Results of a multi-institutional, randomized, non-inferiority, phase III trial of accelerated fractionation versus standard fractionation in radiation therapy for T1-2N0M0 glottic cancer: Japan Clinical Oncology Group Study (JCOG0701).

Background: We assessed the non-inferiority of accelerated fractionation (AF) (2.4 Gy/fraction) compared with standard fractionation (SF) (2 Gy/fraction) regarding progression-free survival (PFS) in patients with T1-2N0M0 glottic cancer (GC). Patients and methods: In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20-80, Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. Patients were randomly assigned to receive either SF of 66-70 Gy (33-35 fractions), or AF of 60-64.8 Gy (25-27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%. Results: Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9% (95% confidence interval [CI] 73.4-85.4) for SF and 81.7% (95% CI 75.4-87.0) for AF (difference 1.8%, 91% CI-5.1% to 8.8%; one-sided P = 0.047 > 0.045). The cumulative incidences of local failure at 3 years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms. Conclusion: Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC. Clinical trials registration: UMIN Clinical Trial Registry, number UMIN000000819.

Dehydroepiandrosterone administration increased trabecular mass and dihydrotestosterone levels in the cancellous region of the tibia in young female rats.

The aim of the present study was to determine whether dehydroepiandrosterone (DHEA) administration affects bone mass and local sex hormone levels in the cancellous region of young female rats. Eleven female rats (6 weeks old) were randomly divided into 2 groups: control rats (CON, n=5) and rats treated with DHEA (DHEA, n=6). DHEA dissolved in sesame oil was administered to the DHEA group intraperitoneally at 20 mg DHEA/kg body weight, and the CON group was treated with vehicle only (sesame oil, 0.5 ml). The rats were treated with DHEA or vehicle for 3 consecutive days, followed by 1 day of no treatment. The experimental period was 8 weeks. According to dual-energy X-ray absorptiometry and high-resolution microcomputed tomography data, the DHEA group exhibited increased trabecular bone mineral density (BMD), bone volume, and tibial thickness compared to the findings in the CON group, whereas no effect was observed on cortical BMD or morphometry. The concentrations of free testosterone and estradiol in the cancellous region of the tibia did not differ between the 2 groups, but the DHT concentration was significantly higher in the DHEA group than in the CON group. These findings suggest that an increase in local DHT levels may stimulate an increase in trabecular bone mass during growth phases in female rats.

Progress in thermal comfort research over the last twenty years.

Climate change and the urgency of decarbonizing the built environment are driving technological innovation in the way we deliver thermal comfort to occupants. These changes, in turn, seem to be setting the directions for contemporary thermal comfort research. This article presents a literature review of major changes, developments, and trends in the field of thermal comfort research over the last 20 years. One of the main paradigm shift was the fundamental conceptual reorientation that has taken place in thermal comfort thinking over the last 20 years; a shift away from the physically based determinism of Fanger's comfort model toward the mainstream and acceptance of the adaptive comfort model. Another noticeable shift has been from the undesirable toward the desirable qualities of air movement. Additionally, sophisticated models covering the physics and physiology of the human body were developed, driven by the continuous challenge to model thermal comfort at the same anatomical resolution and to combine these localized signals into a coherent, global thermal perception. Finally, the demand for ever increasing building energy efficiency is pushing technological innovation in the way we deliver comfortable indoor environments. These trends, in turn, continue setting the directions for contemporary thermal comfort research for the next decades.

Interleukin-10 expression induced by adeno-associated virus vector suppresses proteinuria in Zucker obese rats.

Varying degrees of metabolic abnormalities mediated by chronic inflammation are implicated in the chronic glomerular injuries associated with obesity. Interleukin (IL)-10, a pleiotropic cytokine, exerts anti-inflammatory effects in numerous biological settings. In the present study, we explored the biological benefits of adeno-associated virus (AAV) vector-mediated sustained IL-10 expression against the pathological renal characteristics observed in Zucker fatty rats (ZFRs). We injected an AAV vector, encoding rat IL-10 or enhanced green fluorescent protein (GFP) into male ZFRs at 5 weeks of age. Subsequently, the renal pathophysiological changes were analyzed. Persistent IL-10 expression significantly reduced the urinary protein excretion of ZFRs compared with GFP expression (47.1±11.6 mg per mg·creatinine versus 88.8±30.0 mg per mg·creatinine, P<0.01). The serum levels of IL-10 negatively correlated with the urinary protein in AAV-treated rats (r=-0.78, P<0.01). Renal hypertrophy, increased widths in the glomerular basement membrane, and the lack of uniformity and regularity of the foot process of the visceral glomerular epithelial cells of ZFRs were significantly blunted by IL-10 expression. IL-10 also abrogated the downregulation of glomerular nephrin observed in ZFRs treated with the GFP vector. Our findings provide insights into the potential benefit of the anti-inflammatory effects of IL-10 on the overall management of glomerulopathy induced by the metabolic disorders associated with obesity.

