Search for a Sub-eV Sterile Neutrino Using Daya Bay's Full Dataset.

This Letter presents results of a search for the mixing of a sub-eV sterile neutrino with three active neutrinos based on the full data sample of the Daya Bay Reactor Neutrino Experiment, collected during 3158 days of detector operation, which contains 5.55×10^{6} reactor ν[over ¯]_{e} candidates identified as inverse beta-decay interactions followed by neutron capture on gadolinium. The analysis benefits from a doubling of the statistics of our previous result and from improvements of several important systematic uncertainties. No significant oscillation due to mixing of a sub-eV sterile neutrino with active neutrinos was found. Exclusion limits are set by both Feldman-Cousins and CLs methods. Light sterile neutrino mixing with sin^{2}2θ_{14}≳0.01 can be excluded at 95% confidence level in the region of 0.01 eV^{2}≲|Δm_{41}^{2}|≲0.1 eV^{2}. This result represents the world-leading constraints in the region of 2×10^{-4} eV^{2}≲|Δm_{41}^{2}|≲0.2 eV^{2}.

Improved Measurement of the Evolution of the Reactor Antineutrino Flux and Spectrum at Daya Bay.

Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.

Precision Measurement of Reactor Antineutrino Oscillation at Kilometer-Scale Baselines by Daya Bay.

We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3} eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3} eV^{2} for the inverted mass ordering.

First Measurement of High-Energy Reactor Antineutrinos at Daya Bay.

This Letter reports the first measurement of high-energy reactor antineutrinos at Daya Bay, with nearly 9000 inverse beta decay candidates in the prompt energy region of 8-12 MeV observed over 1958 days of data collection. A multivariate analysis is used to separate 2500 signal events from background statistically. The hypothesis of no reactor antineutrinos with neutrino energy above 10 MeV is rejected with a significance of 6.2 standard deviations. A 29% antineutrino flux deficit in the prompt energy region of 8-11 MeV is observed compared to a recent model prediction. We provide the unfolded antineutrino spectrum above 7 MeV as a data-based reference for other experiments. This result provides the first direct observation of the production of antineutrinos from several high-Q_{ß} isotopes in commercial reactors.

Cymbopogom Citratus Essential Oils: A Promising Source of Antifungals Against Panax Notoginseng-Associated Pathogenic Fungi.

Due to the great threat of chemical pesticides to the ecosystem environment, it is a long-term goal to find environmentally friendly green pesticides. Essential oils (EOs) are considered weapons in plant chemical defense and are important sources of green pesticides. Therefore, the antifungal effects and action mechanisms of Cymbopogom citratus (C. citratus) EOs against seven kinds of Panax notoginseng (P. notoginseng) pathogenic fungi were investigated. Oxford Cup results showed that C. citratus EOs had an excellent detraction effects against seven fungi of P. notoginseng. Gas chromatography-mass spectrometry (GC-MS) was used to construct the chemical profiles of C. citratus EOs, disclosed that the main categories are terpenes and oxygenated terpenes. In addition, compared with the hymexazol, the minimum inhibitory concentration (MIC) showed that EOs and their main components had strong antifungal activities. Besides, EOs had a synergistic effect with hymexazol (a chemical pesticide). The antifungal mechanism of C. citratus EOs was studied by using Fusarium oxysporum (F. oxysporum) as the dominant pathogen. C. citratus EOs may affect the metabolism of fungi and induce mycotoxins to destroy the cell wall to achieve antifungal effects. Finally, EOs were found to significantly retard P. notoginseng infection by F. oxysporum. According to our research, C. citratus EOs are potential green antifungal agent that can be used in the cultivation of P. notoginseng.

Extraction of the

This Letter reports the first extraction of individual antineutrino spectra from ^{235}U and ^{239}Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at Daya Bay. The analysis uses 3.5×10^{6} inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, ^{235}U and ^{239}Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the ^{235}U (^{239}Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for ^{235}U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.

[Detection and analysis of FAM19A4 promoter methylation in cervical exfoliated cells].

Objective: To investigate the cinical value of FAM19A4promoter methylation in cervicalexfoliated cells for triage of cervical cancer. Methods: A total of 162 high-risk HPV-infected patients who were pathologically confirmed as different cervical lesions from August 2017 to December 2017 were collected in Guangdong Women and Children Hospital. Taqman probe-based quantitative PCR (qPCR) was used to detect the methylation of FAM19A4 promoterin different grades of cervical lesions, and the value of FAM19A4 methylation in predicting cervical HSIL and the above lesions was calculated by diagnostic test. Results: (1)The positive rates of FAM19A4 methylation in cervical exfoliated cells increased with the severity of cervical lesions, which were 7.69% (4/52) , 34.62% (9/26) , 55.56% (20/36) , 95.83% (46/48) in normal cervix/cervicitis, cervical LSIL, HSIL, and cervical cancer, respectively(P<0.05).(2)There was no significant difference in the detection rates of FAM19A4 methylation between different age groups, pathological types, clinical stage, tumor size and lymph node metastasis status (P>0.05). (3) The specificity and positive predictive value of FAM19A4 methylation in detecting cervical HSIL alone and ≥HSIL lesions were the optimal, with the AUC of 0.69 and 0.84, respectively. When combined with HPV16/18 genotyping, the sensitivity was significantly improved. Conclusions: The detection of FAM19A4 promoter methylation in cervical exfoliated cells has a high clinical value of discriminating ≥HSIL lesions; and the cotest of methylated FAM19A4 and HPV16/18 genotyping can identify ≥HSIL lesions more sensitively.

Measurement of the Electron Antineutrino Oscillation with 1958 Days of Operation at Daya Bay.

We report a measurement of electron antineutrino oscillation from the Daya Bay Reactor Neutrino Experiment with nearly 4 million reactor ν[over ¯]_{e} inverse ß decay candidates observed over 1958 days of data collection. The installation of a flash analog-to-digital converter readout system and a special calibration campaign using different source enclosures reduce uncertainties in the absolute energy calibration to less than 0.5% for visible energies larger than 2 MeV. The uncertainty in the cosmogenic ^{9}Li and ^{8}He background is reduced from 45% to 30% in the near detectors. A detailed investigation of the spent nuclear fuel history improves its uncertainty from 100% to 30%. Analysis of the relative ν[over ¯]_{e} rates and energy spectra among detectors yields sin^{2}2θ_{13}=0.0856±0.0029 and Δm_{32}^{2}=(2.471_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the normal hierarchy, and Δm_{32}^{2}=-(2.575_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the inverted hierarchy.

Evolution of the Reactor Antineutrino Flux and Spectrum at Daya Bay.

The Daya Bay experiment has observed correlations between reactor core fuel evolution and changes in the reactor antineutrino flux and energy spectrum. Four antineutrino detectors in two experimental halls were used to identify 2.2 million inverse beta decays (IBDs) over 1230 days spanning multiple fuel cycles for each of six 2.9 GW_{th} reactor cores at the Daya Bay and Ling Ao nuclear power plants. Using detector data spanning effective ^{239}Pu fission fractions F_{239} from 0.25 to 0.35, Daya Bay measures an average IBD yield σ[over ¯]_{f} of (5.90±0.13)×10^{-43} cm^{2}/fission and a fuel-dependent variation in the IBD yield, dσ_{f}/dF_{239}, of (-1.86±0.18)×10^{-43} cm^{2}/fission. This observation rejects the hypothesis of a constant antineutrino flux as a function of the ^{239}Pu fission fraction at 10 standard deviations. The variation in IBD yield is found to be energy dependent, rejecting the hypothesis of a constant antineutrino energy spectrum at 5.1 standard deviations. While measurements of the evolution in the IBD spectrum show general agreement with predictions from recent reactor models, the measured evolution in total IBD yield disagrees with recent predictions at 3.1σ. This discrepancy indicates that an overall deficit in the measured flux with respect to predictions does not result from equal fractional deficits from the primary fission isotopes ^{235}U, ^{239}Pu, ^{238}U, and ^{241}Pu. Based on measured IBD yield variations, yields of (6.17±0.17) and (4.27±0.26)×10^{-43} cm^{2}/fission have been determined for the two dominant fission parent isotopes ^{235}U and ^{239}Pu. A 7.8% discrepancy between the observed and predicted ^{235}U yields suggests that this isotope may be the primary contributor to the reactor antineutrino anomaly.

Results from the Survey of Antibiotic Resistance (SOAR) 2012-14 in Thailand, India, South Korea and Singapore.

OBJECTIVES: To provide susceptibility data for community-acquired respiratory tract isolates of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Moraxella catarrhalis collected in 2012-14 from four Asian countries. METHODS: MICs were determined using Etest(®) for all antibiotics except erythromycin, which was evaluated by disc diffusion. Susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. For macrolide/clindamycin interpretation, breakpoints were adjusted for incubation in CO2 where available. RESULTS: Susceptibility of S. pneumoniae was generally lower in South Korea than in other countries. Penicillin susceptibility assessed using CLSI oral or EUCAST breakpoints ranged from 21.2% in South Korea to 63.8% in Singapore. In contrast, susceptibility using CLSI intravenous breakpoints was much higher, at 79% in South Korea and ∼95% or higher elsewhere. Macrolide susceptibility was ∼20% in South Korea and ∼50%-60% elsewhere. Among S. pyogenes isolates (India only), erythromycin susceptibility (∼20%) was lowest of the antibiotics tested. In H. influenzae antibiotic susceptibility was high except for ampicillin, where susceptibility ranged from 16.7% in South Korea to 91.1% in India. South Korea also had a high percentage (18.1%) of ß-lactamase-negative ampicillin-resistant isolates. Amoxicillin/clavulanic acid susceptibility for each pathogen (PK/PD high dose) was between 93% and 100% in all countries except for H. influenzae in South Korea (62.5%). CONCLUSIONS: Use of EUCAST versus CLSI breakpoints had profound differences for cefaclor, cefuroxime and ofloxacin, with EUCAST showing lower susceptibility. There was considerable variability in susceptibility among countries in the same region. Thus, continued surveillance is necessary to track future changes in antibiotic resistance.

Measurement of the Reactor Antineutrino Flux and Spectrum at Daya Bay.

This Letter reports a measurement of the flux and energy spectrum of electron antineutrinos from six 2.9 GWth nuclear reactors with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls in the Daya Bay experiment. Using 217 days of data, 296 721 and 41 589 inverse ß decay (IBD) candidates were detected in the near and far halls, respectively. The measured IBD yield is (1.55±0.04) ×10(-18) cm(2) GW(-1) day(-1) or (5.92±0.14) ×10(-43) cm(2) fission(-1). This flux measurement is consistent with previous short-baseline reactor antineutrino experiments and is 0.946±0.022 (0.991±0.023) relative to the flux predicted with the Huber-Mueller (ILL-Vogel) fissile antineutrino model. The measured IBD positron energy spectrum deviates from both spectral predictions by more than 2σ over the full energy range with a local significance of up to ∼4σ between 4-6 MeV. A reactor antineutrino spectrum of IBD reactions is extracted from the measured positron energy spectrum for model-independent predictions.

New measurement of antineutrino oscillation with the full detector configuration at Daya Bay.

We report a new measurement of electron antineutrino disappearance using the fully constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9×10^{5} GW_{th} ton days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six ^{241}Am-^{13}C radioactive calibration sources reduced the background by a factor of 2 for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of sin^{2}2θ_{13} and |Δm_{ee}^{2}| were halved as a result of these improvements. An analysis of the relative antineutrino rates and energy spectra between detectors gave sin^{2}2θ_{13}=0.084±0.005 and |Δm_{ee}^{2}|=(2.42±0.11)×10^{-3} eV^{2} in the three-neutrino framework.

Epidermal necrolysis: 60 years of errors and advances.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare conditions characterized by extensive epidermal detachment and mucositis. Both are associated with a high mortality rate and significant long-term morbidity. Since the initial report introducing the term TEN in 1956, diagnosis of the condition has been fraught with difficulties that continue to exist today. The terms 'erythema multiforme major' (EMM) and SJS, and their relationship to TEN have also been confusing to clinicians. It is now recognized that EMM is a different entity from SJS and TEN in terms of demographics, causality and severity. SJS and TEN represent a continuum of disease, and differ only by the extent of epidermal detachment and therefore severity. The term 'epidermal necrolysis' (EN) is used in this article to describe the spectrum of disease that includes SJS and TEN. Important advances in understanding the pathomechanism and treatment of EN have been made over the years. These include the recognition of human leucocyte antigen (HLA) associations (e.g. HLA-B*1502 with carbamazepine-induced TEN) and understanding of the pathogenic roles of drug-specific cytotoxic T cells and granulysin. It was previously believed that widespread keratinocyte death in EN is predominantly mediated by soluble Fas-ligand and that intravenous immunoglobulin therapy is useful in blocking this mechanism with resultant survival benefits. Further studies have since proven these theories to be incorrect. This short review describes the key advances in the terminology, classification, causality and treatment of EN, and identifies future priorities and challenges in the understanding and management of this condition.

