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INTRODUCTION: Best practices for conducting advance care planning (ACP) among persons with cognitive impairment exist, but evidence‐based models are lacking for the primary care setting. METHODS: We tested a remote multicomponent ACP model (SHARE) versus minimally enhanced usual care in 273 person–family dyads from eight primary care practices. RESULTS: Mean patient age was 88.0 years, 85 (31.1%) were Black/Latino; 189 (69.2%) had moderate‐to‐severe cognitive impairment. Most (101/145; 69.6%) intervention dyads engaged in ACP. At follow‐up, no treatment effect was observed for care partner–reported quality of communication about end‐of‐life care at 6 or 12 months, but intervention patients reported better quality of communication about end‐of‐life care at 12 months. Intervention care partners and patients reported greater readiness to engage in ACP at 6 and 12 months, respectively, and increased completion of key aspects of ACP. DISCUSSION: SHARE supported key aspects of ACP processes and communication about end‐of‐life care. Highlights: Primary care–based models of ACP for persons with dementia are lacking.Involving persons with cognitive impairment in remote ACP is feasible with care partner involvement.Results indicate benefit for aspects of ACP processes and communication about end‐of‐life care. [ABSTRACT FROM AUTHOR]

Grape berry moths, particularly Lobesia botrana Denis & Schiffermüller (Lepidoptera: Tortricidae), and vinegar flies, such as Drosophila melanogaster Meigen and Drosophila suzukii Matsumura (Diptera: Drosophilidae), are important vineyard pests, causing severe quality loss of grapes. Several arthropod taxa may be involved in the natural control of these pests. However, the role of arthropod predators in the natural control of vineyard pests remains unclear. We investigated 32 vineyards in the Palatinate region, southwest Germany, under organic and conventional management, which in both cases received either full or reduced fungicide applications (2 × 2 design). Predation of L. botrana eggs and pupae and D. melanogaster pupae on sentinel cards exposed in the vineyards was observed with infrared cameras. In total, nine predator taxa could be identified. The most dominant predator was the European earwig, Forficula auricularia L. (Dermaptera: Forficulidae), with 90% of all predation events. We conclude that F. auricularia is likely a key predator of vineyard pests, and that special attention should be paid to maintain it at high population densities. [ABSTRACT FROM AUTHOR]

This paper aims to quantify the magnetospheric magnetic flux contents under moderate to intense space weather conditions using global simulations. This study is a companion to Akhavan‐Tafti, Atilaw, et al. (2023, https://doi.org/10.1029/2023JA031832) where magnetic flux evolution is presented for a catalog of storm events, using Heliophysics System Observatory (HSO) observations. For this study, we used the Space Weather Modeling Framework (SWMF) in Geospace configuration to study magnetic flux dynamics for a subset of their storm events (15 events). Simulations reliably resolve the storm‐time magnetic flux Bz and current density |J| asymmetries across the different storm phases. It is revealed that: relative to the quiet period, flux content is enhanced during the storm sudden commencement (SSC) phase in the dayside by ΔBz/Bz, quiet = +17%, and reduced in the nightside magnetosphere (r[RE] < −6 RE) by −15%. At the same time, the cross‐tail current is found to enhance (|J| = 2 nA/m2), which suggests the storm impact in the nightside magnetosphere is much earlier in the storm cycle than previously shown. Concurring with previous studies, a significant depletion of magnetic flux by up to −40%, with day‐night and dawn‐dusk asymmetries, can be seen during the main and recovery phases. This corresponds to the enhanced current density (|J| = 5–8 nA/m2) at ∼6 RE further confirming the role of ring current in driving magnetospheric dynamics during the main and recovery phases. This is in contrast with the SSC phase wherein the Chapman‐Ferraro and cross‐tail currents are the dominant current systems. Key Points: The nightside magnetospheric flux is impacted by the storm event earlier in the storm cycle than expected, (i.e., the SSC phase)Decrease in flux content of up to −40% within the inner magnetosphere for the main and recovery phases is associated with the enhanced ring currentStorm‐time asymmetries in magnetic flux and current density are well‐resolved throughout the storm phases [ABSTRACT FROM AUTHOR]

We analyze the local dynamics of magnetotail reconnection onset using Magnetospheric Multiscale (MMS) data. In conjunction with MMS, the macroscopic dynamics of this event were captured by a number of other ground and space‐based observatories, as is reported in a companion paper. We find that the local dynamics of the onset were characterized by the rapid thinning of the cross‐tail current sheet below the ion inertial scale, accompanied by the growth of flapping waves and the subsequent onset of electron tearing. Multiple kinetic‐scale magnetic islands were detected coincident with the growth of an initially sub‐Alfvénic, demagnetized tailward ion exhaust. The onset and rapid enhancement of parallel electron inflow at the exhaust boundary was a remote signature of the intensification of reconnection Earthward of the spacecraft. Two secondary reconnection sites are found embedded within the exhaust from a primary X‐line. The primary X‐line was designated as such on the basis that (a) while multiple jet reversals were observed in the current sheet, only one reversal of the electron inflow was observed at the high‐latitude exhaust boundary, (b) the reconnection electric field was roughly five times larger at the primary X‐line than the secondary X‐lines, and (c) energetic electron fluxes increased and transitioned from anti‐field‐aligned to isotropic during the primary X‐line crossing, indicating a change in magnetic topology. The results are consistent with the idea that a primary X‐line mediates the reconnection of lobe magnetic field lines and accelerates electrons more efficiently than its secondary X‐line counterparts. Key Points: Magnetotail reconnection onset was triggered by electron tearing during a solar wind pressure pulseOnset was characterized by the rapid collapse of the current sheet thickness and kinetic‐scale flux rope formationA primary X‐line was established within minutes of the onset [ABSTRACT FROM AUTHOR]

We analyze a magnetotail reconnection onset event on 3 July 2017 that was observed under otherwise quiescent magnetospheric conditions by a fortuitous conjunction of six space and ground‐based observatories. The study investigates the large‐scale coupling of the solar wind–magnetosphere system that precipitated the onset of the magnetotail reconnection, focusing on the processes that thinned and stretched the cross‐tail current layer in the absence of significant flux loading during a 2‐hr‐long preconditioning phase. It is demonstrated with data in the (a) upstream solar wind, (b) at the low‐latitude magnetopause, (c) in the high‐latitude polar cap, and (d) in the magnetotail that the typical picture of solar wind‐driven current sheet thinning via flux loading does not appear relevant for this particular event. We find that the current sheet thinning was, instead, initiated by a transient solar wind pressure pulse and that the current sheet thinning continued even as the magnetotail and solar wind pressures decreased. We suggest that field line curvature‐induced scattering (observed by magnetospheric multiscale) and precipitation (observed by Defense Meteorological Satellite Program) of high‐energy thermal protons may have evacuated plasma sheet thermal energy, which may require a thinning of the plasma sheet to preserve pressure equilibrium with the solar wind. Key Points: Magnetotail reconnection onset was observed during a fortuitous multiscale conjunction of the heliophysics observatoriesA transient solar wind pressure pulse triggered thinning and stretching of the cross‐tail current sheet without significant flux loadingA second solar wind pressure pulse caused the thinned current sheet to rapidly collapse and reconnect [ABSTRACT FROM AUTHOR]

