Dyspnoea perception during clinical remission of atopic asthma

Symptoms of atopic asthma often disappear around puberty. The authors recently demonstrated that this clinical remission is accompanied with ongoing airways inflammation in most subjects. The discrepancy between lack of symptoms and persistent airway inflammation suggests that perception of the symptoms is unclear. In the present study, young adults in clinical remission of atopic asthma assigned themselves a modified Borg score during methacholine and adenosine-5'-monophosphate induced bronchoconstriction. Borg scores of subjects in clinical remission were compared with those of symptomatic asthmatic subjects. A marked variation in the Borg scores at a 20% fall in the forced expiratory volume in one second was found. Significant differences in Borg scores between remission patients and asthmatics could not be detected. It was concluded that perception of dyspnoea, induced with methacholine and adenosine challenge, is similar in young adults in clinical remission of atopic asthma compared to that of patients with symptomatic asthma. Hence, an unclear perception seems to be an unlikely explanation for the discrepancy between lack of symptoms and ongoing inflammation. Other factors, including both physical and psychological ones, may play a role in the apparent absence of symptoms, thereby potentially leading to undertreatment

Simulating an integrated critiquing system

OBJECTIVE: To investigate factors that determine the feasibility and effectiveness of a critiquing system for asthma/COPD that will be integrated with a general practitioner's (GP's) information system. DESIGN: A simulation study. Four reviewers, playing the role of the computer, generated critiquing comments and requests for additional information on six electronic medical records of patients with asthma/COPD. Three GPs who treated the patients, playing users, assessed the comments and provided missing information when requested. The GPs were asked why requested missing information was unavailable. The reviewers reevaluated their comments after receiving requested missing information. MEASUREMENTS: Descriptions of the number and nature of critiquing comments and requests for missing information. Assessment by the GPs of the critiquing comments in terms of agreement with each comment and judgment of its relevance, both on a five-point scale. Analysis of causes for the (un-)availability of requested missing information. Assessment of the impact of missing information on the generation of critiquing comments. RESULTS: Four reviewers provided 74 critiquing comments on 87 visits in six medical records. Most were about prescriptions (n = 28) and the GPs' workplans (n = 27). The GPs valued comments about diagnostics the most. The correlation between the GPs' agreement and relevance scores was 0.65. However, the GPs' agreements with prescription comments (complete disagreement, 31.3%; disagreement, 20.0%; neutral, 13.8%; agreement, 17.5%; complete agreement, 17.5%) differed from their judgments of these comments' relevance (completely irrelevant, 9.0%; irrelevant, 24.4%; neutral, 24.4%; relevant, 32.1%; completely relevant, 10.3%). The GPs were able to provide answers to 64% of the 90 requests for missing information. Reasons available information had not been recorded were: the GPs had not recorded the information explicitly; they had assumed it to be common knowledge; it was available elsewhere in the record. Reasons information was unavailable were: the decision had been made by another; the GP had not recorded the information. The reviewers left 74% of the comments unchanged after receiving requested missing information. CONCLUSION: Human reviewers can generate comments based on information currently available in electronic medical records of patients with asthma/COPD. The GPs valued comments regarding the diagnostic process the most. Although they judged prescription comments relevant, they often strongly disagreed with them, a discrepancy that poses a challenge for the presentation of critiquing comments for the future critiquing system. Requested additional information that was provided by the GPs led to few changes. Therefore, as system developers faced with the decision to build an integrated, non-inquisitive or an inquisitive critiquing system, the authors choose the former

Adolescents in clinical remission of atopic asthma have elevated exhaled nitric oxide levels and bronchial hyperresponsiveness