Two cases of renal hypouricemia in which dopamine infusion produced a good recovery from exercise-induced acute kidney injury.

We report 2 cases with a good recovery from acute kidney injury (AKI) due to exercise-induced AKI associated with renal hypouricemia. Case 1 involves a 20-yearold man who had a similar episode 1 year earlier. He complained of nausea, vomiting and loin pain after playing football. On admission, his serum creatinine was 3.27 mg/dl and he was treated with intravenous fluid infusion (2 l/d). His renal function deteriorated and creatinine rose to 9.82 mg/dl. A renal hemodynamic evaluation using duplex Doppler ultrasound showed a high arterial resistance index (RI). After we changed his treatment to intravenous continuous infusion of 2 µg/kg/min dopamine, RI decreased sequentially and creatinine decreased without hemodialysis. A renal biopsy performed 7 days after dopamine infusion showed no changes in glomeruli and tubules, suggesting the absence of acute tubular necrosis, and no uric acid crystals or myoglobin casts in tubules. Case 2 involves a 42-year-old man who complained of loin pain after riding a motorcycle. On admission, his creatinine and creatine phosphokinase (CPK) were 3.93 mg/dl and 59 mU/ml, respectively. His RI was also high and he was treated immediately with an intravenous continuous infusion of 2 µg/kg/min dopamine. RI and creatinine decreased sequentially. Both cases suggest the effectiveness of dopamine infusion for AKI due to renal hypouricemia in which the RI of the renal arteries is high.

Virus activation and immune function during intense training in rugby football players.

Epidemiological studies suggest that highly trained athletes are more susceptible to upper respiratory tract infections (URTI) compared with the general population. Upper respiratory symptoms (URS) often appear as either primary invasion of pathogenic organisms and/or reactivation of latent viruses such as Epstein-Barr virus (EBV). The purpose of this study was to examine the relationship between EBV reactivation and the appearance of URS during intensive training in collegiate rugby football players. We evaluated EBV-DNA expression in saliva and examined the relationship between onset of URS and daily changes in EBV-DNA as well as secretory immunoglobulin A (SIgA) levels among 32 male collegiate rugby football players during a 1-month training camp. The EBV-DNA expression tended to be higher in subjects who exhibited sore throat (p=0.07) and cough (p=0.18) than that of those who had no symptoms, although their differences were not significant. The SIgA level was significantly lower 1 day before the EBV-DNA expression (p<0.05). The number of URS increased along with the EBV-DNA expression and decrease of SIgA levels. These results suggest that the appearance of URS is associated with reactivation of EBV and reduction of SIgA during training.

Abrogation of bronchial eosinophilic inflammation and airway hyperreactivity in signal transducers and activators of transcription (STAT)6-deficient mice.

Signal transducers and activators of transcription 6 (STAT6) is essential for interleukin 4-mediated responses, including class switching to IgE and induction of type 2 T helper cells. To investigate the role of STAT6 in allergic asthma in vivo, we developed a murine model of allergen-induced airway inflammation. Repeated exposure of actively immunized C57BL/6 mice to ovalbumin (OVA) aerosol increased the level of serum IgE, the number of eosinophils in bronchoalveolar lavage (BAL) fluid, and airway reactivity. Histological analysis revealed peribronchial inflammation with pulmonary eosinophilia in OVA-treated mice. In STAT6-deficient (STAT6-/-) C57BL/6 mice treated in the same fashion, there were no eosinophilia in BAL and significantly less peribronchial inflammation than in wild-type mice. Moreover STAT6-/- mice had much less airway reactivity than wild-type mice. These findings suggest that STAT6 plays a crucial role in the pathogenesis of allergen-induced airway inflammation.

