Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural ...damage to the bowel, which may predict long‐term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lémann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be “diagnostic modality driven”: for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross‐sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lémann score is expected to be able to portray a patient's disease course on a double‐axis graph, with time as the x‐axis, bowel damage severity as the y‐axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage. (Inflamm Bowel Dis 2011)
In this paper we present an in-depth study of the distributions of various neutral species in Titan's upper atmosphere, between 950 and 1500 km for abundant species (N
2, CH
4, H
2) and between 950 ...and 1200 km for other minor species. Our analysis is based on a large sample of Cassini/INMS (Ion Neutral Mass Spectrometer) measurements in the CSN (Closed Source Neutral) mode, obtained during 15 close flybys of Titan. To untangle the overlapping cracking patterns, we adopt Singular Value Decomposition (SVD) to determine simultaneously the densities of different species. Except for N
2, CH
4, H
2 and
40Ar (as well as their isotopes), all species present density enhancements measured during the outbound legs. This can be interpreted as a result of wall effects, which could be either adsorption/desorption of these molecules or heterogeneous surface chemistry of the associated radicals on the chamber walls. In this paper, we provide both direct inbound measurements assuming ram pressure enhancement only and abundances corrected for wall adsorption/desorption based on a simple model to reproduce the observed time behavior. Among all minor species of photochemical interest, we have firm detections of C
2H
2, C
2H
4, C
2H
6, CH
3C
2H, C
4H
2, C
6H
6, CH
3CN, HC
3N, C
2N
2 and NH
3 in Titan's upper atmosphere. Upper limits are given for other minor species.
The globally averaged distributions of N
2, CH
4 and H
2 are each modeled with the diffusion approximation. The N
2 profile suggests an average thermospheric temperature of 151 K. The CH
4 and H
2 profiles constrain their fluxes to be
2.6
×
10
9
cm
−
2
s
−
1
and
1.1
×
10
10
cm
−
2
s
−
1
, referred to Titan's surface. Both fluxes are significantly higher than the Jeans escape values. The INMS data also suggest horizontal/diurnal variations of temperature and neutral gas distribution in Titan's thermosphere. The equatorial region, the ramside, as well as the nightside hemisphere of Titan appear to be warmer and present some evidence for the depletion of light species such as CH
4. Meridional variations of some heavy species are also observed, with a trend of depletion toward the north pole. Though some of the above variations might be interpreted by either the solar-driven models or auroral-driven models, a physical scenario that reconciles all the observed horizontal/diurnal variations in a consistent way is still missing. With a careful evaluation of the effect of restricted sampling, some of the features shown in the INMS data are more likely to be observational biases.
‘Cell-based’ models provide a powerful computational tool for studying the mechanisms underlying the growth and dynamics of biological tissues in health and disease. An increasing amount of ...quantitative data with cellular resolution has paved the way for the quantitative parameterisation and validation of such models. However, the numerical implementation of cell-based models remains challenging, and little work has been done to understand to what extent implementation choices may influence model predictions. Here, we consider the numerical implementation of a popular class of cell-based models called vertex models, which are often used to study epithelial tissues. In two-dimensional vertex models, a tissue is approximated as a tessellation of polygons and the vertices of these polygons move due to mechanical forces originating from the cells. Such models have been used extensively to study the mechanical regulation of tissue topology in the literature. Here, we analyse how the model predictions may be affected by numerical parameters, such as the size of the time step, and non-physical model parameters, such as length thresholds for cell rearrangement. We find that vertex positions and summary statistics are sensitive to several of these implementation parameters. For example, the predicted tissue size decreases with decreasing cell cycle durations, and cell rearrangement may be suppressed by large time steps. These findings are counter-intuitive and illustrate that model predictions need to be thoroughly analysed and implementation details carefully considered when applying cell-based computational models in a quantitative setting.
