This study aimed to determine the clinical benefit of neoadjuvant methotrexate, doxorubicin, vinblastine, and cisplatin (MVAC) in patients with muscle-invasive bladder cancer (MIBC) treated with ...radical cystectomy.
Patients with MIBC (T2-4aN0M0) were randomised to receive two cycles of neoadjuvant MVAC followed by radical cystectomy (NAC arm) or radical cystectomy alone (RC arm). The primary end point was overall survival (OS). Secondary end points were progression-free survival, surgery-related complications, adverse events during chemotherapy, proportion with no residual tumour in the cystectomy specimens, and quality of life. To detect an improvement in 5-year OS from 45% in the RC arm to 57% in the NAC arm with 80% power, 176 events were required per arm.
Patients (N = 130) were randomly assigned to the RC arm (N = 66) and the NAC arm (N = 64). The patient registration was terminated before reaching the initially planned number of patients because of slow accrual. At the second interim analysis just after the early stoppage of patient accrual, the Data and Safety Monitoring Committee recommended early publication of the results because the trial did not have enough power to draw a confirmatory conclusion. OS of the NAC arm was better than that of the RC arm, although the difference was not statistically significant hazard ratio 0.65, multiplicity adjusted 99.99% confidence interval 0.19–2.18, one-sided P = 0.07. In the NAC arm and the RC arm, 34% and 9% of the patients had pT0, respectively (P < 0.01). In subgroup analyses, OS in almost all subgroups was in favour of NAC.
This trial showed a significantly increased pT0 proportion and favourable OS of patients who received neoadjuvant MVAC. NAC with MVAC can still be considered promising as a standard treatment.
C000000093.
This study found several in situ fossil shells of the boring bivalve Penitella gabbii exposed in mudstone at an elevation of 1.05–1.35 m above mean sea level in a wave-cut platform at Cape Omaezaki, ...Shizuoka, central Japan. This region faces the Nankai Trough where great earthquakes (M ~8) occur with a recurrence interval of 90–200 years. Based on the upper limit of living P. gabbii (−0.8 m above mean sea level) and geodetic data, the total uplift of shells since the time of their active is estimated to be up to 2.5 m. Using 14C dates from the uplifted terrace deposits around the study area and shell fossils, we propose that the emerged fossils provide new evidence for the pairing of the 1361 CE Shohei (Koan)–Tokai earthquake (rupture of Suruga Trough and the eastern half of the Nankai Trough) with the 1361 CE Shohei (Koan)–Nankai earthquake (rupture of the western half of the Nankai Trough).
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The quality of life and safeness of the present and future generations are strongly intertwined with the availability of energy sources and the sustainability of the energy infrastructure. Energy ...consumption in developed countries grows at a rate of approximately 1% per year, and that of developing countries, 5% per year (Muneer et al., 2005 1). