This manuscript describes our experience in early identifying MDR-TB cases in high-risk populations by setting up a single-referral molecular diagnosis laboratory in Taiwan. Taiwan Centers for ...Disease Control designated a single-referral laboratory to provide the GenoType MTBDR
plus
test for screening high-risk MDR-TB populations nationwide in 2012–2015. A total of 5,838 sputum specimens from 3,308 patients were tested within 3 days turnaround time. Compared with the conventional culture and drug susceptibility testing, the overall performance of the GenoType MTBDR
plus
test for detecting TB infection showed accuracy of 70.7%, sensitivity of 85.9%, specificity of 65.7%, positive predictive value of 45.5%, and negative predictive value of 93.3%. And the accuracy of detecting rifampin (RIF) resistance, isoniazid (INH) resistance, and MDR-TB (resistant to at least RIF and INH) were 96.5%, 95.2%, and 97.7%, respectively. MDR-TB contacts presented a higher rate of mutated codons 513–519, GenoType MTBDR
plus
banding pattern:
rpoB
WT3(−), and
rpoB
WT4(−) than the treatment failure group. The MDR-TB contact group also had a higher rate of
inhA
C15T mutation, banding pattern:
inh
A WT1(−), and
inhA
MUT1(+) than the recurrent group. Resistance profiles of MDR-TB isolates also varied geographically. The referral molecular diagnosis system contributed to rapid detection and initiation of appropriate therapy.
A
bstract
The Sp(4) gauge theory with two Dirac fundamental flavours provides a candidate for the microscopic origin of composite-Higgs models based on the SU(4)/Sp(4) coset. We employ a combination ...of two different, complementary strategies for the numerical lattice calculations, based on the Hybrid Monte Carlo and on the Heat Bath algorithms. We perform pure Yang-Mills, quenched computations and exploratory studies with dynamical Wilson fermions.
We present the first results in the literature for the spectrum of glueballs of the pure Sp(4) Yang-Mills theory, an EFT framework for the interpretation of the masses and decay constants of the lightest pion, vector and axial-vector mesons, and a preliminary calculation of the latter in the quenched approximation. We show the first numerical evidence of a bulk phase transition in the lattice theory with dynamical Wilson fermions, and perform the technical steps necessary to set up future investigations of the mesonic spectrum of the full theory.
Uncertainty in equilibrium climate sensitivity impedes accurate climate projections. While the intermodel spread is known to arise primarily from differences in cloud feedback, the exact processes ...responsible for the spread remain unclear. To help identify some key sources of uncertainty, the authors use a developmental version of the next-generation Geophysical Fluid Dynamics Laboratory global climate model (GCM) to construct a tightly controlled set of GCMs where only the formulation of convective precipitation is changed. The different models provide simulation of present-day climatology of comparable quality compared to the model ensemble from phase 5 of CMIP (CMIP5). The authors demonstrate that model estimates of climate sensitivity can be strongly affected by the manner through which cumulus cloud condensate is converted into precipitation in a model’s convection parameterization, processes that are only crudely accounted for in GCMs. In particular, two commonly used methods for converting cumulus condensate into precipitation can lead to drastically different climate sensitivity, as estimated here with an atmosphere–land model by increasing sea surface temperatures uniformly and examining the response in the top-of-atmosphere energy balance. The effect can be quantified through a bulk convective detrainment efficiency, which measures the ability of cumulus convection to generate condensate per unit precipitation. The model differences, dominated by shortwave feedbacks, come from broad regimes ranging from large-scale ascent to subsidence regions. Given current uncertainties in representing convective precipitation microphysics and the current inability to find a clear observational constraint that favors one version of the authors’ model over the others, the implications of this ability to engineer climate sensitivity need to be considered when estimating the uncertainty in climate projections.
Summary
Background
The burden of gastroesophageal reflux disease (GERD) is increasing in the Asia area and the majority of GERD patients have non‐erosive reflux disease (NERD).
Aim
To evaluate the ...efficacy and safety of sodium alginate suspension compared to omeprazole in adult subjects with NERD.
Methods
In this 4‐week, double‐blind, parallel study, 195 NERD subjects were randomised to one of two treatment groups: sodium alginate suspension 20 mL three times a day and omeprazole 20 mg once daily. The primary efficacy endpoint was the percentage of patients achieving adequate heartburn or regurgitation relief at day 28 assessed by patient diary. The secondary efficacy endpoints included percentage of patients achieving adequate heartburn or regurgitation relief, change from baseline of the Reflux Disease Questionnaire total score at day 14 and 28 from baseline, and patients’ overall satisfaction.
