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.

[Investigation of the cognition and behavior on drug safety in Beijing middle school students].

OBJECTIVE: To understand the cognition and behavior of drug safety in Beijing middle school students and provide advice for relevant education. METHODS: A cross-sectional survey using paper questionnaires was carried out on the student body of nine Beijing middle schools. Multi-stage proportionate stratified cluster sampling was adopted to enroll participants. In addition to demographic questions, the questionnaire included 17 questions assessing the cognition and behavior of safe drug use, prioritizing questions that aligned with the health education guideline for primary and secondary school students from Chinese Ministry of Education. Descriptive statistical methods were applied using the SAS 9.2 software. RESULTS: Of the 4 220 students investigated, 2 097(49.7%) were males and 2 123(50.3%) were females. The average age was (14.3±1.7) years. 2 030(48.1%) students were from downtown areas, 1 511(35.8%) were from urban-rural linking areas and 679(16.1%) were from rural areas. Half (51.5%) of the respondents were junior high school students, and the others were from senior high schools (34.2%) and vocational high schools (14.3%). Most of the students (89.6%) lived off campus. The awareness rate of drug safety knowledge was 74.4%, the median score of drug safety behavior was 4 points (full score was 5 points) and there was a statistically positive correlation between the two (Spearman's correlation coefficient was 0.156, P<0.001). Both the awareness rates and the drug safety behavior scores were statistically different among the students in different regions, different school types and different residence types (P<0.001). Multiple factors analysis demonstrated the correlation between the cognition degrees of both drug safety knowledge, behavior and the above factors. Of all the students, 80.4% agreed that any drug could have adverse drug reactions; 40.5% were aware that antibiotics couldn't kill viruses; as many as 49.6% mistook aspirin as antibiotic; 97.4% would read drug instructions before taking them; Only 42.4% put expired drugs into special recycling bins; 49.8% would deviate from the suggested dosage and frequency of their medication when they were sick with common diseases. CONCLUSION: Overall, the cognition of drug safety in Beijing middle school students is good, but problems still exist in medication adherence, the management of expired drugs and the antibiotics cognition, which need to be fixed through specific, pointed way of education. And more efforts should be made to improve the cognition in rural regions, vocational high schools and on campus students.

Heritability of young- and old-onset ischaemic stroke.

BACKGROUND AND PURPOSE: Although the genetic contribution to stroke risk is well known, it remains unclear if young-onset stroke has a stronger genetic contribution than old-onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole-genome array data in population-based samples. METHODS: This analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young-onset stroke (age < 55 years). To quantify the heritability for stroke risk in these unrelated individuals, the pairwise genetic relatedness was estimated between individuals based on their whole-genome array data using a mixed linear model. Heritability was estimated separately for young-onset stroke and old-onset stroke (age ≥ 55 years). RESULTS: Heritabilities for young-onset stroke and old-onset stroke were estimated at 42% (±8%, P < 0.001) and 34% (±10%, P < 0.001), respectively. CONCLUSIONS: Our data suggest that the genetic contribution to the risk of stroke may be higher in young-onset ischaemic stroke, although the difference was not statistically significant.

Activity and mechanism of action of HDVD, a novel pyrimidine nucleoside derivative with high levels of selectivity and potency against gammaherpesviruses.

A novel nucleoside analogue, 1-[(2S,4S-2-(hydroxymethyl)-1,3-dioxolan-4-yl]5-vinylpyrimidine-2,4(1H,3H)-dione, or HDVD, was evaluated against a wide variety of herpesviruses and was found to be a highly selective inhibitor of replication of the gammaherpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). HDVD had also a pronounced inhibitory activity against murine herpesvirus 68 (MHV-68) and herpes simplex virus 1 (HSV-1). In contrast, replication of herpesvirus saimiri (HVS), HSV-2, and varicella-zoster virus (VZV) was weakly inhibited by the compound, and no antiviral activity was determined against human cytomegalovirus (HCMV) and rhesus rhadinovirus (RRV). The HDVD-resistant virus phenotype contained point mutations in the viral thymidine kinase (TK) of HSV-1, MHV-68, and HVS isolates. These mutations conferred cross-resistance to other TK-dependent drugs, with the exception of an MHV-68 mutant (E358D) that exhibited resistance only to HDVD. HSV-1 and HVS TK-mutants isolated under selective pressure with bromovinyldeoxyuridine (BVDU) also showed reduced sensitivity to HDVD. Oral treatment with HDVD and BVDU was assessed in an intranasal model of MHV-68 infection in BALB/c mice. In contrast to BVDU treatment, HDVD-treated animals showed a reduction in viral DNA loads and diminished viral gene expression during acute viral replication in the lungs in comparison to levels in untreated controls. The valyl ester prodrug of HDVD (USS-02-71-44) suppressed the latent infection in the spleen to a greater extent than HDVD. In the present study, HDVD emerged as a highly potent antiviral with a unique spectrum of activity against herpesviruses, in particular, gammaherpesviruses, and may be of interest in the treatment of virus-associated diseases.

Beam focalization in reflection from flat dielectric subwavelength gratings.

We experimentally demonstrate the recently predicted effect of near-field focusing for light beams from flat dielectric subwavelength gratings (SWGs). This SWGs were designed for visible light 532 nm and fabricated by direct laser writing in a negative photoresist, with the refractive index n=1.5 and the period d=314 nm. The laterally invariant gratings can focus light beams without any optical axis to achieve the transversal invariance. We show that focal distances can be obtained up to 13 µm at normal reflection for TE polarization.

Improving susceptibility mapping using a threshold-based K-space/image domain iterative reconstruction approach.

To improve susceptibility quantification, a threshold-based k-space/image domain iterative approach that uses geometric information from the susceptibility map itself as a constraint to overcome the ill-posed nature of the inverse filter is introduced. Simulations were used to study the accuracy of the method and its robustness in the presence of noise. In vivo data were processed and analyzed using this method. Both simulations and in vivo results show that most streaking artifacts inside the susceptibility map caused by the ill-defined inverse filter were suppressed by the iterative approach. In simulated data, the bias toward lower mean susceptibility values inside vessels has been shown to decrease from around 10% to 2% when choosing an appropriate threshold value for the proposed iterative method. Typically, three iterations are sufficient for this approach to converge and this process takes less than 30 s to process a 512×512×256 dataset. This iterative method improves quantification of susceptibility inside vessels and reduces streaking artifacts throughout the brain for data collected from a single-orientation acquisition. This approach has been applied to vessels alone as well as to vessels and other structures with lower susceptibility to generate whole brain susceptibility maps with significantly reduced streaking artifacts.

Nanostructured silicon surface modifications for as a selective matrix-free laser desorption/ionization mass spectrometry.

Matrix-assisted laser desorption/ionization mass spectrometry is an established soft ionization method that is widely applied to analyze biomolecules. The UV-absorbing organic matrix is essential for biomolecule ionization; however, it also creates matrix background interference, which results in problematic analyses of biomolecules of less than 700 Da. Therefore, this study investigates hydrophilic, hydrophobic cationic, anionic and immobilized metal ion surface chemical modifications to advance nanostructured silicon mass spectrometry performance (nSi-MS). This investigation provides information required for a possible novel mass spectroscopy that combines surface-enhanced and nanostructured silicon surface-assisted laser desorption/ionization mass spectrometry for the selective detection of specific compounds of a mixture.

A new automatic algorithm to extract craniofacial measurements from fetal three-dimensional volumes.

OBJECTIVES: Three-dimensional (3D) ultrasound is useful in the prenatal evaluation of fetal craniofacial structures, particularly as it provides a multiplanar view. However, an expert must designate the area of interest and the appropriate view, making measurement of fetal structures using 3D ultrasound both time-consuming and subjective. In this study we propose an image analysis system that measures automatically and precisely the fetal craniofacial structures and evaluate its performance in the second trimester of pregnancy using a new 3D volume analysis algorithm. METHODS: A universal facial surface template model containing the geometric shape information of a fetal craniofacial structure was constructed from a fetal phantom. Using the proposed image analysis system we fitted this stored template model using a model deformation approach to individual fetal 3D facial volumes from 11 mid-trimester fetuses, and extracted automatically the following standard measurements: biparietal diameter (BPD), occipitofrontal diameter (OFD), interorbital diameter (IOD), bilateral orbital diameter (BOD) and distance between vertex and nasion (VN). The same five parameters were measured manually by an expert and the results compared. RESULTS: Comparison of the algorithm-based automatic measurements with manual measurements made by an expert gave correlation coefficients of 0.99 for BPD, 0.98 for OFD, 0.80 for BOD, 0.83 for IOD and 0.99 for VN. There were no significant differences between automatic and manual measurements. CONCLUSION: Our proposed system measures precisely the fetal craniofacial structures using 3D ultrasound, making it potentially useful for clinical service. This system could also be applied to other clinical fields in future testing.