Climate sensitivity in Earth system models (ESMs) is an emergent
property that is affected by structural (missing or inaccurate model physics)
and parametric (variations in model parameters) ...uncertainty. This work
provides the first quantitative assessment of the role of compensation
between uncertainties in aerosol forcing and atmospheric parameters, and
their impact on the climate sensitivity of the Community Atmosphere Model,
Version 4 (CAM4). Running the model with prescribed ocean and ice conditions,
we perturb four parameters related to sulfate and black carbon aerosol
radiative forcing and distribution, as well as five atmospheric parameters
related to clouds, convection, and radiative flux. In this experimental setup
where aerosols do not affect the properties of clouds, the atmospheric
parameters explain the majority of variance in climate sensitivity, with two
parameters being the most important: one controlling low cloud amount, and
one controlling the timescale for deep convection. Although the aerosol
parameters strongly affect aerosol optical depth, their impacts on climate
sensitivity are substantially weaker than the impacts of the atmospheric
parameters, but this result may depend on whether aerosol–cloud interactions
are simulated. Based on comparisons to inter-model spread of other ESMs, we
conclude that structural uncertainties in this configuration of CAM4 likely
contribute 3 times more to uncertainty in climate sensitivity than
parametric uncertainties. We provide several parameter sets that could
provide plausible (measured by a skill score) configurations of CAM4, but
with different sulfate aerosol radiative forcing, black carbon radiative
forcing, and climate sensitivity.
Effectively modeling the influence of terrestrial snow on climate in general circulation models is limited by imperfect knowledge and parameterization of arctic and subarctic climate processes and a ...lack of reliable observations for model evaluation and improvement. This study uses a number of satellite‐derived data sets to evaluate how well the current generation of climate models from the Fifth Coupled Model Intercomparison Project (CMIP5) simulate the seasonal cycle of climatological snow cover fraction (SCF) and surface albedo over the Northern Hemisphere snow season (September–June). Using a variety of metrics, the CMIP5 models are found to simulate SCF evolution better than that of albedo. The seasonal cycle of SCF is well reproduced despite substantial biases in simulated surface albedo of snow‐covered land (αsfc_snow), which affect both the magnitude and timing of the seasonal peak in αsfc_snow during the fall snow accumulation period, and the springtime snow ablation period. Insolation weighting demonstrates that the biases in αsfc_snow during spring are of greater importance for the surface energy budget. Albedo biases are largest across the boreal forest, where the simulated seasonal cycle of albedo is biased high in 15/16 CMIP5 models. This bias is explained primarily by unrealistic treatment of vegetation masking and subsequent overestimation (more than 50% in some cases) of peak αsfc_snow rather than by biases in SCF. While seemingly straightforward corrections to peak αsfc_snow could yield significant improvements to simulated snow albedo feedback, changes in αsfc_snow could potentially introduce biases in other important model variables such as surface temperature.
Key Points
Models better simulate the monthly change in SCF than the change in albedo
Albedo biases are related to the magnitude and timing of peak snow albedo
Model performance is weakest over the boreal forest and during the melt period
Contrary to conventional wisdom, the rectoanal gradient during evacuation is negative in many healthy people, undermining the utility of anorectal high-resolution manometry (HRM) for diagnosing ...defecatory disorders. We aimed to compare HRM and magnetic resonance imaging (MRI) for assessing rectal evacuation and structural abnormalities.
We performed a retrospective analysis of 118 patients (all female; 51 with constipation, 48 with fecal incontinence, and 19 with rectal prolapse; age, 53 ± 1 years) assessed by HRM, the rectal balloon expulsion test (BET), and MRI at Mayo Clinic, Rochester, Minnesota, from February 2011 through March 2013. Thirty healthy asymptomatic women (age, 37 ± 2 years) served as controls. We used principal components analysis of HRM variables to identify rectoanal pressure patterns associated with rectal prolapse and phenotypes of patients with prolapse.