First measurement of the b-jet cross section in events with a W boson in pp collisions at square root(s) = 1.96 TeV.

The cross section for jets from b quarks produced with a W boson has been measured in pp collision data from 1.9 fb(-1) of integrated luminosity recorded by the CDF II detector at the Tevatron. The W+b-jets process poses a significant background in measurements of top quark production and prominent searches for the Higgs boson. We measure a b-jet cross section of 2.74+/-0.27(stat)+/-0.42(syst) pb in association with a single flavor of leptonic W boson decay over a limited kinematic phase space. This measured result cannot be accommodated in several available theoretical predictions.

Search for pair production of supersymmetric top quarks in dilepton events from pp collisions at sqrt[s]=1.96 TeV.

We present the results of a search for pair production of the supersymmetric partner of the top quark (the top squark t{1}) decaying to a b quark and a chargino χ{1}{±} with a subsequent χ{1}{±} decay into a neutralino χ{1}{0}, lepton ℓ, and neutrino ν. Using a data sample corresponding to 2.7 fb{-1} of integrated luminosity of pp collisions at sqrt[s]=1.96 TeV collected by the CDF II detector, we reconstruct the mass of top squark candidate events and fit the observed mass spectrum to a combination of standard model processes and t{1}t{1} signal. We find no evidence for t{1}t{1} production and set 95% C.L. limits on the masses of the top squark and the neutralino for several values of the chargino mass and the branching ratio B(χ{1}{±}→χ{1}{0}ℓ{±}ν).

Diagnostic Value of Model-Based Iterative Reconstruction Combined with a Metal Artifact Reduction Algorithm during CT of the Oral Cavity.

BACKGROUND AND PURPOSE: Metal artifacts reduce the quality of CT images and increase the difficulty of interpretation. This study compared the ability of model-based iterative reconstruction and hybrid iterative reconstruction to improve CT image quality in patients with metallic dental artifacts when both techniques were combined with a metal artifact reduction algorithm. MATERIALS AND METHODS: This retrospective clinical study included 40 patients (men, 31; women, 9; mean age, 62.9 ± 12.3 years) with oral and oropharyngeal cancer who had metallic dental fillings or implants and underwent contrast-enhanced ultra-high-resolution CT of the neck. Axial CT images were reconstructed using hybrid iterative reconstruction and model-based iterative reconstruction, and the metal artifact reduction algorithm was applied to all images. Finally, hybrid iterative reconstruction + metal artifact reduction algorithms and model-based iterative reconstruction + metal artifact reduction algorithm data were obtained. In the quantitative analysis, SDs were measured in ROIs over the apex of the tongue (metal artifacts) and nuchal muscle (no metal artifacts) and were used to calculate the metal artifact indexes. In a qualitative analysis, 3 radiologists blinded to the patients' conditions assessed the image-quality scores of metal artifact reduction and structural depictions. RESULTS: Hybrid iterative reconstruction + metal artifact reduction algorithms and model-based iterative reconstruction + metal artifact reduction algorithms yielded significantly different metal artifact indexes of 82.2 and 73.6, respectively (95% CI, 2.6-14.7; P < .01). The latter algorithms resulted in significant reduction in metal artifacts and significantly improved structural depictions(P < .01). CONCLUSIONS: Model-based iterative reconstruction + metal artifact reduction algorithms significantly reduced the artifacts and improved the image quality of structural depictions on neck CT images.

First observation of B(s)(0) --> D(s)(+/-)K(-/+) and measurement of the ratio of branching fractions B(B(s)(0) --> D(s)(+/-)K(-/+)/B(B(s)(0) --> D(s)(+)pi(-)).

A combined mass and particle identification fit is used to make the first observation of the decay B(s)(0) --> D(s)(+/-)K(-/+) and measure the branching fraction of B(s)(0) --> D(s)(+/-)K(-/+) relative to B(s)(0) --> D(s)(+)pi(-). This analysis uses 1.2 fb(-1) integrated luminosity of pp collisions at square root(s) = 1.96 TeV collected with the CDF II detector at the Fermilab Tevatron collider. We observe a B(s)(0) --> D(s)(+/-)K(-/+) signal with a statistical significance of 8.1 sigma and measure B(B(s)(0) --> D(s)(+/-)K(-/+) /B(B(s)(0) --> D(s)(+)pi(-) 0.097+/-0.018(stat) +/- 0.009(syst).

Search for Higgs bosons predicted in two-Higgs-doublet models via decays to tau lepton pairs in 1.96 TeV pp collisions.

We present the results of a search for Higgs bosons predicted in two-Higgs-doublet models, in the case where the Higgs bosons decay to tau lepton pairs, using 1.8 fb(-1) of integrated luminosity of pp collisions recorded by the CDF II experiment at the Fermilab Tevatron. Studying the mass distribution in events where one or both tau leptons decay leptonically, no evidence for a Higgs boson signal is observed. The result is used to infer exclusion limits in the two-dimensional space of tanbeta versus m(A) (the ratio of the vacuum expectation values of the two Higgs doublets and the mass of the pseudoscalar boson, respectively).

Search for the associated production of the standard-model Higgs Boson in the all-hadronic channel.

We report on a search for the standard-model Higgs boson in pp collisions at square root(s) = 1.96 TeV using an integrated luminosity of 2.0 fb(-1). We look for production of the Higgs boson decaying to a pair of bottom quarks in association with a vector boson V (W or Z) decaying to quarks, resulting in a four-jet final state. Two of the jets are required to have secondary vertices consistent with B-hadron decays. We set the first 95% confidence level upper limit on the VH production cross section with V(--> qq/qq')H(--> bb) decay for Higgs boson masses of 100-150 GeV/c2 using data from run II at the Fermilab Tevatron. For m(H) = 120 GeV/c2, we exclude cross sections larger than 38 times the standard-model prediction.

Precision measurement of the X(3872) mass in J/psi pi(+) pi(-) decays.

We present an analysis of the mass of the X(3872) reconstructed via its decay to J/psi pi(+)pi(-) using 2.4 fb(-1) of integrated luminosity from pp collisions at square root(s)=1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. The possible existence of two nearby mass states is investigated. Within the limits of our experimental resolution the data are consistent with a single state, and having no evidence for two states we set upper limits on the mass difference between two hypothetical states for different assumed ratios of contributions to the observed peak. For equal contributions, the 95% confidence level upper limit on the mass difference is 3.6 MeV/c(2). Under the single-state model the X(3872) mass is measured to be 3871.61+/-0.16(stat)+/-0.19(syst) MeV/c(2), which is the most precise determination to date.

Exercise in, and adaptations to a cold environment have no effect on SIgA.

AIM: The authors hypothesized that inconsistent SIgA response to exercise is caused by the different adaptative status of subjects to a cold environment. The purposes of the study were to examine whether moderate-intense exercise in a cold environment decreases SIgA and whether adaptation to a cold environment has any effect on SIgA. METHODS: Young male skaters, short track (N=9) and inline (N=10), participated in this study. All subjects cycled for 60 min at 65% VO(2max) in cold (ambient temperature: 5 +or - 1 degrees Celsius, relative humidity 41 + or - 9%) and thermoneutral (ambient temperature: 21 + or - 1 degrees Celsius, relative humidity 35 + or - 5%) conditions. Saliva samples were collected as follows: before and after 1hour of environmental exposure; immediately, 30-min, 60-min and 120-min after the exercise. RESULTS AND CONCLUSIONS: Salivary SIgA and saliva flow rate decreased after the exercise in both groups only in thermoneutral conditions. The SIgA secretion rate did not decrease after moderate-high intensity exercise in a cold environment, and the SIgA response to exercise was not affected by the different adaptative status of subjects to the cold environment.

Basic properties of ATP-induced myosin head movement in hydrated myosin filaments, studied using the gas environmental chamber.