BACKGROUND: Pesticides are considered main contributors to global arthropod declines and therefore may decrease the provision of ecosystem services such as natural pest control. Organic farming and cultivating pest‐ and disease‐resistant varieties can allow pesticide applications and their impacts on nontarget organisms and the environment to be reduced. We investigated the effects of organic versus conventional management and fungus‐resistant versus susceptible wine grape varieties on arthropod biodiversity and pest control of grape berry moths in 32 vineyards in the Palatinate region, Germany. Hazard quotients of applied pesticides were calculated for each vineyard. RESULTS: The cultivation of fungus‐resistant varieties led to significantly reduced hazard quotients and in turn enhanced abundances of natural enemies, particularly theridiid and philodromid spiders. Unexpectedly, organic management resulted in higher hazard quotients than conventional management and reduced numbers of natural enemies, particularly earwigs. Pest predation rates showed no significant differences between grape varieties or management types. CONCLUSION: Widespread benefits of organic management on arthropod biodiversity found in other crops were absent in our viticultural study region. This is likely due to the dominant role of fungal diseases in viticulture, which requires high numbers of fungicide treatments under both conventional and organic viticulture. Thus, fungicide reduction through the cultivation of fungus‐resistant grape varieties is one key element to fostering the abundance of arthropods in general and beneficial arthropods in particular. Beyond vineyards, this is potentially relevant in numerous other crop types. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Copyright of Nachrichten aus der Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An attraction of the profilometry‐based indentation plastometry (PIP) procedure is that, while it involves interrogation of volumes sufficiently large to ensure that bulk properties are obtained, it still allows stress–strain curves to be inferred for relatively small regions, such that local properties can be mapped where they are changing over short distances. It is employed here to obtain these characteristics as a function of depth in samples that have been case hardened by the diffusional penetration of carbon, to a depth of just over a mm. This has been done for a grade of steel that is commonly treated in this way. The thickness of the layer characterized by the PIP test is around 200 μm. In addition, curvature measurements on strip samples, after incremental removal of thin layers, have been used to evaluate the (compressive) residual stresses in near‐surface regions. These range up to around 200 MPa. Such stresses have only a small effect on the PIP measurements. The carburization raises the peak yield stress from the base level of around 1000 MPa to about 1400 MPa, followed by considerable work hardening. The reliability of these PIP‐derived stress–strain relationships has been confirmed by comparing experimental outcomes of Vickers hardness tests with FEM predictions based on their use. [ABSTRACT FROM AUTHOR]

Herein, it is concerned with the use of profilometry‐based indentation plastometry (PIP) to obtain mechanical property information for particulate metal matrix composites (MMCs). This type of test, together with conventional uniaxial testing, has been applied to four different MMCs (produced with various particulate contents and processing conditions). It is shown that reliable stress–strain curves can be obtained using PIP, although the possibility of premature (prenecking) fracture should be noted. Close attention is paid to scale effects. As a consequence of variations in local spatial distributions of particulate, the "representative volume" of these materials can be relatively large. This can lead to a certain amount of scatter in PIP profiles and it is advisable to carry out a number of repeat PIP tests in order to obtain macroscopic properties. Nevertheless, it is shown that PIP testing can reliably detect the relatively minor (macroscopic) anisotropy exhibited by forged materials of this type. [ABSTRACT FROM AUTHOR]

Managing eutrophied systems using only nutrient decreases to impose bottom–up control can be economically and ecologically challenging. Top–down controls through increased consumption have sometimes effectively controlled phytoplankton blooms. However, mechanistic insights, especially on possible trophic cascades, are less understood in brackish, species‐poor coastal waters, where large cladocera are absent. In this study, we set‐up large mesocosms for three consecutive years during the growing season. One set of mesocosms contained mesopredators (gobies and shrimps), whereas the other mesocosms had no such mesopredator present. The results were standardized to monitoring data from the ecosystem to track possible differences between treatments and the system. We found that mesopredator mesocosms showed lower turbidity, phytoplankton biomass and nutrients compared to no‐mesopredator mesocosms, and compared to the ecosystem. This decrease allowed macrophytes to colonize water depths only sparsely colonized in the ecosystem. Rotifer biomass increased in mesopredator mesocosms compared to the ecosystem and to the no‐mesopredator mesocosms. Likewise, copepod biomass that potentially grazes upon rotifers and other microzooplankton decreased in mesopredator mesocosms. No‐mesopredator mesocosms were colonized by an omnivorous mesograzer Gammarus tigrinus, potentially creating additional pressure on macrophytes and increasing grazing‐mediated nutrient release. Zooplankton was not able to control the non‐nutrient limited phytoplankton. We propose a new mechanism, where a higher mesopredator density will increase grazing on phytoplankton by promoting microzooplankton capable of grazing on picophytoplankton. This proposed mechanism would contrast with freshwater systems, where a decrease of zooplanktivorous fish would promote larger phytoplankton grazer like cladocera. Biomanipulation in such species‐poor eutrophic coastal waters may be more successful, due to less trophic pathways, that can cause complex top–down controls like in other systems. Stocking eutrophic coastal waters with gobies and shrimps may be an alternative biomanipulative approach rather than selectively removing large piscivorous or omnivorous fish from eutrophic coastal waters. [ABSTRACT FROM AUTHOR]

Copyright of Nachrichten aus der Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The quality of communication (QOC) questionnaire has been widely used to assess foundational aspects of patient‐clinician communication about end‐of‐life (EOL) care. However, this instrument has never before been fielded with primary care patients who have cognitive impairment and their caregivers, a population with unique communication needs. Design: We report on baseline data from a completed pilot study and ongoing efficacy trial of advance care planning involving dyads of primary care patients ages 80 and older with cognitive impairment and their family care partners. Two QOC subscales assessed ratings of general communication and EOL care communication from 0 ("worst") to 10 ("best"). Due to challenges piloting the EOL subscale, we integrated skip logic to improve cognitive accessibility and measurement precision. Participants were first asked whether EOL communication occurred (yes/no); those responding affirmatively were subsequently asked to rate communication. We report experiences with EOL subscale adaptations from our ongoing trial (NCT04593472). Results: Using the original instrument in our pilot (13 dyads), mean patient and family general communication ratings were similar (9.65 and 9.60, respectively), but EOL ratings diverged (4.23 and 5.88, respectively), and "Don't Know" comprised 5% of patient and 32% of family responses. Interviewers reported patient and family participants expressed confusion when asked to rate EOL communication behaviors that had not occurred. Using the adapted instrument in our efficacy trial (43 dyads), EOL communication behaviors were most often reported as not having occurred (76% of patient and 73% of family responses across all items). Mean patient and family EOL subscale ratings were similar (2.23 and 2.26) and responses of "Don't Know" were minimal (<1%). Conclusion: The original QOC EOL subscale involves rating conversations that rarely occur in primary care but are important for older adults with cognitive impairment. Subscale adaptations may reduce confusion and response uncertainty and improve measurement accuracy. [ABSTRACT FROM AUTHOR]