Symptoms of atopic asthma often decrease or even seem to disappear around puberty. The aim of this study was to investigate whether this so-called clinical remission is accompanied by remission of airway inflammation, since symptoms relapse in a substantial proportion of subjects later in life. To assess indicators of inflammation and/or structural damage of the airways, exhaled nitric oxide (eNO) and bronchial responsiveness to adenosine-5'-monophosphate (AMP) and methacholine (MCh) were determined in 21 subjects in clinical remission of atopic asthma. Clinical remission was defined as complete absence of symptoms of asthma without the use of any medication in the year preceding the study. Results were compared with those of 21 patients with current asthma and 18 healthy control subjects. We found significantly higher eNO values in the remission group than in healthy controls (geometric mean, 18.9 and 1.0 ppb, respectively; p < 0.001) whereas eNO values of the remission group and those of the subjects with current asthma (geometric mean, 21.9 ppb) were similar (p = 0.09). The responsiveness to both AMP and MCh of subjects in clinical remission was significantly higher as compared with responsiveness of healthy controls, and lower than responsiveness of subjects with current asthma. A significant correlation could be established between eNO and responsiveness to AMP, but not between eNO and responsiveness to MCh. The results of this study are suggestive of persistent airway inflammation during clinical remission of atopic asthma. We speculate that subclinical inflammation is a risk factor for asthma relapse later in life, and that eNO and responsiveness to both AMP and MCh can be used as different, noninvasive indices of the inflammatory process of the airways

Criticality in confined ionic fluids

A theory of a confined two dimensional electrolyte is presented. The positive and negative ions, interacting by a $1/r$ potential, are constrained to move on an interface separating two solvents with dielectric constants $\epsilon_1$ and $\epsilon_2$. It is shown that the Debye-H\"uckel type of theory predicts that the this 2d Coulomb fluid should undergo a phase separation into a coexisting liquid (high density) and gas (low density) phases. We argue, however, that the formation of polymer-like chains of alternating positive and negative ions can prevent this phase transition from taking place.Comment: RevTex, no figures, in press Phys. Rev.

Children with severe acute asthma admitted to Dutch PICUs: A changing landscape

The number of children requiring pediatric intensive care unit (PICU) admission for severe acute asthma (SAA) around the world has increased. Objectives: We investigated whether this trend in SAA PICU admissions is present in the Netherlands. Methods: A multicenter retrospective cohort study across all tertiary care PICUs in the Netherlands. Inclusion criteria were children (2-18 years) hospitalized for SAA between 2003 and 2013. Data included demographic data, asthma diagnosis, treatment, and mortality. Results: In the 11-year study period 590 children (660 admissions) were admitted to a PICU with a threefold increase in the number of admissions per year over time. The severity of SAA seemed unchanged, based on the first blood gas, length of stay and mortality rate (0.6%). More children received highflow nasal cannula (P<0.001) and fewer children needed invasive ventilation (P<0.001). In 58% of the patients the maximal intravenous (IV) salbutamol infusion rate during PICU admission was 1mcg/kg/min. However, the number of patients treated with IV salbutamol in the referring hospitals increased significantly over time (P=0.005). The proportion of steroid-naïve patients increased from 35% to 54% (P=0.004), with a significant increase in both age groups (2-4 years [P=0.026] and 5-17 years [P=0.036]). Conclusions: The number of children requiring PICU admission for SAA in the Netherlands has increased. We speculate that this threefold increase is explained by an increasing number of steroid-naïve children, in conjunction with a lowered threshold for PICU admission, possibly caused by earlier use of salbutamol IV in the referring hospitals

Dipolar origin of the gas-liquid coexistence of the hard-core 1:1 electrolyte model

We present a systematic study of the effect of the ion pairing on the gas-liquid phase transition of hard-core 1:1 electrolyte models. We study a class of dipolar dimer models that depend on a parameter R_c, the maximum separation between the ions that compose the dimer. This parameter can vary from sigma_{+/-} that corresponds to the tightly tethered dipolar dimer model, to R_c --> infinity, that corresponds to the Stillinger-Lovett description of the free ion system. The coexistence curve and critical point parameters are obtained as a function of R_c by grand canonical Monte Carlo techniques. Our results show that this dependence is smooth but non-monotonic and converges asymptotically towards the free ion case for relatively small values of R_c. This fact allows us to describe the gas-liquid transition in the free ion model as a transition between two dimerized fluid phases. The role of the unpaired ions can be considered as a perturbation of this picture.Comment: 16 pages, 13 figures, submitted to Physical Review

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

The Earth: Plasma Sources, Losses, and Transport Processes

This paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed

Prospective associations of coronary heart disease loci in African Americans using the MetaboChip

Background: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of publishe

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk