MgO barrier-perpendicular magnetic tunnel junctions with CoFe/Pd multilayers and ferromagnetic insertion layers

The authors studied an effect of ferromagnetic (Co20Fe60B20 or Fe) layer insertion on tunnel magnetoresistance (TMR) properties of MgO-barrier magnetic tunnel junctions (MTJs) with CoFe/Pd multilayer electrodes. TMR ratio in MTJs with CoFeB/MgO/Fe stack reached 67% at an-nealing temperature (Ta) of 200 degree C and then decreased rapidly at Ta over 250 degree C. The degradation of the TMR ratio may be related to crystallization of CoFe(B) into fcc(111) or bcc(011) texture result-ing from diffusion of B into Pd layers. MTJs which were in-situ annealed at 350oC just after depo-siting bottom CoFe/Pd multilayer showed TMR ratio of 78% by post annealing at Ta =200 degree C.Comment: 12 pages, 4 figure

Gamma-Ray Spectroscopy of Λ16^{16}_\LambdaO and Λ15^{15}_\LambdaN Hypernuclei via the 16^{16}O(K−,π−)(K^-, \pi^-) reaction

he bound-state level structures of the $^{16}_{\Lambda}$O and $^{15}_{\Lambda}$N hypernuclei were studied by $\gamma$-ray spectroscopy using a germanium detector array (Hyperball) via the $^{16}$O ($K^-, \pi^- \gamma$) reaction. A level scheme for $^{16}_{\Lambda}$O was determined from the observation of three $\gamma$-ray transitions from the doublet of states ($2^-$,$1^-$) at $\sim 6.7$ MeV to the ground-state doublet ($1^-$,$0^-$). The $^{15}_{\Lambda}$N hypernuclei were produced via proton emission from unbound states in $^{16}_{\Lambda}$O . Three $\gamma$ -rays were observed and the lifetime of the $1/2^+;1$ state in $^{15}_{\Lambda}$N was measured by the Doppler shift attenuation method. By comparing the experimental results with shell-model calculations, the spin-dependence of the $\Lambda N$ interaction is discussed. In particular, the measured $^{16}_{\Lambda}$O ground-state doublet spacing of 26.4 $\pm$ 1.6 $\pm$ 0.5 keV determines a small but nonzero strength of the $\Lambda N$ tensor interaction.Comment: 22 pages, 17 figure

Photo-production of neutral kaons on 12C in the threshold region

Kaon photo-production process on $^{12}$C has been studied by measuring neutral kaons in a photon energy range of 0.8$-$1.1 GeV. Neutral kaons were identified by the invariant mass constructed from two charged pions emitted in the $K^{0}_{S}\to\pi^{+}\pi^{-}$ decay channel. The differential cross sections as well as the integrated ones in the threshold photon energy region were obtained. The obtained momentum spectra were compared with a Spectator model calculation using elementary amplitudes of kaon photo-production given by recent isobar models. Present result provides, for the first time, the information on $n(\gamma,K^{0})\Lambda$ reaction which is expected to play an important role to construct models for strangeness production by the electromagnetic interaction. Experimental results show that cross section of $^{12}{\rm C}(\gamma,K^0)$ is of the same order to that of $^{12}{\rm C}(\gamma,K^+)$ and suggest that slightly backward $K^0$ angular distribution is favored in the $\gamma n\to K^0\Lambda$ process.Comment: 6 pages, 8 figure

Premenopausal cardiovascular disease and age at natural menopause: a pooled analysis of over 170,000 women

Early menopause is associated with an increased risk of subsequent cardiovascular disease (CVD). Few studies have investigated the converse. We examined whether premenopausal CVD events are associated with early age at menopause. We pooled the individual data of 177,131 women from nine studies. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRR) and 95% confidence intervals (CI) for the associations between age at onset of premenopausal CVD events-including coronary heart disease (CHD) and stroke-and age at natural menopause. Altogether 1561 (0.9%) premenopausal participants reported CVD events (including 1130 CHD and 469 stroke) at a mean age of 41.3 years. Compared with women without any premenopausal CVD events, women who experienced a first CVD event before age 35 years had a twofold risk of menopause before age 45 years (early menopause); adjusted RRR (95% CI) of 1.92 (1.17, 3.14) for any CVD, 1.86 (1.01, 3.43) for CHD and 2.17 (1.43, 3.30) for stroke. Women who experienced a first premenopausal CVD event after age 40 years underwent a natural menopause at the expected age (around 51 years). These associations were robust to adjustment for smoking status, BMI, educational level, race/ethnicity, age at menarche, parity, hypertension and family history of CVD. For premenopausal women, a first CVD event before age 35 years is associated with a doubling of the risk of an early menopause, while a first CVD event occurred after 35 years indicates a normal menopause at around 51 years. Shared genetic and environmental factors (such as smoking), as well as compromised vasculature following CVD events, may contribute to this outcome

Clinical efficacy and safety of monthly oral ibandronate 100 mg versus monthly intravenous ibandronate 1 mg in Japanese patients with primary osteoporosis

