Abstract
Structural phase transitions serve as the basis for many functional applications including shape memory alloys (SMAs), switches based on metal-insulator transitions (MITs), etc. In such ...materials, lattice incompatibility between transformed and parent phases often results in a thermal hysteresis, which is intimately tied to degradation of reversibility of the transformation. The non-linear theory of martensite suggests that the hysteresis of a martensitic phase transformation is solely determined by the lattice constants, and the conditions proposed for geometrical compatibility have been successfully applied to minimizing the hysteresis in SMAs. Here, we apply the non-linear theory to a correlated oxide system (V
1−
x
W
x
O
2
), and show that the hysteresis of the MIT in the system can be directly tuned by adjusting the lattice constants of the phases. The results underscore the profound influence structural compatibility has on intrinsic electronic properties, and indicate that the theory provides a universal guidance for optimizing phase transforming materials.
Addition of cetuximab showed trend, but not significantly, to improve the therapeutic effects of gemcitabine and oxaliplatin combination for advanced biliary tract cancer in current randomized phase ...II trial. The trend of improvement did not correlate with KRAS mutation status. Biomarkers finding for selecting patients who will benefit most from anti-EGFR targeted therapy is warranted.
Previous clinical trials have not proved that adding epidermal growth factor receptor inhibitors to chemotherapy confers a survival benefit for patients with advanced biliary tract cancer (ABTC). Whether the KRAS mutation status of tumor cells confounded the results of past studies is unknown.
ABTC patients stratified by KRAS status, Eastern Cooperative Oncology Group performance status, and primary tumor location were randomized 1 : 1 to receive GEMOX (800 mg/m2 gemcitabine and 85 mg/m2 oxaliplatin) or C-GEMOX (500 mg/m2 cetuximab plus GEMOX) every 2 weeks. The primary end point was objective response rate (ORR).
The study enrolled 122 patients between December 2010 and May 2012 (62 treated with C-GEMOX and 60 with GEMOX). Compared with GEMOX alone, C-GEMOX was associated with trend to better ORR (27% versus 15%; P = 0.12) and progression-free survival (PFS, 6.7 versus 4.1 months; P = 0.05), but not overall survival (OS, 10.6 versus 9.8 months; P = 0.91). KRAS mutations, which were detected in 36% of tumor samples, did not affect the trends of difference in ORR and PFS between C-GEMOX and GEMOX. The two treatment arms had similar adverse events, except that more patients had skin rashes, allergic reactions, and neutropenia in the C-GEMOX arm. Of patients with C-GEMOX, the presence of a grade 2 or 3 skin rash was associated with significantly better ORR, PFS, and OS.
Addition of cetuximab did not significantly improve the ORR of GEMOX chemotherapy in ABTC, although a trend of PFS improvement was observed. The trend of improvement did not correlate with KRAS mutation status.
This study is registered at ClinicalTrials.gov (NCT01267344). All patients gave written informed consent.
Epidemiologic data on the etiologic organisms is important for appropriate empirical antibiotic treatment of bacterial meningitis. We identified the etiologies of community-acquired bacterial ...meningitis in Korean adults and the associated epidemiological factors. A retrospective, multicenter nationwide study was carried out. Patients 18 years of age or older with community-acquired bacterial meningitis with a confirmed pathogen were enrolled. Demographic, clinical, and microbiological data were collected. One hundred and ninety-five cases were collected. Streptococcus pneumoniae was the most common pathogen (50.8%), followed by Staphylococcus aureus (10.3%), Klebsiella pneumoniae (7.7%), Listeria monocytogenes (6.7%), and group B Streptococcus (3.1%). The penicillin resistance rate of the S. pneumoniae was 60.3%; 40.0% of the organisms were not susceptible to third-generation cephalosporins. The combination of third-generation cephalosporin with vancomycin was used in 76.3% of cases. Steroids were given before or with the first dose of antibiotics in 37.4% of patients. The 30-day mortality rate was 20.5% and neurological sequelae developed in 15.6% of cases. S. pneumoniae was the most common organism identified in community-acquired bacterial meningitis among Korean adults. S. aureus, K. pneumoniae, L. monocytogenes, and group B Streptococcus were also common. S. pneumoniae had high rates of resistance to penicillin and third-generation cephalosporins.
Background
There are few studies on the association between nutrient intake and telomere length, which may reflect cumulative oxidative stress and indicate biological ageing. In the present study, we ...evaluated longitudinal associations between the consumption of micronutrients, including antioxidant nutrients and B vitamins involved in one‐carbon transfer pathways, and leukocyte telomere length (LTL).
Methods
The study included 1958 middle‐aged and older Korean men and women (age range at baseline: 40–69 years) from a population‐based cohort. We collected dietary information at baseline using a semiquantitative food frequency questionnaire (June 2001 to January 2003) and assessed the consumption of micronutrients, including vitamins A, B1, B2, B3, B6, B9 (folate), C and E, as well as calcium, phosphorus, potassium, iron and zinc. We measured LTL using a real‐time polymerase chain reaction at the 10‐year follow‐up examination (February 2011 to November 2012).
Results
In the multiple regression model adjusted for potential confounders, LTL was positively associated with the consumption of vitamin C (P < 0.05), folate (P = 0.05) and potassium (P = 0.05) in all participants. In the age‐stratified analysis, the association between the consumption of vitamin C (P < 0.01), folate (P < 0.05) and potassium (P < 0.05) with LTL was significant only among participants aged <50 years.
Conclusions
Our findings suggest that the earlier consumption of vitamin C, folate and potassium, which are abundant in fruits and vegetables, can delay biological ageing in middle‐aged and older adults.
