cas de suspicion d’hypertension pulmonaire. Cette exploration etait repetee apres reduction d’emphyseme. La precharge, la fonction diastolique, la contractibilite, la fonction systolique, la postcharge et le couplage ventriculo-arteriel etaient ainsi enregistrees. Le critere de jugement principal est la compliance ventriculaire apres reduction d’emphyseme qui se traduit par une diminution de la pente relation pression volume telediastolique. Nous ne presentons ici que des donnees preliminaires. Resultats Nous avons pu obtenir la caracterisation hemodynamique de cinq patients dont trois ont eu une evaluation avant et apres reduction d’emphyseme. Concernant notre critere de jugement principal nos resultats preliminaires montrent une diminution de la pente relation pression volume telediastolique de respectivement 0,85 % et 0,95 % chez les deux patients ayant eu une reduction d’emphyseme versus une augmentation de 0,25 % chez le patient controle. Nos resultats secondaires montrent qu’apres reduction d’emphyseme on observe une augmentation de l’index cardiaque a l’effort rapporte a la valeur de repos (+ 55,4 % en post reduction versus + 3,4 % en pre reduction), du volume telediastolique (+ 28,5 % en post reduction versus − 2,3 % en pre reduction) tout en annulant l’augmentation de pression telediastolique a l’effort. Nous n’observons pas d’amelioration de la fonction systolique ni du couplage ventriculo-arteriel. Conclusion Ces premieres donnees permettent d’evaluer grâce a la technique de reference l’hemodynamique des patients BPCO avec emphyseme severe. Nos Resultats preliminaires vont dans le sens d’une amelioration de la fonction diastolique cardiaque droite par augmentation de compliance apres reduction d’emphyseme.

Mobility and cognitive impairments are common in persons with multiple sclerosis (MS), and are expected to worsen with increasing age. However, no studies, to date, in part due to limitations of conventional neuroimaging methods, have examined changes in brain activation patterns during active locomotion in older patients with MS. This study used functional Near Infrared Spectroscopy (fNIRS) to evaluate real-time neural activation differences in the pre-frontal cortex (PFC) between middle-aged to older adults with MS and healthy controls during single (Normal Walk; NW) and dual-task (Walking While Talking; WWT) locomotion tasks. Eight middle-aged to older adults with MS and eight healthy controls underwent fNIRS recording while performing the NW and WWT tasks with an fNIRS cap consisting of 16 optodes positioned over the forehead. The MS group had greater elevations in PFC oxygenation levels during WWT compared to NW than healthy controls. There was no walking performance difference between groups during locomotion. These findings suggest that middle-aged to older individuals with MS might be able to achieve similar levels of performance through the use of increased brain activation. This study is the first to investigate brain activation changes during the performance of simple and divided-attention locomotion tasks in MS using fNIRS.

Urban parks are important public resources for outdoor recreation in cities. While the previous studies have concluded that people in general value parks and trees, it is still unclear how public attitudes towards trees and tree-centered management of parks relate to their support for park management priorities, and whether such attitude vary among parks within a city. This study surveyed visitors’ opinion in three parks within the City of Oak Ridge, Tennessee and focused primarily on aspects of park trees to determine what visitors believed should be a future priority for park management. Exploratory factor analysis and multiple regression analysis were employed to data collected from 263 visitors intercepted on site (response rate of 78.5%). Results showed that visitors placed relatively higher preference on planting more trees, increasing species richness and density of trees, than on planting trees in straight rows or pruning or caring. Similarly, visitors placed comparatively higher preference on trees that are native, less hazardous, resistant to pests and diseases, have longer life span, provide shade, wildlife habitat, than those having ability to block out the view of city’s developed landscape. Results also showed that visitors’ personal preference of tree aspects and attitude towards trees significantly affected their support for future tree planting and tree care efforts in city parks. Findings will be useful to city planners, municipal foresters, and landscape designers in understanding public preference for trees and tree-oriented management, and incorporating such information in designing new parks, and enhancing amenity value of existing parks.

We are a multidisciplinary collaborative made up of bioethicists, social scientists, clinicians, and lawyers whose work focuses on the ethical challenges posed by a networked approach to bioreposit...

