Summary Background Stricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohn's disease. Validated models to predict risk ...for complications are not available, and the effect of treatment on risk is unknown. Methods We did a prospective inception cohort study of paediatric patients with newly diagnosed Crohn's disease at 28 sites in the USA and Canada. Genotypes, antimicrobial serologies, ileal gene expression, and ileal, rectal, and faecal microbiota were assessed. A competing-risk model for disease complications was derived and validated in independent groups. Propensity-score matching tested the effect of anti-tumour necrosis factor α (TNFα) therapy exposure within 90 days of diagnosis on complication risk. Findings Between Nov 1, 2008, and June 30, 2012, we enrolled 913 patients, 78 (9%) of whom experienced Crohn's disease complications. The validated competing-risk model included age, race, disease location, and antimicrobial serologies and provided a sensitivity of 66% (95% CI 51–82) and specificity of 63% (55–71), with a negative predictive value of 95% (94–97). Patients who received early anti-TNFα therapy were less likely to have penetrating complications (hazard ratio HR 0·30, 95% CI 0·10–0·89; p=0·0296) but not stricturing complication (1·13, 0·51–2·51; 0·76) than were those who did not receive early anti-TNFα therapy. Ruminococcus was implicated in stricturing complications and Veillonella in penetrating complications. Ileal genes controlling extracellular matrix production were upregulated at diagnosis, and this gene signature was associated with stricturing in the risk model (HR 1·70, 95% CI 1·12–2·57; p=0·0120). When this gene signature was included, the model's specificity improved to 71%. Interpretation Our findings support the usefulness of risk stratification of paediatric patients with Crohn's disease at diagnosis, and selection of anti-TNFα therapy. Funding Crohn's and Colitis Foundation of America, Cincinnati Children's Hospital Research Foundation Digestive Health Center.
ABSTRACT We present the third Fermi Large Area Telescope (LAT) source catalog (3FGL) of sources in the 100 MeV-300 GeV range. Based on the first 4 yr of science data from the Fermi Gamma-ray Space ...Telescope mission, it is the deepest yet in this energy range. Relative to the Second Fermi LAT catalog, the 3FGL catalog incorporates twice as much data, as well as a number of analysis improvements, including improved calibrations at the event reconstruction level, an updated model for Galactic diffuse γ-ray emission, a refined procedure for source detection, and improved methods for associating LAT sources with potential counterparts at other wavelengths. The 3FGL catalog includes 3033 sources above significance, with source location regions, spectral properties, and monthly light curves for each. Of these, 78 are flagged as potentially being due to imperfections in the model for Galactic diffuse emission. Twenty-five sources are modeled explicitly as spatially extended, and overall 238 sources are considered as identified based on angular extent or correlated variability (periodic or otherwise) observed at other wavelengths. For 1010 sources we have not found plausible counterparts at other wavelengths. More than 1100 of the identified or associated sources are active galaxies of the blazar class; several other classes of non-blazar active galaxies are also represented in the 3FGL. Pulsars represent the largest Galactic source class. From source counts of Galactic sources we estimate that the contribution of unresolved sources to the Galactic diffuse emission is ∼3% at 1 GeV.
Hybrid solid-state batteries using a bilayer of ceramic and solid polymer electrolytes may offer advantages over using a single type of solid electrolyte alone. However, the impedance to Li+ ...transport across interfaces between different electrolytes can be high. It is important to determine the resistance to Li+ transport across these heteroionic interfaces, as well as to understand the underlying causes of these resistances; in particular, whether chemical interphase formation contributes to giving high resistances, as in the case of ceramic/liquid electrolyte interfaces. In this work, two ceramic electrolytes, Li3PS4 (LPS) and Li6.5La3Zr1.5Ta0.5O12 (LLZTO), were interfaced with the solid polymer electrolyte PEO10:LiTFSI and the interfacial resistances were determined by impedance spectroscopy. The LLZTO/polymer interfacial resistance was found to be prohibitively high but, in contrast, a low resistance was observed at the LPS/polymer interface that became negligible at a moderately elevated temperature of 50 °C. Chemical characterization of the two interfaces was carried out, using depth-profiled X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry, to determine whether the interfacial resistance was correlated with the formation of an interphase. Interestingly, no interphase was observed at the higher resistance LLZTO/polymer interface, whereas LPS was observed to react with the polymer electrolyte to form an interphase.
