Tag: pubmed

Proc Natl Acad Sci U S A. 2021 Aug 3;118(31):e2022518118. doi: 10.1073/pnas.2022518118.

ABSTRACT

The observational absence of giant convection cells near the Sun’s outer surface is a long-standing conundrum for solar modelers. We herein propose an explanation. Rotation strongly influences the internal dynamics, leading to suppressed convective velocities, enhanced thermal-transport efficiency, and (most significantly) relatively smaller dominant length scales. We specifically predict a characteristic convection length scale of roughly 30-Mm throughout much of the convection zone, implying weak flow amplitudes at 100- to 200-Mm giant cells scales, representative of the total envelope depth. Our reasoning is such that Coriolis forces primarily balance pressure gradients (geostrophy). Background vortex stretching balances baroclinic torques. Both together balance nonlinear advection. Turbulent fluxes convey the excess part of the solar luminosity that radiative diffusion cannot. We show that these four relations determine estimates for the dominant length scales and dynamical amplitudes strictly in terms of known physical quantities. We predict that the dynamical Rossby number for convection is less than unity below the near-surface shear layer, indicating rotational constraint.

PMID:34326248 | DOI:10.1073/pnas.2022518118

RMD Open. 2021 Jul;7(2):e001710. doi: 10.1136/rmdopen-2021-001710.

ABSTRACT

OBJECTIVE: Non-pharmacological interventions support patients with connective tissue diseases to better cope with and self-manage their diseases. This study aimed to map existing evidence on non-pharmacological interventions in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and mixed connective tissue diseases regarding content, feasibility and potential suitability in an e-health setting.

METHODS: A literature search was performed in eight different databases in July 2020. The intervention’s content was extracted using the ‘Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide’. A Sankey diagram and descriptive statistics were used to analyse the data and illustrate the relationships between the interventions.

RESULTS: Of 8198 identified records, 119 papers were eligible. One hundred and four of them (87.4%) were conducted between 2000 and 2020, mainly in the USA (SLE n=24 (21.2%), SSc n=16 (14.2%)), Brazil (SLE n=8 (7.1%), SSc n=5 (4.4%)) and Italy (SLE n=0 (0%), SSc n=12 (10.6%)). Fifty-two studies (SLE n=24 (21.2%), SSc n=28 (24.8%)) used multicomponent interventions. The single interventions were physical exercises (SLE n=16 (14.2%), SSc n=17 (15.0%)), coaching/counselling (SLE n=11 (18.0%), SSc n=0 (0%)) and education (SLE n=2 (1.8%), SSc n=3 (2.7%)). Primary outcomes focused on physical function (SLE n=1 (0.9%), SSc n=15 (13.3%)), mouth opening in SSc (n=4 (5.9%)) and physical capacity (SLE n=2 (1.8%), SSc n=1 (0.9%)). No interventions for mixed connective tissue disease were found.

CONCLUSION: There was a great variety in the intervention’s content due to differences in body structure, activity limitations and participation restrictions in SLE and SSc. These results highlight the need for personalised, multicomponent, non-pharmacological interventions, which could be delivered as e-health interventions.

PMID:34326205 | DOI:10.1136/rmdopen-2021-001710

Proc Natl Acad Sci U S A. 2021 Aug 3;118(31):e2020402118. doi: 10.1073/pnas.2020402118.

ABSTRACT

To mimic the mechanical response of passive biological cilia in complex fluids, we study the bending dynamics of an anchored elastic fiber submitted to a dilute granular suspension under shear. We show that the bending fluctuations of the fiber accurately encode minute variations of the granular suspension concentration. Indeed, besides the stationary bending induced by the continuous phase flow, the passage of each single particle induces an additional deflection. We demonstrate that the dominant particle/fiber interaction arises from contacts of the particles with the fiber, and we propose a simple elastohydrodynamics model to predict their amplitude. Our results provide a mechanistic and statistical framework to describe particle detection by biological ciliated systems.

PMID:34326246 | DOI:10.1073/pnas.2020402118

J Immunother Cancer. 2021 Jul;9(7):e002851. doi: 10.1136/jitc-2021-002851.

ABSTRACT

BACKGROUND: The modified Glasgow Prognostic Score (mGPS) is a composite biomarker that uses albumin and C reactive protein (CRP). There are multiple immune checkpoint inhibitor (ICI)-based combinations approved for metastatic renal cell carcinoma (mRCC). We investigated the ability of mGPS to predict outcomes in patients with mRCC receiving ICI.