Noninvasive cutaneous blood flow as a response predictor for visible light therapy on segmental vitiligo: a prospective pilot study.

BACKGROUND: Visible light is a treatment option for segmental vitiligo (SV), and visible light-induced repigmentation is associated with normalization of sympathetic dysfunction. Currently, it is difficult to predict individual patients' response to visible light therapy. OBJECTIVES: To test whether cutaneous blood flow can serve as a response predictor for visible light on treating SV. METHODS: Fourteen patients with SV were recruited in this prospective pilot study. Laser Doppler flowmetry was used to evaluate the cutaneous blood flow over SV lesions and contralateral normal skin. The pretreatment blood flow evaluation consisted of two stages: stage 1, following cold stress without prior visible light irradiation, and stage 2, following cold stress with prior visible light irradiation. Subsequently, the patients received regular visible light treatment for 3months, and a comparison of the pretreatment blood flow patterns between the visible light responding and nonresponding groups was carried out at the end of the study period. RESULTS: The SV lesions showed different blood flow profiles as compared with the contralateral normal skin. At the end of the 3-month study period, seven (50%) patients showed clinical repigmentation of >25%. The visible light responding group showed a more consistent occurrence of increased blood flow after stage 2 of the pretreatment evaluation while the nonresponding counterpart showed no significant changes. CONCLUSIONS: Normalization of sympathetic dysfunction may account for the efficacy of visible light in treating SV. Evaluation of cutaneous blood flow with and without prior visible light irradiation on cold-stressed SV lesions may serve as a treatment response predictor.

GaN epitaxial layers prepared on nano-patterned Si(001) substrate.

We report the growth of GaN epitaxial layer on Si(001) substrate with nano-patterns prepared by dry etching facility used in integrated circuit (IC) industry. It was found that the GaN epitaxial layer prepared on nano-patterned Si(001) substrate exhibits both cubic and hexagonal phases. It was also found that threading dislocation observed from GaN prepared on nano-patterned Si(001) substrate was significantly smaller than that prepared on conventional unpatterned Si(111) substrate. Furthermore, it was found that we can reduce the tensile stress in GaN epitaxial layer by about 78% using the nano-patterned Si(001) substrate.

Oral Nutritional Supplement with ß-hydroxy-ß-methylbutyrate (HMB) Improves Nutrition, Physical Performance and Ameliorates Intramuscular Adiposity in Pre-Frail Older Adults: A Randomized Controlled Trial.