Although more than 50 years have passed since the monumental discovery of Huxley and Hanson that muscle contraction results from relative sliding between actin and myosin filaments, coupled with ATP hydrolysis, the mechanism underlying the filament sliding still remains to be a mystery. It is generally believed that the myofilament sliding is caused by cyclic attachment-detachment between myosin heads in myosin filaments and myosin-binding sites in actin filaments. Attempts to prove the myosin head movement using techniques of X-ray diffraction and chemical probes attached to myosin heads have failed to obtain clear results because of the asynchronous nature of myosin head movement. Using the gas environmental chamber (EC) attached to an electron microscope, we succeeded in recording myosin head movement in hydrated myosin filaments, coupled with ATP hydrolysis with the following results: (1)In the absence of actin filaments, myosin heads fluctuate around a definite neutral position, so that their time-averaged position remains unchanged; (2) On ATP application, myosin heads bind with ATP to be in the charged-up state, M-ADP-Pi, and perform a recovery stroke in the direction away from the myosin filament central bare zone and stay in the post-recovery stroke position; (3) In the actin-myosin filament mixture, myosin heads form rigor linkages with actin, and bind with applied ATP to be in the charged-up state, M-ADP-Pi, and perform a power stroke in the direction towards the myosin filament bare zone, while releasing ADP and Pi to stay in the post-power stroke position; (4) In both recovery and power strokes, myosin heads in the non charged-up state return to the neutral position. These results indicate that the charged-up myosin heads decide their direction of movement without being guided by actin filaments.

Observation and mass measurement of the baryon Xib-.

We report the observation and measurement of the mass of the bottom, strange baryon Xi(b)- through the decay chain Xi(b)- -->J/psiXi-, where J/psi-->mu+mu-, Xi- -->Lambdapi-, and Lambda-->ppi-. A signal is observed whose probability of arising from a background fluctuation is 6.6 x 10(-15), or 7.7 Gaussian standard deviations. The Xi(b)- mass is measured to be 5792.9+/-2.5(stat) +/- 1.7(syst) MeV/c2.

[Isolated intracavitary metastatic hepatocellular carcinoma of the right atrium without inferior vena cava involvement; report of a case].

A 63-year-old female had been treated for liver cirrhosis and hepatocellular carcinoma (HCC) since 3 years before. She developed symptoms of dyspnea and echocardiography revealed a large tumor in the right atrium. The stalk of tumor was attached to the intraatrial septum just above the tricuspid valve and the tumor was floating between the right atrium and the right ventricle according to cardiac rhythm. The size of tumor was 30 x 15 mm in diameter. She was admitted to our hospital for emergency operation. She was operated for cardiac tumor under cardiopulmonary bypass successfully and the postoperative course was uneventful. But the pathology reported direct intracavitary metastasis of HCC without intravascular involvement. She was discharged on the 7th postoperative day for the treatment of HCC.

[Perioperative coronary spasm in the modified Bentall's operation for localized dissecting aneurysm of Valsalva sinuses].

A 55-year-old man had suffered from chest oppression while asleep for 1 to 2 years. Moderate aortic regurgitation and aneurysm of Valsalva sinuses were revealed by echocardiography. It was diagnosed as chronic localized dissecting aneurysm of Valsalva sinuses during the operation, and modified Bentall's operation was performed. The patient was extubated 2 hours after the operation. ST segment depression in leads I, aV(L) and V3-V6, and elevation in leads III and aV(R) suddenly occurred 5 hours after the operation. However, hemodynamics was very stable, and he complained of no chest pain. Cardiac asystole was detected 7 hours after the operation, and percutaneous cardiopulmonary support as well as intraaortic balloon pumping (IABP) was immediately started. Emergency coronary angiography revealed acute myocardial infarction due to severe coronary spasm in the left coronary artery. The patient expired on the 3rd postoperative day.

[The saccular coronary aneurysm associated with coronary artery to pulmonary artery fistulae].

Coronary artery fistulae are relatively rare congenital anomalies. Those associated with saccular coronary artery aneurysms are even rarer. Including the current case, only 65 such cases have been reported in Japan. A 62-year-old female was admitted to our hospital for evaluation of abnormal shadow on the chest X-ray. The enhanced chest computed tomography (CT) scan demonstrated a giant saccular coronary aneurysm on the left side of the pulmonary artery. Multi-detector row CT (MDCT) scan demonstrated the coronary artery aneurysm was connected to the left anterior descending artery. Coronary angiography revealed 2 aneurysms with bilateral coronary artery to pulmonary artery fistulae. The patient underwent aneurysmectomy and ligation of fistulae under cardiopulomonary bypass. The postoperative course was uneventful and postoperative coronary angiography revealed complete resection of the aneurysms and only slight blood flow through the fistulae. She was discharged on the 10th postoperative day.