Compared with patients with normal findings from the rectal BET, patients with an abnormal BET had lower median rectal pressure (36 vs 22 mm Hg, P = .002), a more negative median rectoanal gradient (-6 vs -29 mm Hg, P = .006) during evacuation, and a lower proportion of evacuation on the basis of MRI analysis (median of 40% vs 80%, P < .0001). A score derived from rectal pressure and anorectal descent during evacuation and a patulous anal canal was associated (P = .005) with large rectoceles (3 cm or larger). A principal component (PC) logistic model discriminated between patients with and without prolapse with 96% accuracy. Among patients with prolapse, there were 2 phenotypes, which were characterized by high (PC1) or low (PC2) anal pressures at rest and squeeze along with higher rectal and anal pressures (PC1) or a higher rectoanal gradient during evacuation (PC2).
In a retrospective analysis of patients assessed by HRM, measurements of rectal evacuation by anorectal HRM, BET, and MRI were correlated. HRM alone and together with anorectal descent during evacuation may identify rectal prolapse and large rectoceles, respectively, and also identify unique phenotypes of rectal prolapse.
The food-borne pathogen Vibrio parahaemolyticus has been reported as being present in New Zealand (NZ) seawaters, but there have been no reported outbreaks of food-borne infection from commercially ...grown NZ seafood. Our study determined the current incidence of V. parahaemolyticus in NZ oysters and Greenshell mussels and the prevalence of V. parahaemolyticus tdh and trh strains. Pacific (235) and dredge (21) oyster samples and mussel samples (55) were obtained from commercial shellfish-growing areas between December 2009 and June 2012. Total V. parahaemolyticus numbers and the presence of pathogenic genes tdh and trh were determined using the FDA most-probable-number (MPN) method and confirmed using PCR analysis. In samples from the North Island of NZ, V. parahaemolyticus was detected in 81% of Pacific oysters and 34% of mussel samples, while the numbers of V. parahaemolyticus tdh and trh strains were low, with just 3/215 Pacific oyster samples carrying the tdh gene. V. parahaemolyticus organisms carrying tdh and trh were not detected in South Island samples, and V. parahaemolyticus was detected in just 1/21 dredge oyster and 2/16 mussel samples. Numbers of V. parahaemolyticus organisms increased when seawater temperatures were high, the season when most commercial shellfish-growing areas are not harvested. The numbers of V. parahaemolyticus organisms in samples exceeded 1,000 MPN/g only when the seawater temperatures exceeded 19°C, so this environmental parameter could be used as a trigger warning of potential hazard. There is some evidence that the total V. parahaemolyticus numbers increased compared with those reported from a previous 1981 to 1984 study, but the analytical methods differed significantly.
Projections of twenty-first-century Northern Hemisphere (NH) spring snow cover extent (SCE) from two climate model ensembles are analyzed to characterize their uncertainty. Phase 5 of the Coupled ...Model Intercomparison Project (CMIP5) multimodel ensemble exhibits variability resulting from both model differences and internal climate variability, whereas spread generated from a Canadian Earth System Model–Large Ensemble (CanESM-LE) experiment is solely a result of internal variability. The analysis shows that simulated 1981–2010 spring SCE trends are slightly weaker than observed (using an ensemble of snow products). Spring SCE is projected to decrease by −3.7% ± 1.1% decade−1 within the CMIP5 ensemble over the twenty-first century. SCE loss is projected to accelerate for all spring months over the twenty-first century, with the exception of June (because most snow in this month has melted by the latter half of the twenty-first century). For 30-yr spring SCE trends over the twenty-first century, internal variability estimated from CanESM-LE is substantial, but smaller than intermodel spread from CMIP5. Additionally, internal variability in NH extratropical land warming trends can affect SCE trends in the near future (R² = 0.45), while variability in winter precipitation can also have a significant (but lesser) impact on SCE trends. On the other hand, a majority of the intermodel spread is driven by differences in simulated warming (dominant in March–May) and snow cover available for melt (dominant in June). The strong temperature–SCE linkage suggests that model uncertainty in projections of SCE could be potentially reduced through improved simulation of spring season warming over land.