An update of fixed drug eruptions in Singapore.

BACKGROUND: Fixed drug eruptions (FDE) are most commonly caused by antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs). The list of causative drugs changes with time and prescribing patterns but there has been no recent data on FDE seen in an outpatient setting in Singapore. OBJECTIVE: We aimed to evaluate the epidemiology, clinical features and causative drugs in patients with FDE in Singapore. METHODS: We performed a retrospective chart review of all patients seen with suspected FDE in the National Skin Centre, Singapore between 2008 and 2012. Using criteria adapted from the WHO-UMC causality assessment criteria, patients were classified into categories of definite (confirmed with patch test or drug provocation test), probable (causative drug identified based on patient's history), possible (clinically consistent but unable to identify causative drug) or unlikely FDE. RESULTS: We reviewed the charts of 126 patients who were seen for suspected FDE. Ten patients (7.0%) were classified as having definite FDE, 52 patients (41.3%) probable FDE, 61 patients (48.4%) possible FDE and three patients (2.4%) unlikely FDE. Clinical features were similar to those described in previous studies. Among the 62 patients with definite or probable FDE, etoricoxib was the most common cause (24 patients, 38.7%). Other common causes included paracetamol, other NSAIDs and doxycycline. Antihistamines caused FDE in three patients. CONCLUSION: Etoricoxib was the most frequent cause of FDE in our study. Other NSAIDs, paracetamol and doxycycline remain common causes of FDE but we caution that antihistamines, such as cetirizine, should also be considered.

Search for a light sterile neutrino at Daya Bay.

A search for light sterile neutrino mixing was performed with the first 217 days of data from the Daya Bay Reactor Antineutrino Experiment. The experiment's unique configuration of multiple baselines from six 2.9 GW(th) nuclear reactors to six antineutrino detectors deployed in two near (effective baselines 512 m and 561 m) and one far (1579 m) underground experimental halls makes it possible to test for oscillations to a fourth (sterile) neutrino in the 10(-3) eV(2)<|Δm(41)(2) |< 0.3 eV(2) range. The relative spectral distortion due to the disappearance of electron antineutrinos was found to be consistent with that of the three-flavor oscillation model. The derived limits on sin(2) 2θ(14) cover the 10(-3) eV(2) ≲ |Δm(41)(2)| ≲ 0.1 eV(2) region, which was largely unexplored.

A novel nonsense mutation in the EpCAM gene in a patient with congenital tufting enteropathy.

OBJECTIVES: Tufting enteropathy (TE) is a classical congenital disorder of the intestinal mucosa causing protracted diarrhea in infancy as a result of a dysfunctional epithelial cell barrier, which is mainly caused by mutations in the EpCAM gene and expression of a nonfunctional epithelial cell adhesion molecule in the intestine. We report here a novel nonsense mutation in a patient suspected of having TE, resulting in a complete absence of EpCAM in duodenal enterocytes. METHODS: A patient presenting with congenital diarrhea and suspected of having TE was screened for EpCAM mutations, and duodenal biopsies were stained for EpCAM using immunohistochemistry analysis. RESULTS: We identified a novel homozygous nonsense mutation in the EpCAM gene in a patient suspected of having TE, causing a complete loss of EpCAM expression in duodenal enterocytes. CONCLUSIONS: With screening analysis for EpCAM mutations and immunohistochemistry for EpCAM expression in duodenal enterocytes, we found a novel homozygous mutation in a patient with classical protracted diarrhea in infancy finally diagnosed as TE, which results in a complete absence of EpCAM and in dysfunctional barrier formation in duodenal enterocytes.