During a storm‐time interval around winter solstice, observations by the Magnetospheric Multi‐Scale (MMS) Mission show multiple distinct magnetopause boundary layers (BLs) in the vicinity of the southern cusp. The microphysics of the solar wind‐magnetosphere interaction during storm times are not well understood, because the observations are relatively lacking. This event enables the opportunity to probe the storm‐time magnetopause, and observations support that MMS was near a reconnection site equatorward of the southern cusp, suggesting active reconnection in close proximity to closed magnetic flux regions in the BL. The Grid Agnostic magnetohydrodynamics (MHD) for Extended Research Applications global MHD simulation shows evidence for transient secondary reconnection sites near the southern cusp, demonstrating mechanisms to form closed field line regions of the BL. Plain Language Summary: The physical processes by which the solar wind plasma penetrates Earth's magnetic shield are hotly debated. Furthermore, it is even less understood how the solar wind‐magnetosphere interaction plays out during geomagnetic storms, since observations are harder to obtain. Large geomagnetic storms sparked by strong solar activity occur only a few times yearly, and planning spacecraft observations during these times is extremely difficult. Fortunately, the Magnetospheric Multi‐Scale spacecraft constellation obtained storm‐time observations which provide the opportunity to reveal properties of the disturbed outer magnetosphere, in particular, at the interface of solar wind and geomagnetic fields. The event in this study shows magnetic reconnection occurring in an unusual location, which helps to understand the possible origin of the different observed boundary layers and how plasma is transported across them. Key Points: Around the minimum storm‐time SYM‐H, Magnetospheric Multi‐Scale encountered different magnetopause boundary layers (BLs) with multiple entries into the magnetosphereBz remains negative during one magnetopause crossing, indicating an encounter with the magnetosphere in the vicinity of the southern cuspObservations and global simulations support that secondary reconnection near the southern cusp produces closed BL magnetic flux [ABSTRACT FROM AUTHOR]

Herein, the effect of dispersed (relatively low levels of) porosity within a metal on its plastic deformation is examined. Stainless steel samples, made via additive manufacturing, are used in the work. It's found that porosity reduces stress levels during yielding and work hardening, approximately in proportion to the pore content. There is no significant difference between the strength of the effect during tension and compression, although porosity does reduce the tensile ductility. Finally, the profilometry‐based indentation plastometry (PIP) methodology (for obtaining stress–strain curves from indentation testing) are used. Porosity tends to bring the inferred yield stress down more strongly than during tensile testing and give higher initial rates of work hardening. This is associated with high local strains near the indenter causing closure of pores, so that volume is not conserved during the test. The resultant reduction in the pile‐up around the indent creates errors in the inferred stress–strain curve. [ABSTRACT FROM AUTHOR]

Fungicides make up the largest part of total pesticide use, with the dithiocarbamate mancozeb being widely applied as a nonsystemic contact pesticide to protect a wide range of field crops against fungal diseases. Although nematodes are key drivers of soil functioning, data on effects of fungicides, and especially mancozeb, on these nontarget organisms are scarce. Therefore, the effects of mancozeb on a soil nematode community from a natural grassland were assessed in small‐scale soil microcosms. Nematodes were exposed to mancozeb‐spiked soil in six nominal concentrations (7–133 mg/kg dry soil) and analyzed after 14, 56, and 84 days in terms of densities, genus composition, and functional traits. Because this fungicide is known to quickly degrade in soils (50% degradation time <1 day), mancozeb concentrations were analyzed for all sampling occasions. Chemical analysis revealed considerably lower measured concentrations compared with the aimed nominal soil concentrations at the beginning of the exposure (1–18 mg/kg dry soil), suggesting fast degradation during the spiking process. Nevertheless, the native nematode community responded sensitively to the fungicide mancozeb, revealing lower no‐observed‐effect concentration and 10% effect concentration (EC10) values than reported for other soil invertebrates such as springtails and earthworms. Using the EC10 for the most sensitive nematode community endpoint (percentage of predators and omnivores: 1.2 mg/kg dry soil), the risk assessment exhibited a toxicity exposure ratio of 0.66 and, thus, a high risk of mancozeb for soil nematodes. Keeping in mind their abundance and their central roles in soil food‐web functioning, the demonstrated sensitivity to a widely applied fungicide underscores the relevance of the inclusion of nematodes into routine risk‐assessment programs for pesticides. Environ Toxicol Chem 2022;41:2420–2430. © 2022 SETAC [ABSTRACT FROM AUTHOR]

