Vitamin D is an important micronutrient for health. Hypovitaminosis D is thought to play a role in the seasonality of a number of diseases and adverse health conditions. To refine hypotheses about ...the links between vitamin D and seasonal diseases, good estimates of the cyclicality of serum vitamin D are necessary.
The objective of this study is to describe quantitatively the cyclicality of 25-hydroxyvitamin D (25OHD) in the United States. We provide a statistical analysis with weekly time resolution, in comparison to the quarterly (winter/spring/summer/fall) estimates already in the literature.
We analyzed time series data on 25OHD, spanning 287 consecutive weeks. The pooled data set comes from 3.44 million serum samples from the United States. We statistically analyzed the proportion of sera that were vitamin D sufficient, defined as 25OHD Formula: see text ng/mL, as a function of date.
In the United States, serum 25OHD follows a lagged pattern relative to the astronomical seasons, peaking in late summer (August) and troughing in late winter (February). Airmass, which is a function of solar altitude, fits the 25OHD data very well when lagged by 8 weeks.
Serum vitamin D levels can be modeled as a function of date, working through a double-log transformation of minimal solar airmass (easily calculated from solar altitude, retrievable from an online solar altitude/azimuth table).
The Gutenberg-Richter frequency-magnitude distribution of earthquakes has become well established in seismology. The slope of the relation between frequency and magnitude (b value) is typically 1, ...but it often shows variations around 1. Based on an analysis of seismicity prior to the 2011 Tohoku and 2004 Sumatra earthquakes (both in magnitude (M) 9 class), we show that the pronounced decade-scale decrease in b value was a common precursor to both mega-quakes around their hypocenters. This is the first report on M9-class quakes to confirm a change in b value, which has been predicted based on the results of laboratory experiments. We propose that the b value is an important indicator of an impending great earthquake, and has great potential in terms of predicting a future large quake off the Pacific coast of Hokkaido, Japan.
The Large Hadron Collider forward (LHCf) experiment is designed to use the LHC to verify the hadronic-interaction models used in cosmic-ray physics. Forward baryon production is one of the crucial ...points to understand the development of cosmic-ray showers. We report the neutron-energy spectra for LHC s=7 TeV proton–proton collisions with the pseudo-rapidity η ranging from 8.81 to 8.99, from 8.99 to 9.22, and from 10.76 to infinity. The measured energy spectra obtained from the two independent calorimeters of Arm1 and Arm2 show the same characteristic feature before unfolding the detector responses. We unfolded the measured spectra by using the multidimensional unfolding method based on Bayesian theory, and the unfolded spectra were compared with current hadronic-interaction models. The QGSJET II-03 model predicts a high neutron production rate at the highest pseudo-rapidity range similar to our results, and the DPMJET 3.04 model describes our results well at the lower pseudo-rapidity ranges. However, no model perfectly explains the experimental results over the entire pseudo-rapidity range. The experimental data indicate a more abundant neutron production rate relative to the photon production than any model predictions studied here.
The aim of this study was to evaluate the usefulness of EGFR mutation status in serum DNA as a means of predicting a benefit from gefitinib (IRESSA) therapy in Japanese patients with non-small cell ...lung cancer (NSCLC). We obtained pairs of tumour and serum samples from 42 patients treated with gefitinib. EGFR mutation status was determined by a direct sequencing method and by Scorpion Amplification Refractory Mutation System (ARMS) technology. EGFR mutations were detected in the tumour samples of eight patients and in the serum samples of seven patients. EGFR mutation status in the tumours and serum samples was consistent in 39 (92.9%) of the 42 pairs. EGFR mutations were strong correlations between both EGFR mutation status in the tumour samples and serum samples and objective response to gefitinib (P<0.001). Median progression-free survival time was significantly longer in the patients with EGFR mutations than in the patients without EGFR mutations (194 vs 55 days, P=0.016, in tumour samples; 174 vs 58 days, P=0.044, in serum samples). The results suggest that it is feasible to use serum DNA to detect EGFR mutation, and that it's potential as a predictor of response to, and survival on gefitinib is worthy of further evaluation.
We evaluated whether tissue tumor mutational burden (tTMB) and STK11, KEAP1, and KRAS mutations have clinical utility as biomarkers for pembrolizumab monotherapy versus platinum-based chemotherapy in ...patients with programmed death ligand 1 (PD-L1)-positive (tumor proportion score ≥1%) advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations in the phase III KEYNOTE-042 trial.
This retrospective exploratory analysis assessed prevalence of tTMB and STK11, KEAP1, and KRAS mutations determined by whole-exome sequencing of tumor tissue and matched normal DNA and their associations with outcomes in KEYNOTE-042. Clinical utility of tTMB was assessed using a prespecified cut point of 175 mutations/exome.