While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable ...clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September, 2018 transdisciplinary workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.
The impulsive behavior that is often characteristic of adolescence may reflect underlying neurodevelopmental processes. Moreover, impulsivity is a multi-dimensional construct, and it is plausible ...that distinct brain networks contribute to its different cognitive, clinical and behavioral aspects. As these networks have not yet been described, we identified distinct cortical and subcortical networks underlying successful inhibitions and inhibition failures in a large sample (n = 1,896) of 14-year-old adolescents. Different networks were associated with drug use (n = 1,593) and attention-deficit hyperactivity disorder symptoms (n = 342). Hypofunctioning of a specific orbitofrontal cortical network was associated with likelihood of initiating drug use in early adolescence. Right inferior frontal activity was related to the speed of the inhibition process (n = 826) and use of illegal substances and associated with genetic variation in a norepinephrine transporter gene (n = 819). Our results indicate that both neural endophenotypes and genetic variation give rise to the various manifestations of impulsive behavior.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
7.
Spin rate distribution of small asteroids Pravec, P.; Harris, A.W.; Vokrouhlický, D. ...
Icarus (New York, N.Y. 1962),
10/2008, Letnik:
197, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The spin rate distribution of main belt/Mars crossing (MB/MC) asteroids with diameters 3–15 km is uniform in the range from
f
=
1
to 9.5 d
−1, and there is an excess of slow rotators with
f
<
1
d
−1. ...The observed distribution appears to be controlled by the Yarkovsky–O'Keefe–Radzievskii–Paddack (YORP) effect. The magnitude of the excess of slow rotators is related to the residence time of slowed down asteroids in the excess and the rate of spin rate change outside the excess. We estimated a median YORP spin rate change of
≈
0.022
d
−1
/
Myr
for asteroids in our sample (i.e., a median time in which the spin rate changes by 1 d
−1 is
≈
45
Myr
), thus the residence time of slowed down asteroids in the excess is
≈
110
Myr
. The spin rate distribution of near-Earth asteroids (NEAs) with sizes in the range 0.2–3 km (∼5 times smaller in median diameter than the MB/MC asteroids sample) shows a similar excess of slow rotators, but there is also a concentration of NEAs at fast spin rates with
f
=
9
–
10
d
−1
. The concentration at fast spin rates is correlated with a narrower distribution of spin rates of primaries of binary systems among NEAs; the difference may be due to the apparently more evolved population of binaries among MB/MC asteroids.
Policies of UK clinicians regarding the duration of chemotherapy for patients with advanced colorectal cancer are not consistent. We aimed to compare effectiveness of continuous and intermittent ...chemotherapy in such patients.
Patients who responded or had stable disease after receiving 12 weeks of the regimens described by de Gramont and Lokich, or raltitrexed chemotherapy, were randomised to either intermittent (a break in chemotherapy, re-starting on the same drug on progression), or continuous chemotherapy until progression.
354 patients (178 intermittent, 176 continuous) were enrolled from 42 UK centres. At randomisation, 41% of participants had part or complete response; 59% were stable. Only 66 (37%) patients allocated to intermittent treatment restarted as planned, after a median of 130 days. Median time on treatment after restarting was 84 days. Patients in the continuous group remained on treatment for a median of a further 92 days. Similar proportions of patients in both groups received second-line therapy. Patients on intermittent chemotherapy had significantly fewer toxic effects and serious adverse events than those in the continuous group. There was no clear evidence of a difference in overall survival (hazard ratio 0·87 favouring intermittent, 95% CI 0·69–1·09, p=0·23).