But Le savoir-faire technique en chirurgie robotique necessite de nouveaux modeles d’apprentissage. L’objectif de cette etude est d’evaluer l’apport du sujet anatomique re-perfuse et ventile par le systeme SimLife dans le cadre d’un masterclass de chirurgie robotique pediatrique. Materiel et methode Les corps donnes a la science sont draines de leur sang, remplace par un avatar visqueux au moyen de canules arterielles et veineuses, puis tracheotomises et ventiles. Douze chirurgiens experimentes venant de huit pays et six instructeurs ont evalue les six ateliers de chirurgie robotique a orientation thoracique, viscerale et urologique sur robots da Vinci (Xi, Si, X). Resultats (1) Tous les participants ont considere le masterclass tres utile (58 %) ou utile (42 %) pour leur activite professionnelle ; (2) modele facilitant l’apprentissage d’une procedure technique 73 % ; (3) realisme du modele 86 % ; (4) satisfaction generale du modele 80 %. Deux corps ont du etre remplaces apres la decouverte d’une fistule aorto-tracheo-oesophagienne et d’une volumineuse tumeur rectale meconnues, les causes de deces ne pouvant etre legalement divulguees. Un troisieme corps a ete remplace apres identification tardive d’une hemorragie arterielle, demontrant l’importance d’un solide briefing pre-chirurgie. Conclusion Le modele des cadavres re-perfuses et re-ventiles est une alternative pertinente pour l’apprentissage de la chirurgie robotique.

Background:Circulating anti-drug antibodies (ADAs) are detectable approximatively in 33% of adalimumab treated rheumatoid arthritis (RA) patients, often within the first 6 months of therapy1-2. Classically, circulating ADAs associate with their specific drugs to form immune complexes, increasing drug clearance, and by this mechanism reducing therapeutic effect3. B cell involvement leading to ADAs production is not yet well established.Objectives:To study early ADAs formation according to clinical response to an adalimumab therapy in RA patients and the relationship between ADAs and circulating B cell subsets.Methods:28 RA patients and 13 healthy controls were included. Patients all presented inadequately controlled RA under conventional treatment, were naive of biotherapies, and started an adalimumab treatment at baseline (M0). Responder status was determined according to the DAS28CRP score (3.2) at 3 (M3) and 6 months (M6). ADAs plasma concentration >10pg/mL at M3 defined the immunized patient group. Circulating B cell subsets were quantified by flow cytometry at M0 and M3.Results:11 (42.3%) patients were immunized at M3. Among them, 4 (36.4%) were responders at M6 and 7 (63.6%) were non-responders. Presence and concentration of ADAs at M3 was associated to non-responder status at M6 (p=0.043; p=0.042). Immunized patients had lower transitional B cells count at M0 compared to non-immunized patients (p=0.031).Conclusion:A high but classical proportion of RA patients developed ADAs after only 3 months of adalimumab treatment. This immunization was associated to non-responder status at M6 and to a low blood transitional B cells count at baseline. Our results suggest transitional B cells implication inRA activity and biotherapy resistance due to immunization. Low concentrations of transitional B cells could be an early biomarker of immunization process against adalimumab.References:[1]Bartelds GM et al. JAMA. 2011[2]Moots RJ et al. PLoS ONE. 2017[3]Van Schouwenburg PA et al. Ann Rheum Dis. 2013Table.Patients characteristics at baselineCharacteristicsAll RA patients (n=28)M6 responders(n=16)M6 non-responders(n=10)Age (years)60.5 [47-78]65.5 [47-76]54 [47-78]Sex ratio M/F (% of F)0.4 (71,4%)0.5 (68.8%)0.3 (80.0%)Disease duration, (years)5.6 [0.7-43.0]6.8 [1.0-43.0]2.9 [0.7-31.0]Oral steroid use, (%)18 (64,3%)9 (56.2%)8 (80.0%)Oral steroids, dose (mg/day)5.0 [2.0-15]5.0 [4.0-12.5]8.5 [2.5-15.0]Methotrexate use, (%)24 (50.9%)14 (87.5%)8 (80.0%)Methotrexate, dose (mg/week)20 [10-25]20 [10-25]15 [10-20]*Leflunomide use, (%)3 (10.7)1 (6.3%)2 (20.0%)Leflunomide, dose (mg/day)20 [20-20]20 [20-20]20 [20-20]CRP, (mg/dL)5.5 [1.0-57.0]6.6 [1.0-46.8]3.6 [1.0-57.0]DAS28CRP score4.3 [3.3-5.7]4.1 [3.3-5.2]4.5 [3.4-5.7]RF positive, (%)20 (71.4%)12 (75.0%)6 (60.0%)RF, (U/mL)116 [19-640]88 [21-640]181 [19-336]ACPA positive, (%)25 (89.3%)15 (93.8%)8 (80.0%)ACPA, (U/mL)340 [11-340]340 [14-340]340 [11-340]Values are medians with ranges and frequencies with percentages. *p=0.050.Figure 1.Graph 1Immunization against treatment at 3 months and clinical response at 6 months in RA patients (n=26). Presence of ADAs at 3 months is associated to non-responder status at 6 months. Fisher exact test. R, responders at 6 months; NR, non-responders at 6 months; ADA+, immunized patients at 3 months; ADA-, non-immunized patients at 3 months.Figure 2.Graph 2Absolute number of transitional B cells at baseline in RA patients (n=28) according to immunized status at 3 months. Immunized patients at 3 months had lower transitional B cells at baseline than non-immunized patients. ADA+, immunized patients at 3 months; ADA-, non-immunized patients at 3 months. Data represent the mean; *pDisclosure of Interests:None declared