Purpose: The primary endpoint results from the comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity (CARE‐ROP) core study identified ranibizumab as an effective treatment to control acute retinopathy of prematurity (ROP). This study reports the 1‐ and 2‐year follow‐up data focusing on long‐term functional outcomes and safety. Methods: The CARE‐ROP trial compared 0.12 mg versus 0.20 mg ranibizumab in 20 infants with ROP in a multicentric, prospective, randomized, double‐blind, controlled study design. Sixteen patients entered the follow‐up period. An ophthalmologic assessment at one year postbaseline was acquired from all 16 patients and a neurodevelopmental assessment at two years postbaseline was acquired from 15 patients. Results: Fifteen of 16 infants were able to fixate and follow moving objects at one year postbaseline treatment. One child progressed to stage 5 ROP bilaterally between the end of the core study and the 1‐year follow‐up (first seen at PMA 75 weeks). Mean spherical equivalents were −1.9 diopters (D) and −0.75 D in the 0.12 mg and the 0.20 mg treatment arms. Strabismus was present in seven and nystagmus in five out of 16 infants. Mental development scores were within normal limits in six out of ten patients with available data. No statistically significant difference was observed between the two treatment arms. Conclusion: Neurodevelopmental and functional ocular outcomes 1 and 2 years after treatment with ranibizumab are reassuring regarding long‐term safety. Late reactivation of ROP, however, represents a challenge during the follow‐up phase and it is of utmost importance that regular follow‐ups are maintained. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate invasive hemodynamics in assessing MC therapy success as well as evaluate its effectiveness as a predictor of functional outcomes. Background: Mitral regurgitation grade is a poor predictor of functional outcomes after a MitraClip. There is a paucity of data on invasive hemodynamics as a predictor of outcomes. Methods: Sixty‐nine patients underwent MC between 2015 and 2018 at the University of Minnesota Medical Center and were retrospectively analyzed. Invasive hemodynamics were performed before and after device deployment with transesophageal echocardiographic guidance. Statistical analysis was performed using STATA version 16. Student's t test was used for continuous variables and Pearson's chi‐squared test for categorical variables. Mann‐Whitney test was performed for continuous variables where data were not normally distributed. Logistic and linear regression were used to investigate relationships between variables and outcomes. Results: A total of 69 patients were included in the study. The mean age was 83 (75‐87) years and 38 (55%) were male. Eighty‐one percentage had >/= NYHA III symptoms. Eighty‐seven percentage had severe MR. Pulmonary capillary wedge pressure was 20 (15‐24). Overall, there was significant improvement in left atrial pressure including mean left atrial pressure index, MR, and NYHA class after MC (<.001). There was no significant association between invasive hemodynamics (including left atrial mean pressure index or its reduction rate) and functional outcomes (p = NS). MR grade was also not predictive of functional outcomes. Conclusion: Left atrial pressure may not be a significant predictor of functional outcomes, and, in isolation, may not be an improvement over MR grade. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to evaluate pediatric patients using existing macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH) scoring systems to determine how these systems identify patients with cytokine storm syndrome (CSS) in the setting of a multisystem inflammatory syndrome in children (MIS‐C) and active coronavirus disease 2019 (COVID‐19) infection. Methods: Hospitalized pediatric patients with MIS‐C and active COVID‐19 infection at a single institution were identified. Infectious data, clinical findings, and laboratory values were collected, and patients were stratified by disease severity. Eight historically used scoring systems for MAS, HLH, and CSS were examined in the cohort of patients with MIS‐C and pediatric COVID‐19. Results: The HLH‐2004 criteria and HScore did not identify any patients as having CSS on admission, with only one patient with COVID‐19 meeting criteria at peak disease severity. The 2016 systemic juvenile idiopathic arthritis (sJIA)/MAS criteria, ferritin/erythrocyte sedimentation rate (ESR) ratio, and COVID‐19 CSS Quick Score most frequently identified CSS in this population and distinguished between COVID‐19 and MIS‐C hyperinflammation. The 2019 MAS/sJIA (MS) score and the COVID‐19–associated hyperinflammatory syndrome (cHIS) criteria were less likely to identify CSS, as the MS score overestimated CSS and the cHIS resulted in similar scores regardless of severity or disease type. The Caricchio COVID‐Cytokine Storm (COVID‐CS) criteria identified patients with COVID‐19 frequently but was less useful in MIS‐C because of its COVID‐19‐specific criteria. Conclusion: MIS‐C and pediatric COVID‐19 result in relatively unique CSSs and patterns of inflammation. Existing scoring systems for CSSs likely do not capture the full breadth of this disease process in MIS‐C and pediatric COVID‐19. [ABSTRACT FROM AUTHOR]

The impact of COVID‐19 varies markedly, not only between individual patients but also between different populations. We hypothesised that differences in human leukocyte antigen (HLA) genes might influence this variation. Using next generation sequencing, we analysed the class I and class II classical HLA genes of 147 individuals of European descent experiencing variable clinical outcomes following COVID‐19 infection. Forty‐nine of these patients were admitted to hospital with severe respiratory disease. They had no significant pre‐existing comorbidities. We compared the results to those obtained from a group of 69 asymptomatic hospital workers who evidence of COVID exposure based on blood antibody testing. Allele frequencies in both the severe and asymptomatic groups were compared to local and national healthy controls with adjustments made for age and sex. With the inclusion of hospital staff who had reported localised symptoms only (limited to loss of smell/taste, n = 13) or systemic symptoms not requiring hospital treatment (n = 16), we carried out ordinal logistic regression modelling to determine the relative influence of age, BMI, sex and the presence of specific HLA genes on symptomatology. We found a significant difference in the allele frequency of HLA‐DRB1*04:01 in the severe patient compared to the asymptomatic staff group (5.1% vs. 16.7%, P =.003 after adjustment for age and sex). There was a significantly lower frequency of the haplotype DQA1*01:01‐DQB1*05:01‐DRB1*01:01 in the asymptomatic group compared to the background population (P =.007). Ordinal logistic regression modelling confirmed the significant influence of DRB1*04:01 on the clinical severity of COVID‐19 observed in the cohorts. These alleles are found in greater frequencies in the North Western European population. This regional study provides evidence that HLA genotype influences clinical outcome in COVID‐19 infection. Validation studies must take account of the complex genetic architecture of the immune system across different geographies and ethnicities. [ABSTRACT FROM AUTHOR]

This paper concerns, the effect of (unknown) residual stresses in the near‐surface region of a sample on outcomes of an indentation plastometry technique for obtaining stress–strain relationships, using relatively large spherical indenters. The technique is based on the iterative finite element method (FEM) simulation of indentation, so as to infer the true stress–strain curve of the material (with the target outcome being the profile of the residual indent). It is expected that residual stress levels (if significant compared with the yield stress) are likely to influence the outcome, and indeed this forms the basis of many attempts to measure residual stresses in this way (using a known stress–strain curve). However, there are important issues of sensitivity here, which affect the reliability of such procedures and are also relevant to the accuracy of stress–strain curves inferred from measurements made on samples containing unknown levels of residual stress. Herein, both experimental work on samples with (equal‐biaxial) residual stresses created by the application of external loads and extensive FEM modeling to explore various scenarios are covered. The main conclusion is that the sensitivities involved are in general very low, particularly with relatively deep indentation. Inferred stress–strain curves are thus likely to be quite accurate, even in the presence of relatively high levels of residual stress. Conversely, the measurement of residual stress levels via this procedure is likely to be rather inaccurate, although the reliability is improved using shallow penetration (low ratio of depth‐to‐indenter radius). It is also noted that tensile residual stresses tend to influence outcomes more strongly than compressive ones. [ABSTRACT FROM AUTHOR]

We analyze data returned by the Magnetospheric Multiscale mission (MMS) constellation during a rapid (∼1.5 s) traversal of a flapping and reconnecting current sheet (CS) in the near-Earth magnetotail (X ∼−20 RE). The CS was highly tilted, with its normal pointing strongly duskward. Its extreme thinness was confirmed by a curvature analysis of the magnetic field lines. The event was associated with a guide field of 8% of the reconnecting components. From the pitch angle distributions of low-energy electrons we infer a crossing earthward of the X-line. Traveling practically normal to the CS, MMS encountered an ion diffusion region (IDR) in which was embedded an electron diffusion region (EDR). IDR signatures included breaking of the ion frozen-in condition in the presence of Hall B and E fields. EDR signatures included a strong out-of-plane current associated with a superAlfvénic electron jet, positive energy transfer, and a temperature anisotropy (Te∥ > Te⊥) which disappeared at the field reversal. Derived scale sizes normal to the CS are: ∼6.9 de (EDR) and ∼0.4 di (IDR; 40 and 100 km). We estimate the average dimensionless reconnection rate as 0.077 ± 0.050. The observations and inferences are supported by particle-in-cell (PIC) numerical simulations. We find very good agreement in the reconnection rates. We also discuss the effects of asymmetries in the density, temperature and magnetic field strength on the Hall fields and length of the outflow jets. The event is associated with a substorm onset which began 7 min after the MMS observations. [ABSTRACT FROM AUTHOR]

Objective: Chronic uveitis is a common manifestation of pediatric rheumatologic conditions and may result in irreversible blindness and long‐term disability. While chronic anterior uveitis is the most commonly encountered ocular manifestation of rheumatic disease, little is known about the clinical presentation, management, and long‐term outcome of more complex eye conditions such as pars planitis (PP), panuveitis (PU), and Vogt‐Koyanagi‐Harada disease (VKH). The present study was undertaken to comprehensively assess the long‐term safety and efficacy of disease‐modifying antirheumatic drugs (DMARDs) and biologics for the treatment of pediatric and adolescent patients with PP, PU, and VKH. Methods: We retrospectively reviewed a cohort of 75 children and adolescents with idiopathic PP (n = 50), PU (n = 12), and VKH (n = 14) followed by the Pediatric Rheumatology Core at Children's Hospital Los Angeles and evaluated referral patterns, clinical presentation, treatment response, and long‐term clinical outcome. Results: Patients were followed for an average of 52 months. Their mean age at disease onset was 10 years. Bilateral eye involvement was seen in 87% of the patients. At first presentation to an ophthalmologist, glaucoma was noted in 21% of patients and vision loss (<20/40) in 87% of patients, while legal blindness (≤20/200 in the better‐seeing eye) was diagnosed in 18 of 75 (24%) of patients (PP 22%, PU 36%, and VKH 21%). The average referral time to a pediatric rheumatologist was 13 months (range 1–96 months). Topical steroids were used in all patients, but 98% of patients required additional DMARDs, and 73% required therapy with biologics. After a mean of 52 months, 35% of patients across all disease groups had significant vision loss or were blind, and only 28% were in clinical remission without medications. The worst outcome was observed in children with PU. Regression analysis, young age at onset, delayed referral to a pediatric rheumatologist, and chronic disease were strong predictors for the risk of long‐term blindness. Conclusion: PP, PU, and VKH involve a high risk of permanent vision loss and should be managed by a skilled rheumatologist as early and as aggressively as possible. [ABSTRACT FROM AUTHOR]

Summary: Science Gateways provide portals for experiments execution, regardless of the users' computational background. Nowadays its construction and performance need enhancement in terms of resource provision and task scheduling. We present the Modular Distributed Architecture to support the Protein Structure Prediction (MDAPSP), a Service‐Oriented Architecture for management and construction of Science Gateways, with resource provisioning on a heterogeneous environment. The Decision Maker, central module of MDAPSP, defines the best computational environment according to experiment parameters. The proof of concept for MDAPSP is presented in WorkflowSim, with two novel schedulers. Our results demonstrate good Quality of Service (QoS), capable of correctly distributing the workload, fair response times, providing load balance, and overall system improvement. The study case relies on PSP algorithms and the Galaxy framework, with monitoring experiments to show the bottlenecks and critical aspects. [ABSTRACT FROM AUTHOR]

Background and purpose: Early neurological deterioration (END) occurs in 20%–30% of patients with lacunar stroke and challenges their clinical management. This retrospective cohort study analyzed clinical and neuroimaging risk factors predicting the occurrence of END, the functional outcome after END and potential benefit from dual antiplatelet therapy (DAPT) in patients with lacunar strokes. Methods: Factors associated with END and benefit from DAPT were retrospectively analyzed in 308 patients with lacunar stroke symptoms and detected lacunar infarction by magnetic resonance imaging. END was defined by deterioration of ≥3 total National Institutes of Health Stroke Scale (NIHSS) points, ≥2 NIHSS points for limb paresis or documented deterioration within 5 days after admission. Patients were treated with DAPT according to in‐house standards. The primary efficacy end‐point for functional outcome was fulfilled if NIHSS at discharge improved after END at least to the score at admission. Results: Male gender [odds ratio (OR) 2.08; 95% confidence interval (CI) 1.09–4.00], higher age (OR = 1.65 per 10 years; 95% CI 1.18–2.31), motor paresis (OR = 18.89, 95% CI 4.66–76.57) and infarction of the internal capsule or basal ganglia (OR = 3.58, 95% CI 1.26–10.14) were associated with an increased risk for END. A larger diameter of infarction (OR = 0.85, 95% CI 0.76–0.95), more microangiopathic lesions (OR = 0.75, 95% CI 0.57–0.99) and pontine localization (OR = 0.29, 95% CI 0.12–0.65) were factors associated with unfavorable functional outcome after END occurred. Localization in the internal capsule or basal ganglia was identified as a significant predictive factor for a benefit from DAPT after END. Conclusions: Identified clinical and neuroimaging factors predicting END occurrence, functional outcome after END and potential benefit from DAPT might improve the clinical management of patients with lacunar strokes. [ABSTRACT FROM AUTHOR]

We use high‐resolution data from dayside passes of the Magnetospheric Multiscale (MMS) mission to create for the first time a comprehensive listing of encounters with the electron diffusion region (EDR), as evidenced by electron agyrotropy, ion jet reversals, and j • E′ > 0. We present an overview of these 32 EDR or near‐EDR events, which demonstrate a wide variety of observed plasma behavior inside and surrounding the reconnection site. We analyze in detail three of the 21 new EDR encounters, which occurred within a 1‐min‐long interval on 23 November 2016. The three events, which resulted from a relatively low and oscillating magnetopause velocity, exhibited large electric fields (up to ~100 mV/m), crescent‐shaped electron velocity phase space densities, large currents (≥2 μA/m2), and Ohmic heating of the plasma (~10 nW/m3). We include an Ohm's law analysis, in which we show that the divergence of the electron pressure term usually dominates the nonideal terms and is much more turbulent on the magnetosphere versus the magnetosheath side of the EDR. Plain Language Summary: NASA's Magnetospheric Multiscale (MMS) mission was designed to study magnetic reconnection, a process in which oppositely directed magnetic fields embedded within two neighboring plasma populations annihilate, dumping magnetic energy into the plasmas. Previous missions studying reconnection in space were not fully equipped to analyze how the electrons in the plasma behave near the core of a reconnection site. This study provides MMS researchers with many new reconnection events to dissect, and calls special attention to three events that occurred back to back. Each event included is very unique and helps to fill in another piece of the reconnection puzzle. Perhaps the ultimate goal of these studies is to provide insight into methods of shutting down the reconnection process, which is known to impede attempts toward a stable nuclear fusion engine. A blueprint for stable nuclear fusion could solve mankind's energy needs forever. Key Points: MMS mapped the EDR and near‐EDR several times during a sequence of new dayside encountersTurbulence in Ohm's law terms is greatest on the magnetospheric‐side EDR, near the plane containing the X line and boundary normal vectorThirty‐two EDR or near‐EDR encounters show crescent‐like enhancements in electron velocity space perpendicular to the local magnetic field [ABSTRACT FROM AUTHOR]