Results
In this study, 183 subjects were included in the intent‐to‐treat population, and 172 subjects were included in the per‐protocol population. Non‐inferiority of sodium alginate to omeprazole was demonstrated in the intent‐to‐treat population difference, 2.7% (53.3% vs. 50.5%, P = 0.175), 95% lower confidence interval −11.9%, above the preset margin of −19%. All of the secondary efficacy endpoints were comparable between two groups. The incidence of adverse event was relatively low and there was no difference between the two groups (5.4% vs. 5.5% for sodium alginate vs. omeprazole). No severe adverse event was noted in this study.
Conclusion
The study showed that sodium alginate was as effective as omeprazole for symptomatic relief in patients with non‐erosive reflux disease (Clinicaltrials.gov NCT01338077).
The degree and the origins of quantitative variability of most human plasma proteins are largely unknown. Because the twin study design provides a natural opportunity to estimate the relative ...contribution of heritability and environment to different traits in human population, we applied here the highly accurate and reproducible SWATH mass spectrometry technique to quantify 1,904 peptides defining 342 unique plasma proteins in 232 plasma samples collected longitudinally from pairs of monozygotic and dizygotic twins at intervals of 2–7 years, and proportioned the observed total quantitative variability to its root causes, genes, and environmental and longitudinal factors. The data indicate that different proteins show vastly different patterns of abundance variability among humans and that genetic control and longitudinal variation affect protein levels and biological processes to different degrees. The data further strongly suggest that the plasma concentrations of clinical biomarkers need to be calibrated against genetic and temporal factors. Moreover, we identified 13 cis‐SNPs significantly influencing the level of specific plasma proteins. These results therefore have immediate implications for the effective design of blood‐based biomarker studies.
Synopsis
The degree and origins of the abundance variability of 342 human plasma proteins are analyzed by a longitudinal twin design and SWATH mass spectrometry. The results suggest genetic control and longitudinal variation affect protein levels and biological processes to different degrees.
We used the highly accurate and reproducible SWATH mass spectrometry technique to quantify 342 unique plasma proteins in 232 plasma samples collected longitudinally from pairs of monozygotic and dizygotic twins at intervals of 2–7 years.
The observed total quantitative variability of human plasma proteome is dissected to its root causes, genes, environment and longitudinal factors.
The roles of the heritable, environmental and longitudinal determinants in controlling plasma protein levels are different for different proteins and functional clusters, strongly suggesting that the plasma concentrations of clinical biomarkers need to be calibrated against genetic and temporal factors.
We further identified 13 cis‐SNPs significantly influencing the level of specific plasma proteins as protein quantitative trait loci (pQTLs), and five of them are associated with gene expression QTLs (eQTLs) in human tissues.
The degree and origins of the abundance variability of 342 human plasma proteins are analyzed by a longitudinal twin design and SWATH mass spectrometry. The results suggest genetic control and longitudinal variation affect protein levels and biological processes to different degrees.
To evaluate the possible association between paediatric head computed tomography (CT) examination and increased subsequent risk of malignancy and benign brain tumour.
In the exposed cohort, 24 418 ...participants under 18 years of age, who underwent head CT examination between 1998 and 2006, were identified from the Taiwan National Health Insurance Research Database (NHIRD). Patients were followed up until a diagnosis of malignant disease or benign brain tumour, withdrawal from the National Health Insurance (NHI) system, or at the end of 2008.
The overall risk was not significantly different in the two cohorts (incidence rate=36.72 per 100 000 person-years in the exposed cohort, 28.48 per 100 000 person-years in the unexposed cohort, hazard ratio (HR)=1.29, 95% confidence interval (CI)=0.90-1.85). The risk of benign brain tumour was significantly higher in the exposed cohort than in the unexposed cohort (HR=2.97, 95% CI=1.49-5.93). The frequency of CT examination showed strong correlation with the subsequent overall risk of malignancy and benign brain tumour.
We found that paediatric head CT examination was associated with an increased incidence of benign brain tumour. A large-scale study with longer follow-up is necessary to confirm this result.
A box model for estimating bidirectional air–surface exchange of gaseous elemental mercury (Hg0) has been updated based on the latest understanding of the resistance scheme of atmosphere–biosphere ...interface transfer. Simulations were performed for two seasonal months to evaluate diurnal and seasonal variation. The base-case results show that water and soil surfaces are net sources, while vegetation is a net sink of Hg0. The estimated net exchange in a domain covering the contiguous US and part of Canada and Mexico is 38.4 and 56.0 Mg as evasion in the summer and winter month, respectively. The smaller evasion in summer is due to the stronger Hg0 uptake by vegetation. Modeling experiments using a two-level factorial design were conducted to examine the sensitivity of flux response to the changes in physical and environmental parameters in the model. It is shown that atmospheric shear flows (surface wind over water and friction velocity over terrestrial surfaces), dissolved gaseous mercury (DGM) concentration, soil organic and Hg content, and air temperature are the most influential factors. The positive effect of friction velocity and soil Hg content on the evasion flux from soil and canopy can be effectively offset by the negative effect of soil organic content. Significant synergistic effects are identified between surface wind and DGM level for water surface, and between soil Hg content and friction velocity for soil surface, leading to ~50% enhanced flux compared to the sum of their individual effects. The air–foliage exchange is mainly controlled by surface resistance terms influenced by solar irradiation and air temperature. Research in providing geospatial distribution of Hg in water and soil will greatly improve the flux estimate. Elucidation on the kinetics and mechanism of Hg(II) reduction in soil/water and quantification of the surface resistances specific to Hg species will also help reduce the model uncertainty.