Introduction The South East Asia Research Collaboration in HIV (SEARCH) RV411 clinical trial in Thailand was a systematic investigation of analytic treatment interruption (ATI) in individuals diagnosed and treated since Fiebig stage I acute HIV infection. Here, we explore decision‐making processes and perceptions of trial participation in a phase I trial that raised important ethical considerations, to identify potential areas of improvement in this relatively new field of HIV research. Similar considerations apply to other HIV phase I trials, especially those involving ATI, making this trial a model to identify challenges and opportunities in promoting informed choice. Methods Using longitudinal semi‐structured interviews and a validated questionnaire, we examined how decisions to join or decline the trial were made, whether there was evidence of decisional conflict, and reactions to the trial outcomes. We also explored contrasting views and experiences in this small trial cohort. We report analyses of data from these questionnaires and interviews, conducted from February through December of 2016 with the 14 SEARCH cohort participants who either joined (n = 8) or declined (n = 6) participation in RV411. Results The eight participants and six decliners had low overall decisional conflict, which remained low over time. Decision making was more difficult for decliners than participants, at least initially. While all interviewees described being satisfied with their decisions, our study identified important negative consequences for a few individuals, including seroconversion, negative experiences with optional procedures and disappointment due to rapid viral rebound. Conclusions Although our results reflect the experiences of a small group invited to join this trial, our overall finding of low decisional conflict even while some individuals reported negative experiences provides lessons for clinical trial investigators. We developed points‐to‐consider in helping participants make informed choices, to support participants during the trial and to support decliners in their decisions.

The hematological side effects associated with mycophenolic acid (MPA) are relatively common and have severe consequences. The majority of literature data have not shown clear consistency in the MPA exposure-neutropenia relationship. We hypothesized that (i) adult de novo kidney transplant recipients who develop neutropenia have relatively higher dose-normalized MPA exposure than patients without neutropenia, and (ii) the observed neutropenia may be explained by polymorphisms in metabolism and/or transporter genes responsible for MPA disposition.Adult kidney transplant recipients on steady-state tacrolimus and MPA, not receiving a corticosteroid, and with stable renal function were recruited for investigation at three periods post-transplant (1, 3, and 12 months; n = 21, 17, and 13, respectively). Clinical variables (age, weight, MPA daily dose, albumin, serum creatinine, absolute neutrophil count), tacrolimus and MPA concentrations (for exposure calculation), and genotypes (UGT2B7 G211T, UGT2B7 C802T, UGT1A9 T-275A, UGT1A9 T98C, MRP2 C-24T, MRP2 G1249A, OATP1B1 A388G, OATP1B1 C463A) were characterized.A significant inverse association between dose-normalized MPA exposure (a surrogate marker for apparent MPA clearance) and absolute neutrophil count in all three study periods (rThese findings support the clinical strategy for conducting MPA therapeutic drug monitoring in adult kidney transplant patients on steroid-free immunosuppressant therapy. The novel population genomic analysis data warrant further epidemiological investigations in a larger study sample.