METHODS: We retrospectively reviewed patients with mRCC treated with ICI as monotherapy or in combination at Winship Cancer Institute between 2015 and 2020. Overall survival (OS) and progression-free survival (PFS) were measured from the start date of ICI until death or clinical/radiographical progression, respectively. The baseline mGPS was defined as a summary score based on pre-ICI values with one point given for CRP>10 mg/L and/or albumin<3.5 g/dL, resulting in possible scores of 0, 1 and 2. If only albumin was low with a normal CRP, no points were awarded. Univariate analysis (UVA) and multivariate analysis (MVA) were carried out using Cox proportional hazard model. Outcomes were also assessed by Kaplan-Meier analysis.

RESULTS: 156 patients were included with a median follow-up 24.2 months. The median age was 64 years and 78% had clear cell histology. Baseline mGPS was 0 in 36%, 1 in 40% and 2 in 24% of patients. In UVA, a baseline mGPS of 2 was associated with shorter OS (HR 4.29, 95% CI 2.24 to 8.24, p<0.001) and PFS (HR 1.90, 95% CI 1.20 to 3.01, p=0.006) relative to a score of 0; this disparity in outcome based on baseline mGPS persisted in MVA. The respective median OS of patients with baseline mGPS of 0, 1 and 2 was 44.5 (95% CI 27.3 to not evaluable), 15.3 (95% CI 11.0 to 24.2) and 10 (95% CI 4.6 to 17.5) months (p<0.0001). The median PFS of these three cohorts was 6.7 (95% CI 3.6 to 13.1), 4.2 (95% CI 2.9 to 6.2) and 2.6 (95% CI 2.0 to 5.6), respectively (p=0.0216). The discrimination power of baseline mGPS to predict survival outcomes was comparable to the IMDC risk score based on Uno’s c-statistic (OS: 0.6312 vs 0.6102, PFS: 0.5752 vs 0.5533).

CONCLUSION: The mGPS is prognostic in this cohort of patients with mRCC treated with ICI as monotherapy or in combination. These results warrant external and prospective validation.

PMID:34326170 | DOI:10.1136/jitc-2021-002851

Eur Respir J. 2021 Jul 29:2003969. doi: 10.1183/13993003.03969-2020. Online ahead of print.

ABSTRACT

BACKGROUND: Asthma is a heterogeneous syndrome substantiating the urgent requirement for endotype-specific biomarkers. Dysbalance of fibrosis and fibrolysis in asthmatic lung tissue leads to reduced levels of the inflammation-protective collagen 4 (COL4A3).

OBJECTIVE: To delineate the degradation of COL4A3 in allergic airway inflammation and evaluate the resultant product as a biomarker for anti-IgE therapy response.

METHODS: The serological COL4A3 degradation marker C4Ma3 (Nordic Bioscience, Denmark) and serum cytokines were measured in the ALLIANCE cohort (pediatric cases/controls: 134/35; adult cases/controls: 149/31). Exacerbation of allergic airway disease in mice was induced by sensitising to OVA, challenge with OVA aerosol and instillation of poly(cytidylic-inosinic). Fulacimstat (chymase inhibitor, Bayer) was used to determine the role of mast cell chymase in COL4A3 degradation. Patients with cystic fibrosis (CF, n=14) and CF with allergic broncho-pulmonary aspergillosis (ABPA, n=9) as well as severe allergic, uncontrolled asthmatics (n=19) were tested for COL4A3 degradation. Omalizumab (anti-IgE) treatment was assessed by the Asthma Control Test.

RESULTS: Serum levels of C4Ma3 were increased in asthma in adults and children alike and linked to a more severe, exacerbating allergic asthma phenotype. In an experimental asthma mouse model, C4Ma3 was dependent on mast cell chymase. Serum C4Ma3 was significantly elevated in CF plus ABPA and at baseline predicted the success of the anti-IgE therapy in allergic, uncontrolled asthmatics (diagnostic odds ratio 31.5).

CONCLUSION: C4Ma3 level depend on lung mast cell chymase and are increased in a severe, exacerbating allergic asthma phenotype. C4Ma3 may serve as a novel biomarker to predict anti-IgE therapy response.