Objectives: This study characterizes cytogenetic abnormalities with ultrasound findings to refine counseling following negative cell-free DNA (cfDNA).Methods: A retrospective cohort of pregnancies with chromosome abnormalities and ultrasound findings was examined to determine the residual risk following negative cfDNA. Cytogenetic data was categorized as cfDNA detectable for aneuploidies of chromosomes 13, 18, 21, X, or Y or non-cfDNA detectable for other chromosome abnormalities. Ultrasound reports were categorized as structural anomaly, nuchal translucency (NT) ≥3.0 mm, or other "soft markers". Results were compared using chi squared and Fishers exact tests.Results: Of the 498 fetuses with cytogenetic abnormalities and ultrasound findings, 16.3% (81/498) had non-cfDNA detectable results. In the first, second, and third trimesters, 12.4% (32/259), 19.5% (42/215), and 29.2% (7/24) had non-cfDNA detectable results respectively. The first trimester non-cfDNA detectable results reduced to 7.7% (19/246) if triploidy was detectable by cfDNA testing. For isolated first trimester NT of 3.0-3.49 mm, 15.8% (6/38) had non-cfDNA detectable results, while for NT ≥3.5 mm, it was 12.3% (20/162). For cystic hygroma, 4.3% (4/94) had non-cfDNA detectable results.Conclusions: Counseling for residual risk following cfDNA in the presence of an ultrasound finding is impacted by gestational age, ultrasound finding, and cfDNA detection of triploidy. [ABSTRACT FROM AUTHOR]

The growth of real-world objects with embedded and globally networked sensors allows to consolidate the Internet of things paradigm and increase the number of applications in the domains of ubiquitous and context-aware computing. The merging between cloud computing and Internet of things named cloud of things will be the key to handle thousands of sensors and their data. One of the main challenges in the cloud of things is context-aware sensor search and selection. Typically, sensors require to be searched using two or more conflicting context properties. Most of the existing work uses some kind of multi-criteria decision analysis to perform the sensor search and selection, but does not show any concern for the quality of the selection presented by these methods. In this paper, we analyse the behaviour of the SAW, TOPSIS and VIKOR multi-objective decision methods and their quality of selection comparing them with the Pareto-optimality solutions. The gathered results allow to analyse and compare these algorithms regarding their behaviour, the number of optimal solutions and redundancy. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to compare the gestational age at termination for trisomy 13, 18, or 21 (aneuploidy) before and after the introduction of noninvasive prenatal testing (NIPT).Methods: A retrospective cohort of women undergoing termination for aneuploidy at two academic institutions and one private clinic. We compared two time periods: before and after the introduction of NIPT (2006-2011 and 2012-2014, respectively). Maternal demographics and clinical characteristics were abstracted from the medical record. Nonparametric statistical methods were used to compare the two cohorts.Results: Our cohort included 93 women: 41 prior to NIPT and 52 post-NIPT. Maternal age (38 post-NIPT vs 37 pre-NIPT; p = 0.17) did not differ between the time periods. Women in the post-NIPT were less likely to undergo diagnostic testing (82.7% vs 97.6%; p < 0.01) before proceeding to abortion after a positive screening result. In the post-NIPT period, there was a significant decrease in the gestational age at time of invasive testing (13.0 vs 15.7 weeks; p < 0.01) and women were more likely to undergo chorionic villous sampling (CVS) (59.6% vs 41.5%; p < 0.01). There was a significant decrease in the gestational age at termination (14.2 vs 17.2; p < 0.01). Women in the post-NIPT group were less likely to have terminations after 16 weeks (25.0% vs 61.0%; p < 0.01), 18 weeks (7.7% vs 39.0%; p < 0.01), or 20 weeks (3.9% vs 12.2%; p = 0.23).Conclusion: With the introduction of NIPT, the median gestational age at diagnosis and termination for women with Trisomy 13, 18, or 21 was 3 weeks earlier. Women were four times less likely to have a termination after 18 weeks and three times less likely to have a termination after 20 weeks. © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: Evaluate patient choices and outcomes following positive cfDNA.Method: Retrospective cohort study of women with positive cfDNA through two academic centers between March 2012 and December 2014. Patients were screened based on ACOG indications. Medical records reviewed for counseling, ultrasound findings, diagnostic testing, karyotype and outcome.Results: CfDNA was positive in 114 women; 105 singletons and 9 twin pairs. CfDNA was positive for autosomal trisomy (21, 18, 13) in 96 (84.2%) and sex chromosome aneuploidy in 18 (15.8%). Certified genetic counselors performed 95% of post-cfDNA counseling. Prenatal diagnostic testing was pursued by 71/114 (62%). Karyotype was available in 91/105 (86.7%) singletons and confirmed aneuploidy in 75/91 (82.4%); the PPV of cfDNA with any ultrasound finding was 93.6% versus 58.6% without a finding. An abnormal sonographic finding was seen in 4/16 (25%) singletons with false positive cfDNA. Fetal termination occurred in 53/79 (67%) singletons and 3/5 (60%) twins with prenatal abnormal or unknown karyotype for autosomal trisomy. Eleven fetuses (11/56, 19.6%) were terminated for suspected autosomal trisomy without karyotype confirmation.Conclusion: Patient choices following positive cfDNA are varied. Ultrasound modifies the PPV of cfDNA. Termination rates for aneuploidy are not higher than historical controls. Recommendation for karyotype confirmation prior to termination is not universally followed. © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine the role of the 11- to 14-week ultrasound in women with negative cell-free DNA screening.Methods: A retrospective cohort study of women at increased risk for aneuploidy based on age or medical history and negative cell-free DNA screening between March 2012 and March 2014 was conducted. Patients were included if they had an 11- to 14-week ultrasound and obstetrical care at our center(s). Primary outcome was an unexpected finding at ultrasound. Imaging findings were compared with obstetrical outcome by medical record review.Results: Study group was composed of 1739 patients. An unexpected finding was identified in 60/1739 (3.5%). An abnormal fetal finding occurred in 37 living fetuses (2.1%); 33 had a nuchal translucency (NT) ≥ 3 mm, including four 'isolated' cystic hygroma and three with a structural abnormality. Four fetuses had a structural anomaly without a thick NT. Karyotype confirmed euploidy in 98.7% of available cases. Pregnancy termination was chosen by 63.6% of those with cystic hygroma or anomaly at the 11- to 14-week scan. Unexpected multiples were identified in 13 (0.7%) women and a fetal demise in 10 (0.6%).Conclusion: Unexpected findings at the 11- to 14-week scan occur in 3.5% of patients with negative cell-free DNA. Recognition provides options for comprehensive testing, consultation, and management. [ABSTRACT FROM AUTHOR]