Our findings provided no clear evidence of a benefit in continuing therapy indefinitely until disease progression. They showed that it is safe to stop chemotherapy after 12 weeks and re-start the same treatment on progression in patients with chemosensitive advanced colorectal cancer.
A multiple‐box model was developed to determine how meteorological, anthropogenic, and biological processes combine to produce diel cycles of carbon dioxide (CO2) mole fraction during each of the ...four calendar‐based seasons within Salt Lake Valley, Utah, USA. The model was forced by observed winds, sounding‐derived mixing depths, an anthropogenic CO2 emissions inventory, and net biological flux estimates based on temperature, solar radiation, and ecosystem type. The model was validated using hourly CO2 mole fractions measured at five sites in the urban Salt Lake Valley (uSLV) area for 2005–2009 (spatial average of observations denoted by Cobs). The model accounted for 53% of Cobs on an hourly basis, and accounted for 90–94% of the mean diel cycle of Cobs depending on season. The multiple‐box model results indicated that CO2 change rates within the uSLV mean diel cycles were largely the result of imbalances between anthropogenic processes adding CO2 and meteorological processes removing or diluting CO2. Removal by wind (advection) was the most important CO2 reduction process on average, but dilution of CO2 by entrainment of air from above the mixing height overtook advection in importance between sunrise and midday. During summer mornings, CO2 reduction attributable to photosynthesis below shallow mixing heights was of intermediate importance between advection and entrainment, but the overall net effect of biological processes was the least important influence on CO2 change rates during each of the four seasons.
Key Points
Multiple‐box model explains observed diel cycles of urban Salt Lake Valley CO2
Cycles are imbalance between anthropogenic and meteorological processes
Bioglogical processes are of tertiary importance year‐round
Photometric data on 17 binary near-Earth asteroids (15 of them are certain detections, two are probables) were analysed and characteristic properties of the near-Earth asteroid (NEA) binary ...population were inferred. We have found that binary systems with a secondary-to-primary mean diameter ratio
D
s
/
D
p
⩾
0.18
concentrate among NEAs smaller than 2 km in diameter; the abundance of such binaries decreases significantly among larger NEAs. Secondaries show an upper size limit of
D
s
=
0.5
–
1
km
. Systems with
D
s
/
D
p
⩽
0.5
are abundant but larger satellites are significantly less common. Primaries have spheroidal shapes and they rotate rapidly, with periods concentrating between 2.2 to 2.8 h and with a tail of the distribution up to ∼4 h. The fast rotators are close to the critical spin for rubble piles with bulk densities about 2 g/cm
3. Orbital periods show an apparent cut-off at
P
orb
∼
11
h
; closer systems with shorter orbital periods have not been discovered, which is consistent with the Roche limit for strengthless bodies. Secondaries are more elongated on average than primaries. Most, but not all, of their rotations appear to be synchronized with the orbital motion; nonsynchronous secondary rotations may occur especially among wider systems with
P
orb
>
20
h. The specific total angular momentum of most of the binary systems is similar to within ±20% and close to the angular momentum of a sphere with the same total mass and density, rotating at the disruption limit; this suggests that the binaries were created by mechanism(s) related to rotation near the critical limit and that they neither gained nor lost significant amounts of angular momentum during or since formation. A comparison with six small asynchronous binaries detected in the main belt of asteroids suggests that the population extends beyond the region of terrestrial planets, but with characteristics shifted to larger sizes and longer periods. The estimated mean proportion of binaries with
D
s
/
D
p
⩾
0.18
among NEAs larger than 0.3 km is
15
±
4
%
. Among fastest rotating NEAs larger than 0.3 km with periods between 2.2 and 2.8 h, the mean proportion of such binaries is (66
+10
−12)%.
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