We review lattice results related to pion, kaon,
D
- and
B
-meson physics with the aim of making them easily accessible to the particle-physics community. More specifically, we report on the ...determination of the light-quark masses, the form factor
f
+
(
0
)
, arising in the semileptonic
K
→
π
transition at zero momentum transfer, as well as the decay constant ratio
f
K
/
f
π
and its consequences for the CKM matrix elements
V
u
s
and
V
u
d
. Furthermore, we describe the results obtained on the lattice for some of the low-energy constants of
S
U
(
2
)
L
×
S
U
(
2
)
R
and
S
U
(
3
)
L
×
S
U
(
3
)
R
Chiral Perturbation Theory. We review the determination of the
B
K
parameter of neutral kaon mixing as well as the additional four
B
parameters that arise in theories of physics beyond the Standard Model. The latter quantities are an addition compared to the previous review. For the heavy-quark sector, we provide results for
m
c
and
m
b
(also new compared to the previous review), as well as those for
D
- and
B
-meson-decay constants, form factors, and mixing parameters. These are the heavy-quark quantities most relevant for the determination of CKM matrix elements and the global CKM unitarity-triangle fit. Finally, we review the status of lattice determinations of the strong coupling constant
α
s
.
Summary
Background Hand‐foot skin reaction is a distinctive cutaneous side‐effect of antineoplastic kinase inhibitor‐targeted therapy. Severe hand‐foot skin reaction requires postponement of ...treatment or dose reduction. Histopathological studies of skin toxicity associated with kinase inhibitors are currently unavailable.
Objectives To report the clinical and histopathological findings of hand‐foot skin reaction produced by the multikinase inhibitor sorafenib.
Methods Nine patients with metastatic carcinoma—seven with renal cell carcinoma (RCC), one with melanoma and one with hepatocellular carcinoma (HCC)—received continuous, oral sorafenib 400 mg twice daily. Hand‐foot skin reaction was defined and graded according to National Cancer Institute Common Toxicity Criteria 3.0. Biopsies from lesions of erythematous scaly or blistering skin were obtained from five cases (four RCC and one HCC).
Results Seven of the nine (78%) patients developed hand‐foot skin reaction characterized by well‐demarcated, tender, erythematous papules and plaques with greyish blisters or hyperkeratotic, callus‐like formations on palmoplantar surfaces and distal phalanges. Skin biopsy of hand‐foot skin reaction lesions revealed epidermal acanthosis, papillomatosis, parakeratosis, dispersed dyskeratotic cells and keratinocyte vacuolar degeneration. Other skin toxicities included angular cheilitis, seborrhoeic dermatitis and perianal dermatitis.
Conclusions The clinical manifestations and histopathological features of sorafenib‐induced skin reactions are unique. The most relevant histopathological findings of hand‐foot skin reaction include keratinocyte vacuolar degeneration, the presence of intracytoplasmic eosinophilic bodies, and intraepidermal blisters in the stratum malpighii. Further studies are warranted to elucidate the mechanisms of this novel multitargeted kinase inhibitor‐associated skin reaction.
This work reports a precise measurement of the reactor antineutrino flux using 2.2 million inverse beta decay (IBD) events collected with the Daya Bay near detectors in 1230 days. The dominant ...uncertainty on the neutron detection efficiency is reduced by 56% with respect to the previous measurement through a comprehensive neutron calibration and detailed data and simulation analysis. The new average IBD yield is determined to be (5.91±0.09)×10−43 cm2/fission with total uncertainty improved by 29%. The corresponding mean fission fractions from the four main fission isotopes U235, U238, Pu239, and Pu241 are 0.564, 0.076, 0.304, and 0.056, respectively. The ratio of measured to predicted antineutrino yield is found to be 0.952±0.014±0.023 (1.001±0.015±0.027) for the Huber-Mueller (ILL-Vogel) model, where the first and second uncertainty are experimental and theoretical model uncertainty, respectively. This measurement confirms the discrepancy between the world average of reactor antineutrino flux and the Huber-Mueller model.
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