Background: Digital smartphone assistants for the care and support of people with dementia (PwD) have great potential due to the wide availability of smartphones and a growing number of users aged above 65. Research has mainly focused on the development of applications for only one user group (patients, caregivers, or relatives respectively), and with only one or a few functions included (Yousaf et al., 2020). A more integrative, multi‐user, and multifunctional application would be beneficial because it could be adapted to the users' needs more flexibly. This qualitative interview study was the first step in a co‐creative process with a user‐centered approach aimed at developing a multifunctional digital assistant. Method: Qualitative content analysis (Mayring, 2010) combining deductive and inductive techniques was applied to identify burdens, needs, functions, ethical considerations, and acceptance aspects. 14 semi‐structured interviews were conducted with three participant groups (relatives of PwD; caregivers and nursing staff; psychologists). Interviews were conducted via video conferences due to Covid‐19 restrictions. After the completion of all interviews, participants received several questionnaires on acceptance aspects (Technology Usage Inventory [TUI], acceptance rating of specific functions), and technological affinity (TA‐EG questionnaire) via letter. Interviews were transcribed verbatim with the software MAXQDA. Coding was done by two independent researchers. A coding frame was generated using the interview guide as a theoretical basis and the collected data for building inductive categories. The coding frame was pilot‐tested before the final analysis and intercoder reliability was sufficient (k=.81). Result: Preliminary results showed that dealing with symptoms of dementia in everyday life was burdening. Emotional needs in patients and needs for additional care resources in relatives and caregivers were the most important unanswered needs. 53 functions were suggested in the areas: digital care, support, training, monitoring, navigation, leisure activities, and social contacts. Participants had ethical requirements (i.e. data protection, privacy, and autonomy) that if met, would enhance acceptance. Results on questionnaires showed positive attitudes towards, curiosity about, and no insecurity with regards to technology. The overall acceptability of suggested functions was high. Conclusion: Participants showed a large interest in the digital assistant. The importance of data protection was underlined. [ABSTRACT FROM AUTHOR]

Objective: Transition from pediatric to adult care is a complex process and can negatively impact patients with chronic disease. We describe the transition experience of patients with pediatric-onset systemic lupus erythematosus (SLE) and its associated outcomes in adulthood.Methods: A telephone survey of 41 pediatric-onset SLE patients was conducted following their transition to adult care. Data on medical and social outcomes during and after the transition were collected. Health status was compared to retrospectively collected baseline data at pediatric discharge.Results: The mean ± SD followup interval was 5 ± 3.7 years; the mean ± SD age at followup was 24 ± 4.2 years. More than half of patients (22 of 41) experienced transition difficulties, primarily due to loss of insurance and emotional readjustment, which were associated with poor symptom control (P = 0.03) and multiple organ system involvement (P = 0.05) at followup. After the transition, most patients (35 of 41) were followed by an adult-care rheumatologist, and the majority (37 of 41) reported recent symptoms of active disease; 41% (13 of 29) had developed symptoms suggestive of new renal manifestations following transition. One-third (15 of 41) reported new or ongoing neuropsychiatric symptoms. Both renal and neuropsychiatric manifestations were associated with unemployment (P < 0.05). Direct referral by a pediatric rheumatologist was associated with fewer hospitalizations following transition (P = 0.04).Conclusion: The majority of patients transitioned successfully to adult rheumatologic care. Major challenges were loss of insurance and attachment to pediatric providers, highlighting the importance of a structured transition process that focuses on providing emotional and financial guidance. Disease activity in pediatric-onset SLE remains high throughout adulthood, with morbidity primarily related to renal and neuropsychiatric manifestations. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to examine mothers' experiences with chromosomal microarray analysis ( CMA) for a child with autism spectrum disorder ( ASD). Design and Methods This is a descriptive qualitative study using thematic content analysis of in-depth interview with 48 mothers of children who had genetic testing for ASD. Results The principal theme, 'something is missing,' included missing knowledge about genetics, information on use of the results, explanations of the relevance to the diagnosis, and relevance to life-long care. Two subordinate themes were (a) disappreciation of the helpfulness of scientific information to explain the diagnosis, and (b) returning to personal experience for interpretation. Practice Implications The test 'appreciated' in value when results could be linked to the phenotype. [ABSTRACT FROM AUTHOR]

The intestinal epithelium is remarkably robust despite perturbations and demand uncertainty. Here, we investigate the basis of such robustness using novel tracing methods that allow simultaneously capturing the dynamics of stem and committed progenitor cells (called enteroblasts) and intestinal cell turnover with spatiotemporal resolution. We found that intestinal stem cells ( ISCs) divide 'ahead' of demand during Drosophila midgut homeostasis. Their newborn enteroblasts, on the other hand, take on a highly polarized shape, acquire invasive properties and motility. They extend long membrane protrusions that make cell-cell contact with mature cells, while exercising a capacity to delay their final differentiation until a local demand materializes. This cellular plasticity is mechanistically linked to the epithelial-mesenchymal transition ( EMT) programme mediated by escargot, a snail family gene. Activation of the conserved micro RNA miR-8/miR-200 in 'pausing' enteroblasts in response to a local cell loss promotes timely terminal differentiation via a reverse MET by antagonizing escargot. Our findings unveil that robust intestinal renewal relies on hitherto unrecognized plasticity in enteroblasts and reveal their active role in sensing and/or responding to local demand. [ABSTRACT FROM AUTHOR]