ABSTRACT
Many scientific investigations of photometric galaxy surveys require redshift estimates, whose uncertainty properties are best encapsulated by photometric redshift (photo-z) posterior ...probability density functions (PDFs). A plethora of photo-z PDF estimation methodologies abound, producing discrepant results with no consensus on a preferred approach. We present the results of a comprehensive experiment comparing 12 photo-z algorithms applied to mock data produced for The Rubin Observatory Legacy Survey of Space and Time Dark Energy Science Collaboration. By supplying perfect prior information, in the form of the complete template library and a representative training set as inputs to each code, we demonstrate the impact of the assumptions underlying each technique on the output photo-z PDFs. In the absence of a notion of true, unbiased photo-z PDFs, we evaluate and interpret multiple metrics of the ensemble properties of the derived photo-z PDFs as well as traditional reductions to photo-z point estimates. We report systematic biases and overall over/underbreadth of the photo-z PDFs of many popular codes, which may indicate avenues for improvement in the algorithms or implementations. Furthermore, we raise attention to the limitations of established metrics for assessing photo-z PDF accuracy; though we identify the conditional density estimate loss as a promising metric of photo-z PDF performance in the case where true redshifts are available but true photo-z PDFs are not, we emphasize the need for science-specific performance metrics.
Contents
Pigs are an attractive animal model to study the progression of cancer because of their anatomical and physiological similarities to human. However, the use of pig models for cancer research ...has been limited by availability of genetically engineered pigs which can recapitulate human cancer progression. Utilizing genome editing technologies such as CRISPR/Cas9 system allows us to generate genetically engineered pigs at a higher efficiency. In this study, specific CRISPR/Cas9 systems were used to target RUNX3, a known tumour suppressor gene, to generate a pig model that can induce gastric cancer in human. First, RUNX3 knockout cell lines carrying genetic modification (monoallelic or biallelic) of RUNX3 were generated by introducing engineered CRISPR/Cas9 system specific to RUNX3 into foetal fibroblast cells. Then, the genetically modified foetal fibroblast cells were used as donor cells for somatic cell nuclear transfer, followed by embryo transfer. We successfully obtained four live RUNX3 knockout piglets from two surrogates. The piglets showed the lack of RUNX3 protein in their internal organ system. Our results demonstrate that the CRISPR/Cas9 system is effective in inducing mutations on a specific locus of genome and the RUNX3 knockout pigs can be useful resources for human cancer research and to develop novel cancer therapies.
Hepatotoxicity with first-line drugs, a major complication of anti-tuberculosis treatment, has not been studied by time-dependent analysis.
Adult patients diagnosed with pulmonary tuberculosis (PTB) ...from 2005 to 2009 were reviewed retrospectively. Hepatotoxicity during anti-tuberculosis treatment was defined by symptomatic elevation of liver transaminases ≥3 times the upper limit of normal, or ≥5 times if asymptomatic. Risk factors for hepatotoxicity were investigated using time-dependent Cox regression analysis.
Of 926 patients identified and followed for 4122.9 person-months (pm), 111 (12.0%) developed hepatotoxicity after a median 38.0 days from start of treatment. Around 3.5% had severe hepatotoxicity. The most common symptoms were general malaise and poor appetite. The incidence rate of hepatotoxicity was 0.59, 0.69 and 3.71/100 pm for isoniazid, rifampicin (RMP) and pyrazinamide (PZA), respectively. Old age, female sex, autoimmune disease, human immunodeficiency virus infection, more days with PZA in the last 8-14 days, and fewer days with RMP in the last 15-21 days before hepatotoxicity were independent risk factors for hepatotoxicity during treatment.
A significant number of adult patients on first-line treatment experience hepatotoxicity. PZA is the most common causative drug. For high-risk patients, careful adjustment of the anti-tuberculosis regimen and regular monitoring of liver transaminases are necessary.
The synthesis, swelling kinetics, and optical diffraction of inverse opal hydrogel sensors (see Figure) are demonstrated. Colloidal crystal templating is used to prepare methacrylate/acrylic acid ...(AA) copolymers that have an interconnected pore structure, allowing facile diffusion and a relatively rapid response. The system shows good mechanical stability and pH‐dependent shifts in optical diffraction regulated by the AA concentration.
The efficacy of heparin-bridging therapy during the initiation of oral anticoagulation therapy (OAC) in non-valvular atrial fibrillation (NVAF) is unclear.
To evaluate the efficacy and the safety of ...heparin-bridging therapy during OAC initiation in NVAF patients.
This study included 5327 consecutive warfarin-naïve NVAF patients who received OAC that was initiated with (n = 1053) or without (n = 4274) heparin bridging at four tertiary hospitals. Stroke and bleeding events within 30 days of OAC were evaluated.
While there was no difference in the incidence of stroke (0.5% vs. 0.3%, P = 0.381), major bleeding rate (0.9% vs. 0.3%, P = 0.004) was higher in heparin-bridged than in non-bridged patients. This trend remained in the propensity score-matched population (stroke 0.5% vs. 0.6%, P = 0.762; major bleeding 0.8% vs. 0.1%, P = 0.019). A high CHA2 DS2 -VASc score was an independent predictor for stroke, whereas bridging therapy had no beneficial effect in preventing stroke regardless of CHADS2 or CHA2 DS2 -VASc scores. The HAS-BLED score had a predictive value for major bleeding (odds ratio 1.80, 95% confidence interval 1.11-2.92, P = 0.018), and heparin-bridging therapy was associated with a higher major bleeding rate (odds ratio 4.44, 95% confidence interval 1.68-11.72, P = 0.003), especially in patients with a HAS-BLED score of ≥ 1.
The heparin-bridging therapy increased bleeding without the benefit of preventing stroke at the initiation of OAC in NVAF. Our data suggest that heparin bridging should not be considered at the initiation of OAC in NVAF patients.
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