OBJECTIVES: Supplementation of high protein oral nutrition shakes supplemented with ß-hydroxy-ß-methylbutyrate (HP-HMB) has been shown to improve muscle mass, muscle strength, and physical performance in older adults, but the roles of HP-HMB supplementation on the intramuscular adiposity remained unknown. This 12-week randomized controlled trial evaluated the changes of muscle mass, muscle strength, physical performance and intramuscular adiposity among community-dwelling pre-frail older persons. METHODS: This was an open-label, parallel group, randomized controlled trail that enrolled 70 community-dwelling pre-frail older persons without active or uncontrolled conditions, disability or dementia. The intervention group was provided with two services of HP HMB (Ensure® Plus Advance containing 3g HMB) per day for 12 weeks, and the control group was provided with professional nutritional counselling for sufficient protein intake. All participants received functional assessments, laboratory tests and magnetic resonance imaging (MRI) of the dominant leg before and after study. Intramuscular adipose tissue (IMAT) and the mid-thigh cross-sectional area (CSA) of muscle were obtained by MRI, and the IMAT-to-CSA ratio was calculated to evaluate intramuscular adiposity. RESULTS: Overall, 62 participants (mean age: 71.1±3.8 years, 69.4% female) completed the study (HP-HMB group: 29, control group: 33) and comparisons of baseline characteristics between groups were not statistically different. For the primary outcome, HP-HMB group showed significant improvements in the CSA of mid-thigh muscle (mean increase of CSA: 149.1±272.3 for HMB group vs -22.9±309.1 mm2 for control group, P=0.045). The improvement of MNA-SF was borderline (0.28±0.75 vs. -0.15±0.94, P=0.064), but serum levels of Vit D were significantly increased in the HMB group (3.83±8.18 vs. -1.30±4.81 ng/mL, P=0.002). Moreover, the body weight and BMI were significantly increased in the HMB group (1.10±1.18 vs. 0.24±1.13 kg, P=0.005; 0.56±0.68 vs. 0.22±0.47 kg/m2, P=0.019). In particular, the IMAT-to-CSA ratio was reduced in the HMB group (-0.38±1.21 vs. -0.02±2.56 %, P=0.06). Using the generalized estimating equation, we found that SPPB score in chair rise test was significantly improved (ß=0.71, 95% C.I.0.09-1.33, P=0.026). CONCLUSIONS: The 12-week supplementation with high protein oral nutrition shake supplemented with 3g HMB per day significantly increased muscle mass, as well as nutritional status and physical performance, and ameliorated the intramuscular adiposity of pre-frail older persons. Further study is needed to explore the long-term benefits of HP-HMB supplementation on muscle and metabolic health for older adults.

Addition of GM-CSF to trastuzumab stabilises disease in trastuzumab-resistant HER2+ metastatic breast cancer patients.

BACKGROUND: One of the proposed mechanisms of trastuzumab-induced regression of human epidermal growth factor receptor 2-positive (HER2+) tumours includes facilitation of antibody-dependent cell-mediated cytotoxicity (ADCC). Granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates ADCC. We presented our pilot study of adding GM-CSF to trastuzumab in patients with trastuzumab-resistant HER2+ metastatic breast cancer. METHODS: Patients with HER2+ metastatic breast cancer that progressed after trastuzumab +/- chemotherapy were continued on trastuzumab 2 mg kg(-1) intravenous weekly and GM-CSF 250 µg m(-2) subcutaneous daily. Patients were assessed for response every 8 weeks. Treatment was continued until disease progression or intolerable toxicity. RESULTS: Seventeen patients were evaluable (median age 48 years, range 27-75 years). The median number of metastatic sites was 2 (range 1-3); the most common site was the liver (n=10). The median number of prior regimens for metastatic disease was 2 (range 1-5). No objective disease response was observed, but five patients (29%) had stable disease for a median duration of 15.8 (range 10-53.9) weeks. The most common adverse event was rash at the injection site. No grade 4 or irreversible adverse event was seen. CONCLUSION: The addition of GM-CSF to trastuzumab alone had a modest clinical benefit and acceptable safety profile in heavily pretreated patients with trastuzumab-resistant HER2+ metastatic breast cancer.

Susceptibility mapping as a means to visualize veins and quantify oxygen saturation.

PURPOSE: To create an orientation-independent, 3D reconstruction of the veins in the brain using susceptibility mapping. MATERIALS AND METHODS: High-resolution, high-pass filtered phase images usually used for susceptibility weighted imaging (SWI) were used as a source for local magnetic field behavior. These images were subsequently postprocessed using an inverse procedure to generate susceptibility maps of the veins. Regularization and interpolation of the data in k-space of the phase images were used to reduce reconstruction artifacts. To understand the effects of artifacts, and to fine-tune the methodology, simulations of blood vessels were performed with and without noise. RESULTS: With sufficient resolution, major veins in the brain could be visualized with this approach. The usual geometry-dependent phase dipole effects are removed by this processing, leaving basically images of the veins. Different sized vessels show a different level of contrast depending on their partial volume effects. Vessels that are 8 mm or 16 mm in size show quantitative values expected for normal oxygen saturation levels. Smaller vessels show smaller values due to errors in the methodology and due to partial volume effects. Larger vessels show a bias toward a reduced susceptibility approaching 90% of the expected value. Limitations of the method and artifacts related to different sources of errors are demonstrated. CONCLUSION: Susceptibility maps can successfully create venograms of the brain with varying levels of contrast-to-noise depending on the size of the vessel. Partial volume effects render this approach more useful as an imaging tool or a visualization tool, although certain larger vessels have measured susceptibilities close to expected values associated with normal blood oxygen saturation levels.