Analysis of the interaction of tarantula toxin Jingzhaotoxin-III (ß-TRTX-Cj1α) with the voltage sensor of Kv2.1 uncovers the molecular basis for cross-activities on Kv2.1 and Nav1.5 channels.

Animal venoms contain a fascinating array of divergent peptide toxins that have cross-activities on different types of voltage-gated ion channels. However, the underlying mechanism remains poorly understood. Jingzhaotoxin-III (JZTX-III), a 36-residue peptide from the tarantula Chilobrachys jingzhao, is specific for Nav1.5 and Kv2.1 channels over the majority of other ion channel subtypes. JZTX-III traps the Nav1.5 DII voltage sensor at closed state by binding to the DIIS3-S4 linker. In this study, electrophysiological experiments showed that JZTX-III had no effect on five voltage-gated potassium channel subtypes (Kv1.4, Kv3.1, and Kv4.1-4.3), whereas it significantly inhibited Kv2.1 with an IC50 of 0.71 ± 0.01 µM. Mutagenesis and modeling data suggested that JZTX-III docks at the Kv2.1 voltage-sensor paddle. Alanine replacement of Phe274, Lys280, Ser281, Leu283, Gln284, and Val288 could decrease JZTX-III affinity by 7-, 9-, 34-, 12-, 9-, and 7-fold, respectively. Among them, S281 is the most crucial determinant, and the substitution with Thr only slightly reduced toxin sensitivity. In contrast, a single conversion of Ser281 to Ala, Phe, Ile, Val, or Glu increased the IC50 value by >34-fold. Alanine-scanning mutagenesis experiments indicated that the functional surface of JZTX-III bound to the Kv2.1 channel is composed of four hydrophobic residues (Trp8, Trp28, Trp30, and Val33) and three charged residues (Arg13, Lys15, and Glu34). The bioactive surfaces of JZTX-III interacting with Kv2.1 and Nav1.5 are only partially overlapping. These results strongly supported the hypothesis that animal toxins might use partially overlapping bioactive surfaces to target the voltage-sensor paddles of two different types of ion channels. Increasing our understanding of the molecular mechanisms of toxins interacting with voltage-gated sodium and potassium channels may provide new molecular insights into the design of more potent ion channel inhibitors.

Prevalence of chronic kidney disease in Jing adults in China: a village-based study.

AIM: Chronic kidney disease (CKD) is increasingly recognized as a predictor of end-stage renal and cardiovascular disease. There is no data on CKD prevalence in numerous minority communities of China such as the Guangxi Jing community. We determined CKD prevalence and related risk factors in Jing adults. METHODS: A stratified cluster random sampling method was used in this study comprising 757 Jing adults. Questionnaires, physical examinations and laboratory tests including measurements of urinary albumin and hematuria, were performed. Estimated glomerular filtration rate (eGFR) was calculated using the improved Chinese population MDRD formula. CKD-related risk factors were also examined. RESULTS: After standardization for age and gender, the prevalence of albuminuria, haematuria and eGFR < 60 ml/min per 1.73 m2 was 12.5%, 3.8% and 0.4%, respectively Overall CKD prevalence was 15.3%, while the awareness rate was only 11.6%. Females had a significantly higher (p < 0.05) prevalence of albuminuria, hematuria and eGFR < 60 ml/min compared to males. CKD prevalence tended to increase significantly (< 0.05) with increase in age. Using the standardized age and gender ratios, the prevalence of hypertension, diabetes, hyperlipidemia and hyperuricemia was 14.8%, 5.2%, 38% and 16.2%, respectively, with awareness of 41.0%, 41.2%, 6.6% and 0.9%. Prevalence of overweight or obesity status and metabolic syndrome was 12.1% and 3.0%. Females showed a significantly higher prevalence of hyperuricemia and obesity or overweight status. CKD prevalence was also significantly higher in people with risk diseases. Regression analysis showed that age, gender, hypertension, high cholesterol and diabetes were CKD-related risk factors, while culture (higher education level) was a protective factor. CONCLUSION: Jing adults showed a high CKD prevalence of 15.3%, with a low awareness rate of 11.6%. Older subjects and females were more susceptible with a high prevalence of hypertension, diabetes, hyperlipidemia, metabolic syndrome etc. being associated closely with CKD.