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Embryogenesis is an extraordinarily robust process, exhibiting the ability to control tissue size and repair patterning defects in the face of environmental and genetic perturbations. The size and ...shape of a developing tissue is a function of the number and size of its constituent cells as well as their geometric packing. How these cellular properties are coordinated at the tissue level to ensure developmental robustness remains a mystery; understanding this process requires studying multiple concurrent processes that make up morphogenesis, including the spatial patterning of cell fates and apoptosis, as well as cell intercalations. In this work, we develop a computational model that aims to understand aspects of the robust pattern repair mechanisms of the Drosophila embryonic epidermal tissues. Size control in this system has previously been shown to rely on the regulation of apoptosis rather than proliferation; however, to date little work has been done to understand the role of cellular mechanics in this process. We employ a vertex model of an embryonic segment to test hypotheses about the emergence of this size control. Comparing the model to previously published data across wild type and genetic perturbations, we show that passive mechanical forces suffice to explain the observed size control in the posterior (P) compartment of a segment. However, observed asymmetries in cell death frequencies across the segment are demonstrated to require patterning of cellular properties in the model. Finally, we show that distinct forms of mechanical regulation in the model may be distinguished by differences in cell shapes in the P compartment, as quantified through experimentally accessible summary statistics, as well as by the tissue recoil after laser ablation experiments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to evaluate the clinical impact of a higher spatial resolution, full field-of-view investigational photon-counting detector computed tomography (PCD-CT) on radiologist ...confidence in imaging findings and diagnosis of usual interstitial pneumonia (UIP) compared with conventional energy-integrating detector CT (EID-CT).
Patients suspected of interstitial lung disease were scanned on a PCD-CT system after informed consent and a clinically indicated EID-CT. In 2 sessions, 3 thoracic radiologists blinded to clinical history and scanner type evaluated CT images of the right and left lungs separately on EID- or PCD-CT, reviewing each lung once/session, rating confidence in imaging findings of reticulation, traction bronchiectasis, honeycombing, ground-glass opacities (GGOs), mosaic pattern, and lower lobe predominance (100-point scale: 0-33, likely absent; 34-66, indeterminate; 67-100, likely present). Radiologists also rated confidence for the probability of UIP (0-20, normal; 21-40, inconsistent with UIP; 41-60, indeterminate UIP; 61-81; probable UIP; 81-100, definite UIP) and graded image quality. Because a confidence scale of 50 represented completely equivocal findings, magnitude score (the absolute value of confidence scores from 50) was used for analysis (higher scores were more confident). Image noise was measured for each modality. The magnitude score was compared using linear mixed effects regression. The consistency of findings and diagnosis between 2 scanners were evaluated using McNemar test and weighted κ statistics, respectively.
A total of 30 patients (mean age, 68.8 ± 11.0 years; M:F = 18:12) underwent conventional EID-CT (median CTDIvol, 7.88 mGy) and research PCD-CT (median CTDIvol, 6.49 mGy). The magnitude scores in PCD-CT were significantly higher than EID-CT for imaging findings of reticulation (40.7 vs 38.3; P = 0.023), GGO (34.4 vs 31.7; P = 0.019), and mosaic pattern (38.6 vs 35.9; P = 0.013), but not for other imaging findings (P ≥ 0.130) or confidence in UIP (34.1 vs 22.2; P < 0.059). Magnitude score of probability of UIP in PCD-CT was significantly higher than EID-CT in one reader (26.0 vs 21.5; P = 0.009). Photon-counting detector CT demonstrated a decreased number of indeterminate GGO (17 vs 26), an increased number of unlikely GGO (74 vs 50), and an increased number of likely reticulations (140 vs 130) relative to EID-CT. Interobserver agreements among 3 readers for imaging findings and probability of UIP were similar between PCD-CT and EID-CT (intraclass coefficient: 0.507-0.818 vs 0.601-0.848). Photon-counting detector CT had higher scores in overall image quality (4.84 ± 0.38) than those in EID-CT (4.02 ± 0.40; P < 0.001) despite increased image noise (mean 85.5 vs 36.1 HU).
Photon-counting detector CT provided better image quality and improved the reader confidence for presence or absence of imaging findings of reticulation, GGO, and mosaic pattern with idiosyncratic improvement in confidence in UIP presence.
PDF