Quaternary ZnCdSeTe nanowires.

We report the growth of needle-like high density quaternary ZnCdSeTe nanowires on oxidized Si(100) substrate using vapor-liquid-solid mechanism by molecular beam epitaxy with an Au-based nanocatalyst. It was found that average length and average diameter of the nanowires were 1.3 microm and 91 nm, respectively. It was also found that the as-grown ZnCdSeTe nanowires exhibit mixture of cubic zinc-blende and hexagonal wurtzite structures. Energy depersive results indicate that composition ratio of our nanowire should be Zn0.87Cd0.13Se0.98Te0.02, which agrees excellently with the designated composition ratio of Zn0.87Cd0.13Se0.98Te0.02.

Changes in physicochemical properties of egg white and yolk proteins from duck shell eggs due to hydrostatic pressure treatment.

The shell of the duck egg did not crack after pressure treatments (300 to 500 MPa; 25 degrees C; 10 min) in this study; therefore, the changes of physicochemical properties of egg white and yolk proteins from the intact shell egg by pressure treatment were first investigated and compared with those of pressurized hen liquid eggs. Although the proximate compositions of duck eggs and hen eggs were similar, the moisture and protein contents of hen whole eggs were higher than those of duck whole eggs. The protein contents of duck egg white and yolk were slightly lower than those of hen eggs, and the moisture content of duck egg white was equal to that of hen egg white, whereas that of duck egg yolk was lower than that of hen egg yolk. After pressure treatment at 500 MPa, the results of solubility, sulfhydryl content, surface hydrophobicity, and residual denaturation enthalpy showed that egg white proteins underwent slight but significant unfolding and aggregation, whereas pressure treatments below 500 MPa induced insignificant changes in the physicochemical properties. On the other hand, pressure treatments at 400 and 500 MPa significantly reduced the solubility and residual denaturation enthalpy of egg yolk proteins. However, the native PAGE result showed that pressure treatment up to 500 MPa did not affect the protein components of egg white and yolk. The results showed that the application of pressure treatment on duck shell egg may induce reversible denaturation of both egg white and yolk proteins. The egg white and yolk proteins may be prevented from denaturation after pressure treatment in the presence of the eggshell compared with the absence of the eggshell. As reported in the literature, pressure treatments at 300 to 500 MPa and 25 degrees C would be efficient for decontamination of duck shell eggs. Therefore, based on the consideration for food safety and functional properties, pressure processing can be a good preservation technique for duck shell eggs.

Antisense oligonucleotides as therapeutic agents--is the bullet really magical?

Because of the specificity of Watson-Crick base pairing, attempts are now being made to use oligodeoxynucleotides (oligos) in the therapy of human disease. However, for a successful outcome, the oligo must meet at least six criteria: (i) the oligos can be synthesized easily and in bulk; (ii) the oligos must be stable in vivo; (iii) the oligos must be able to enter the target cell; (iv) the oligos must be retained by the target cell; (v) the oligos must be able to interact with their cellular targets; and (vi) the oligos should not interact in a non-sequence-specific manner with other macromolecules. Phosphorothioate oligos are examples of oligos that are being considered for clinical therapeutic trials and meet some, but not all, of these criteria. The potential use of phosphorothioate oligos as inhibitors of viral replication is highlighted.

Epstein-Barr virus: inhibition of replication by three new drugs.

Epstein-Barr virus (EBV) is the cause of infectious mononucleosis and is associated with three human malignancies. Acyclovir [9-(2-hydroxyethoxymethyl)guanine], the first clinically useful drug effective against replication of EBV, is without effect against latent or persistent EBV infection. Three nucleoside analogs, E-5-(2-bromovinyl)-2'-deoxyuridine, 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine, and 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-methyluracil are potent inhibitors of EBV replication in vitro. Moreover, in contrast to the reversibility of viral inhibition by Acyclovir, these three drugs have prolonged effects in suppressing viral replication even after the drugs are removed from persistently infected cell cultures.