Objective To determine the dose of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood-onset systemic lupus erythematosus (SLE) who require cyclophosphamide therapy, to determine the length of time needed to achieve ovarian suppression after initiation of triptorelin treatment, and to investigate the safety of triptorelin. Methods In this randomized, double-blind, placebo-controlled, dose-escalation study, female patients ages <21 years were randomized 4:1 to receive triptorelin (n = 25) or placebo (n = 6). The starting doses of triptorelin were 25, 50, 75, and 100 μg/kg, and the dose was escalated until complete ovarian suppression was maintained. The primary outcome was the weight-adjusted dose of triptorelin that provided complete ovarian suppression in at least 90% of the patients, as determined by gonadotropin-releasing hormone agonist stimulation testing. The secondary outcome was the period of time required to achieve ovarian suppression, as measured by unstimulated follicle-stimulating hormone and luteinizing hormone levels after the initiation of triptorelin treatment. Results Treatment with triptorelin at a weight-adjusted dose of 120 μg/kg body weight provided sustained complete ovarian suppression in 90% of the patients. After administration of the initial dose of triptorelin, 22 days were required to achieve complete ovarian suppression. The rates of adverse events (AEs) and serious adverse events (SAEs) per 100 patient-months of followup were not higher in the triptorelin group compared with the placebo group (for AEs, 189 versus 362; for SAEs, 2.1 versus 8.5). Conclusion High doses of triptorelin are needed to achieve and maintain complete ovarian suppression, but such doses appear to be well tolerated in adolescent female patients with childhood-onset SLE. Our data suggest that a lag time of 22 days after initiation of triptorelin treatment is required before cyclophosphamide therapy is started or continued. [ABSTRACT FROM AUTHOR]

The utilization of genome-wide chromosomal microarray analysis (CMA) in pediatric clinical practice provides an opportunity to consider how genetic diagnostics is evolving, and to prepare for the clinical integration of genome-wide sequencing technologies. We conducted semi-structured interviews with 15 healthcare providers (7 genetic counselors, 4 medical geneticists, and 4 non-genetics providers) to investigate the impact of CMA on clinical practice, and implications for providers, patients and families. Interviews were analyzed qualitatively using content analysis. Most providers reported that genomic testing enhanced their professional experience and was beneficial to patients, primarily due to the improved diagnostic rate compared with earlier chromosomal studies. Other effects on practice included moving towards genotype-first diagnosis and broadening indications for chromosomal testing. Opinions varied concerning informed consent and disclosure of results. The duty to disclose incidental findings (IFs) was noted; however concerns were raised about potential psychosocial harms of disclosing pre-symptomatic findings. Tensions were revealed between the need for comprehensive informed consent for all families and the challenges of communicating time-consuming and potentially anxiety-provoking information regarding uncertain and incidental findings that may be relevant only in rare cases. Genetic counselors can play an important role in liaising with families, health professionals and testing laboratories, providing education and guidance to non-genetics providers, and enabling families to receive adequate pre-and post-test information and follow-up care. [ABSTRACT FROM AUTHOR]

Objectives This study was intended to determine if previously identified educational benefits of the Harvard Medical School ( HMS) Cambridge Integrated Clerkship ( CIC) endure over time. Methods The authors' earlier work compared the 27 graduates in the first three cohorts of students undertaking the CIC with a comparison group of 45 traditionally trained HMS students; CIC graduates emerged from their clerkship year with a higher degree of patient-centredness and felt more prepared to deal with numerous domains of patient care. Between April and July 2011, at 4-6 years post-clerkship, the authors asked these original study cohorts to complete an electronic survey which included measures used in the original study. The authors also reviewed data from the National Residency Match Program to compare career paths in the two groups. Results The response rate was 62% (42/68). The immediate post-clerkship finding that CIC students held more patient-centred attitudes was sustained over time (p < 0.035). Reflecting retrospectively on their clerkship experiences, CIC graduates continued to report that their clerkship year had better prepared them in a wide variety of domains. Graduates of the CIC attained awards and published papers at the same rates as peers, and were more likely to engage in health advocacy work. Both groups chose a wide range of residency programmes. Among those expressing a preference, no CIC graduates said they would choose a traditional clerkship, but 6 (27%) of the traditionally trained graduates said they would choose a longitudinal integrated clerkship. Conclusions This paper indicates that benefits of longitudinal integrated clerkship training are sustained over time across multiple domains. [ABSTRACT FROM AUTHOR]

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Objective To determine the long-term safety and efficacy of rilonacept, an anti-interleukin-1 fusion protein, in patients with active systemic juvenile idiopathic arthritis (JIA). Methods In patients with systemic JIA, ages 4-20 years, the efficacy of rilonacept was evaluated using 30%, 50%, and 70% levels of improvement according to the adapted American College of Rheumatology (ACR) Pediatric 30, 50, and 70 response criteria, respectively. Efficacy and safety were evaluated during 23 months of open-label treatment (3 phases) after a 4-week, double-blind, placebo-controlled phase. Following double-blind treatment with 2.2 mg/kg or 4.4 mg/kg of rilonacept, patients were eligible to receive open-label treatment at their prior dose, with adjustments. Reductions in the median daily dose of oral prednisone and improvements in laboratory parameters of disease activity (i.e., decreased levels of D-dimer and myeloid-related proteins [MRPs]) were also evaluated. Results Twenty-four patients entered the double-blind study and 23 entered the open-label period. Patients were predominantly white and female, and had a median age of 14.0 years at baseline. No significant differences in efficacy were observed between the rilonacept- and placebo-treated patients during the double-blind phase, but fever and rash completely resolved by month 3 in all patients during the open-label treatment period and did not recur. Adapted ACR Pediatric 30, 50, and 70 response rates at 3 months from the start of the study were 78.3%, 60.9%, and 34.8%, respectively; these responses were generally maintained over the study duration. Levels of D-dimer and MRP-8/MRP-14 dramatically improved during the study, and in 22 of 23 patients, the prednisone dose was decreased or prednisone therapy was discontinued. No serious treatment-related adverse events were observed. Conclusion Sustained improvements in clinical and laboratory measures of the articular and systemic manifestations of systemic JIA were achieved in >50% of rilonacept-treated patients over 2 years. Treatment with rilonacept had a substantial steroid-sparing effect and was generally well-tolerated. [ABSTRACT FROM AUTHOR]

Chromosomal microarray analysis ( CMA) has improved the diagnostic rate of genomic disorders in pediatric populations, but can produce uncertain and unexpected findings. This article explores clinicians' perspectives and identifies challenges in effectively interpreting results and communicating with families about CMA. Responses to an online survey were obtained from 40 clinicians who had ordered CMA. Content included practice characteristics and perceptions, and queries about a hypothetical case involving uncertain and incidental findings. Data were analyzed using nonparametric statistical tests. Clinicians' comfort levels differed significantly for explaining uncertain, abnormal, and normal CMA results, with lowest levels for uncertain results. Despite clinical guidelines recommending informed consent, many clinicians did not consider it pertinent to discuss the potential for CMA to reveal information concerning biological parentage or predisposition to late-onset disease, in a hypothetical case. Many non-genetics professionals ordering CMA did not feel equipped to interpret the results for patients, and articulated needs for education and access to genetics professionals. This exploratory study highlights key challenges in the practice of genomic medicine, and identifies needs for education, disseminated practice guidelines, and access to genetics professionals, especially when dealing with uncertain or unexpected findings. [ABSTRACT FROM AUTHOR]