PMID:34326188 | DOI:10.1183/13993003.03969-2020

BMJ Open Respir Res. 2021 Jul;8(1):e000805. doi: 10.1136/bmjresp-2020-000805.

ABSTRACT

BACKGROUND AND OBJECTIVE: A high frequency of infections complicating rheumatoid arthritis (RA) has been reported due to the immunomodulatory effect of RA or to agents with immunosuppressive effects used in its treatment. We aimed to assess clinical and radiological characteristics of pulmonary cryptococcosis in patients with and without RA.

METHODS: We retrospectively reviewed the medical records of 52 patients with pulmonary cryptococcosis and divided them into two groups, those with RA and without RA, and compared clinical characteristics and radiological findings between them.

RESULTS: Eleven (21.2%) of the 52 patients had RA. Median follow-up periods were 51.2 (range: 1.1-258.7) months for patients with RA and 19.1 (range: 0.63-246.9) months for patients without RA. Among the patients with RA, 81.8% were women, with a mean age of 68.1 years. Female sex and respiratory comorbidities were significantly more frequent in patients with RA than in patients without RA. Frequencies of concomitant cryptococcal meningitis and respiratory failure were not different between the groups. There were no significant differences in frequency of any radiological findings, locations and number between the two groups. Among patients with RA, all but one responded well to antifungal treatment. During the antifungal treatment course, one (9.1%) patient with RA died of cryptococcosis. Despite continuing antirheumatic drugs, no patients had recurrence of pulmonary cryptococcosis during follow-up.

CONCLUSION: Other than some differences in background, there were no clinical, radiological or prognostic differences between the patients with and without RA with pulmonary cryptococcosis. The administration of antirheumatic therapy had no negative effect on the clinical course of antifungal treatment.

PMID:34326152 | DOI:10.1136/bmjresp-2020-000805

BMJ Open Respir Res. 2021 Jul;8(1):e000918. doi: 10.1136/bmjresp-2021-000918.

ABSTRACT

Lung volume recruitment manoeuvres are often prescribed to maintain respiratory health in neuromuscular disease. Unfortunately, no current system accurately records delivered dose. This study determined the performance characteristics of a novel, objective, manual lung volume recruitment bag counter (‘the counter’) with bench and healthy volunteer testing, as well as in individuals with neuromuscular disease. We undertook (1) bench test determination of activation threshold, (2) bench and healthy volunteer fidelity testing during simulated patient interface leak and different pressure compressions and (3) comparisons with self-report in individuals with neuromuscular disease. The data are reported as summary statistics, compression counts, percentage of recorded versus delivered compressions and concordance (Cohen’s kappa (K) and absolute agreement). RESULTS: Minimum counter activation pressure under conditions of zero leak was 1.9±0.4 cm H₂O. No difference was observed between the number of repetitions delivered and recorded during high airway pressure condition. Interface leak approximating 25% resulted in underestimation of repetition counts, and once the leak was at 50% or beyond, the counter recorded no activity. Faster sampling frequency collected data with more fidelity. Counter data agreed with diary self-report during community trials (16 participants, 960 participant days, 77% agreement, Cohen’s Κ=0.66 and p<0.001). Disagreement typically favoured more diary reported (18%) than counter (5%) sessions. CONCLUSIONS: The performance characteristics of a new lung volume recruitment counter have been established in both laboratory and community settings. Objective usage and dosage data should accelerate new knowledge development and better translation of lung volume recruitment therapy into policy and practice.

PMID:34326156 | DOI:10.1136/bmjresp-2021-000918

BJGP Open. 2021 Jul 29:BJGPO.2021.0051. doi: 10.3399/BJGPO.2021.0051. Online ahead of print.

ABSTRACT

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease which causes painful discharging nodules and skin tunnels. HS has associations with several systemic diseases, including cardiovascular (CV) disease and anxiety-depression. High levels of chronic morbidity suggest an important role for Primary Care. However, little evidence exists regarding current management of HS and its co-morbidities in UK General Practice.

AIM: To describe current practice amongst UK GPs in treating and referring people with HS DESIGN & SETTING: Web-based survey circulated to UK Primary Care Dermatology Society members and GPs in Forth Valley, Scotland.

METHOD: Survey responses were analysed with descriptive statistics.