Of 793 patients, 345 (43.5%) had tTMB ≥175 mutations/exome and 448 (56.5%) had tTMB <175 mutations/exome. No association was observed between PD-L1 expression and tTMB. Continuous tTMB score was associated with improved overall survival (OS) and progression-free survival among patients receiving pembrolizumab (Wald test, one-sided P < 0.001) but not those receiving chemotherapy (Wald test, two-sided P > 0.05). tTMB ≥175 mutations/exome was associated with improved outcomes for pembrolizumab versus chemotherapy, whereas tTMB <175 mutations/exome was not {OS: hazard ratio, 0.62 95% confidence interval (CI) 0.48-0.80 and 1.09 (95% CI 0.88-1.36); progression-free survival: 0.75 (0.59-0.95) and 1.27 (1.04-1.55), respectively}. Improved OS hazard ratio (95% CI) for pembrolizumab versus chemotherapy was observed regardless of STK11 STK11 mutant (n = 33): 0.37 (0.16-0.86), STK11 wild-type (n = 396): 0.83 (0.65-1.05); KEAP1 KEAP1 mutant (n = 64): 0.75 (0.42-1.35), KEAP1 wild-type (n = 365): 0.78 (0.61-0.99), or KRAS KRAS mutant (n = 69): 0.42 (0.22-0.81); KRAS wild-type (n = 232): 0.86 (0.63-1.18) mutation status.
tTMB with a cut point of ≥175 mutations/exome is a potential predictive biomarker for pembrolizumab monotherapy for advanced/metastatic PD-L1 tumor proportion score ≥1% NSCLC. Pembrolizumab is a standard first-line treatment in this setting regardless of STK11, KEAP1, or KRAS mutation status.
•Pembrolizumab monotherapy is a standard first-line treatment of patients with PD-L1-positive advanced/metastatic NSCLC.•We assessed clinical utility of potential biomarkers among patients receiving pembrolizumab versus chemotherapy.•tTMB ≥175 mutations/exome was associated with improved outcomes among patients receiving pembrolizumab versus chemotherapy.•tTMB has potential clinical utility as a biomarker for pembrolizumab in first-line PD-L1-positive advanced/metastatic NSCLC.•Pembrolizumab improved overall survival versus chemotherapy regardless of STK11, KEAP1, or KRAS mutation status.
A
bstract
In this paper, we report the measurement of the energy flow, the cross section and the average inelasticity of forward neutrons (+ antineutrons) produced in
s
= 13 TeV proton-proton ...collisions. These quantities are obtained from the inclusive differential production cross section, measured using the LHCf Arm2 detector at the CERN Large Hadron Collider. The measurements are performed in six pseudorapidity regions: three of them (
η >
10
.
75, 8
.
99
< η <
9
.
21 and 8
.
80
< η <
8
.
99), albeit with smaller acceptance and larger uncertainties, were already published in a previous work, whereas the remaining three (10
.
06
< η <
10
.
75, 9
.
65
< η <
10
.
06 and 8
.
65
< η <
8
.
80) are presented here for the first time. The analysis was carried out using a data set acquired in June 2015 with a corresponding integrated luminosity of 0
.
194 nb
−
1
. Comparing the experimental measurements with the expectations of several hadronic interaction models used to simulate cosmic ray air showers, none of these generators resulted to have a satisfactory agreement in all the phase space selected for the analysis. The inclusive differential production cross section for
η >
10
.
75 is not reproduced by any model, whereas the results still indicate a significant but less serious deviation at lower pseudorapidities. Depending on the pseudorapidity region, the generators showing the best overall agreement with data are either SIBYLL 2.3 or EPOS-LHC. Furthermore, apart from the most forward region, the derived energy flow and cross section distributions are best reproduced by EPOS-LHC. Finally, even if none of the models describe the elasticity distribution in a satisfactory way, the extracted average inelasticity is consistent with the QGSJET II-04 value, while most of the other generators give values that lie just outside the experimental uncertainties.
A
bstract
In this paper, we report the measurement relative to the production of forward neutrons in proton-proton collisions at
s
=
13
TeV obtained using the LHCf Arm2 detector at the Large Hadron ...Collider. The results for the inclusive differential production cross section are presented as a function of energy in three different pseudorapidity regions:
η
> 10.76, 8.99 <
η
< 9.22 and 8.81 <
η
< 8.99. The analysis was performed using a data set acquired in June 2015 that corresponds to an integrated luminosity of 0.194 nb
−1
. The measurements were compared with the predictions of several hadronic interaction models used to simulate air showers generated by Ultra High Energy Cosmic Rays. None of these generators showed good agreement with the data for all pseudorapidity intervals. For
η
> 10.76, no model is able to reproduce the observed peak structure at around 5 TeV and all models underestimate the total production cross section: among them, QGSJET II-04 shows the smallest deficit with respect to data for the whole energy range. For 8.99 <
η
< 9.22 and 8.81 <
η
< 8.99, the models having the best overall agreement with data are SIBYLL 2.3 and EPOS-LHC, respectively: in particular, in both regions SIBYLL 2.3 is able to reproduce the observed peak structure at around 1.5–2.5 TeV.
PDF