Summary: The MOVEST study evaluated the efficacy and safety of monthly oral ibandronate versus licensed monthly IV ibandronate in Japanese osteoporotic patients. Relative BMD gains after 12 months were 5.22 % oral and 5.34 % IV, showing non-inferiority of oral to IV ibandronate (primary endpoint). No new safety concerns were identified. Introduction: The randomized, phase 3, double-blind MOVEST (Monthly Oral VErsus intravenouS ibandronaTe) study evaluated the efficacy and safety of monthly oral ibandronate versus the licensed monthly intravenous (IV) ibandronate regimen in Japanese patients with osteoporosis. Methods: Ambulatory patients aged ?55 years with primary osteoporosis were randomized to receive oral ibandronate 100 mg/month plus monthly IV placebo, or IV ibandronate 1 mg/month plus monthly oral placebo. The primary endpoint was non-inferiority of oral versus IV ibandronate with respect to bone mineral density (BMD) gains at the lumbar spine after 12 months of treatment. Results: Four hundred twenty-two patients were enrolled with 372 patients in the per-protocol set (183 and 189 in the oral and IV ibandronate groups, respectively). The relative change from baseline in lumbar spine BMD values for the oral and IV ibandronate groups, respectively, was 5.22 % (95 % confidence interval [CI] 4.65, 5.80) and 5.34 % (95 % CI 4.78, 5.90). The least squares mean difference between the two groups was ?0.23 % (95 % CI ?0.97, 0.51), showing non-inferiority of oral ibandronate to IV ibandronate (non-inferiority limit = ?1.60). Changes in BMD values at other sites, and bone turnover marker levels in the oral ibandronate group, were comparable with those of the IV group. The safety profile was similar to that previously demonstrated; no new safety concerns were identified. Conclusions: This study demonstrated the non-inferiority of oral ibandronate 100 mg/month to IV ibandronate 1 mg/month (licensed dose in Japan) in increasing lumbar spine BMD in Japanese patients with primary osteoporosis

Need for enforcement of ethicolegal education – an analysis of the survey of postgraduate clinical trainees

BACKGROUND: The number of medical lawsuits in Japan was between 14 and 21 each year before 1998, but increased to 24 to 35 per year after 1999. There were 210 lawsuits during this 10-year period. There is a need for skills and knowledge related to ethics, which is as fundamental to the practice of medicine as basic sciences or clinical skills. in Japan education in ethics is relatively rare and its importance is not yet recognized. Establishing ethics education using legal precedents, which has already been achieved in Western countries, will be a very important issue in Japan. In the present study, a questionnaire survey was conducted among graduate intern doctors, in order to investigate whether ethics education using precedents might have a positive effect in Japan. METHODS: In 2002, a questionnaire survey entitled Physicians' Clinical Ethics was carried out in a compulsory orientation lecture given to trainees before they started clinical practice in our hospital. The attendees at this lecture were trainees who came from colleges in various districts of Japan. During the lecture, 102 questionnaires were distributed, completed by attendees and collected. The recovery rate was 100%. The questionnaire consisted of 22 questions (in three categories), of which 20 were answered by multiple choices, and the other two were answered by description. The time required to complete the questionnaire was about 10 minutes. RESULTS: The recovered questionnaires were analyzed using statistical analysis software (SPSS for Windows, Release 10.07J-1/June/2000), in addition to simple statistical analysis. answers using multiple choices for the 20 questions in the questionnaire were input into SPSS. The principal component analysis was performed for each question. As a result, the item that came to the fore was "legal precedent". Since many intern doctors were interested in understanding laws and precedents, learning about ethical considerations through education using precedents might better meet with their needs and interests. CONCLUSION: We applied a new method in which the results of principal component analysis and frequencies of answers to other questions were combined. From this we deduced that the precedent education used in Western countries was useful to help doctors acquire ethical sensitivity and was not against their will. A relationship was found between reading precedents and the influence of lawsuits, and it was thought that student participation-type precedent education would be useful for doctors in order to acquire ethical sensitivity

Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies.

BackgroundCigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause.Methods and findingsA total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (ConclusionsThe probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause

Increased Liver Uptake and Reduced Hepatic Stellate Cell Activation with a Cell-Specific Conjugate of the Rho-kinase Inhibitor Y27632

Rho-kinase regulates activation of hepatic stellate cells (HSC) during liver fibrosis, but the ubiquitous presence of this kinase may hinder examination of its exact role and the therapeutic use of inhibitors. We therefore coupled the Rho-kinase inhibitor Y27632 to a drug carrier that binds the mannose-6-phosphate insulin-like growth factor II (M6P/IGFII)-receptor which is upregulated on activated HSC. Y27632 was coupled to mannose-6-phosphate human serum albumin (M6PHSA), and in vitro experiments were performed on primary rat HSC. Biodistribution and effect studies were performed in an acute CCl(4) model in mice. Y27-conjugate remained stable in serum, while drug was efficiently released in liver homogenates. Receptor-blocking studies revealed that it was specifically taken up through the M6P/IGFII-receptor on fibroblasts, and it inhibited expression of fibrotic markers in activated HSC. In vivo, liver drug levels were significantly higher after injection of Y27-conjugate as compared to Y27632, and the conjugate accumulated specifically in HSC. After acute CCl(4)-induced liver injury, Y27-conjugate reduced the local activation of HSC, whereas an equimolar dose of free drug did not. We conclude that specific targeting of a Rho-kinase inhibitor to HSC leads to enhanced accumulation of the drug in HSC, reducing early fibrogenesis in the liver