RESULTS: 134 UK GPs completed the survey. 71% (n=94) saw at least one patient with HS in the previous month. 94% (n=125) reported confidence in diagnosis, and 87% (n=120) in initial treatment of HS. Most GPs initiated topical treatments and extended courses of oral antibiotic for HS, and many advised regarding adverse lifestyle factors. A minority provided analgesia, or screening for CV disease risk factors and anxiety-depression. Most GPs referred to Dermatology if Secondary Care input was required, with few referrals to specialised multi-disciplinary services.

CONCLUSION: GPs regularly diagnose and manage uncomplicated HS, but screening for important co-morbidities associated with HS is not common practice.

PMID:34326099 | DOI:10.3399/BJGPO.2021.0051

AJNR Am J Neuroradiol. 2021 Jul 29. doi: 10.3174/ajnr.A7236. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Noninvasive angiography is commonly used to assess the outcome of surgical or endovascular treatment of intracranial aneurysms in clinical series or randomized trials. We sought to assess whether a standardized 3-grade classification system could be reliably used to compare the CTA and MRA results of both treatments.

MATERIALS AND METHODS: An electronic portfolio composed of CTAs of 30 clipped and MRAs of 30 coiled aneurysms was independently evaluated by 24 raters of diverse experience and training backgrounds. Twenty raters performed a second evaluation 1 month later. Raters were asked which angiographic grade and management decision (retreatment; close or long-term follow-up) would be most appropriate for each case. Agreement was analyzed using the Krippendorff α (α_K) statistic, and the relationship between angiographic grade and clinical management choice, using the Fisher exact and Cramer V tests.

RESULTS: Interrater agreement was substantial (α_K = 0.63; 95% CI, 0.55-0.70); results were slightly better for MRA results of coiling (α_K = 0.69; 95% CI, 0.56-0.76) than for CTA results of clipping (α_K = 0.58; 95% CI, 0.44-0.69). Intrarater agreement was substantial to almost perfect. Interrater agreement regarding clinical management was moderate for both clipped (α_K = 0.49; 95% CI, 0.32-0.61) and coiled subgroups (α_K = 0.47; 95% CI, 0.34-0.54). The choice of clinical management was strongly associated with the size of the residuum (mean Cramer V = 0.77 [SD, 0.14]), but complete occlusions (grade 1) were followed more closely after coiling than after clipping (P = .01).

CONCLUSIONS: A standardized 3-grade scale was found to be a reliable and clinically meaningful tool to compare the results of clipping and coiling of aneurysms using CTA or MRA.

PMID:34326106 | DOI:10.3174/ajnr.A7236

J Neurosci. 2021 Jul 29:JN-RM-2459-20. doi: 10.1523/JNEUROSCI.2459-20.2021. Online ahead of print.

ABSTRACT

Many decisions, from crossing a busy street to choosing a profession, require integration of discrete sensory events. Previous studies have shown that integrative decision-making favours more reliable stimuli, mimicking statistically optimal integration. It remains unclear, however, whether reliability biases operate even when they lead to suboptimal performance. To address this issue, we asked human observers to reproduce the average motion direction of two suprathreshold coherent motion signals presented successively and with varying levels of reliability, while simultaneously recording whole-brain activity using electroencephalography. By definition, the averaging task should engender equal weighting of the two component motion signals, but instead we found robust behavioural biases in participants’ average decisions that favoured the more reliable stimulus. Using population-tuning modelling of brain activity we characterised tuning to the average motion direction. In keeping with the behavioural biases, the neural tuning profiles also exhibited reliability biases. A control experiment revealed that observers were able to reproduce motion directions of low-and high-reliability with equal precision, suggesting that unbiased integration in this task was not only theoretically optimal but demonstrably possible. Our findings reveal that temporal integration of discrete sensory events in the brain is automatically and sub-optimally weighted according to stimulus reliability.Significance statement:Many everyday decisions require integration of several sources of information. To safely cross a busy road, for example, one must consider the movement of vehicles with different speeds and trajectories. Previous research has shown that individual stimuli are weighted according to their reliability. Whereas reliability biases typically yield performance that closely mimic statistically optimal integration, it remains unknown whether such biases arise even when they lead to suboptimal performance. Here we combined a novel integrative decision-making task with concurrent brain recording and modelling to address this question. While unbiased decisions were optimal in the task, observers nevertheless exhibited robust reliability biases in both behaviour and brain activity, suggesting that reliability-weighted integration is automatic and dissociable from statistically optimal integration.

PMID:34326142 | DOI:10.1523/JNEUROSCI.2459-20.2021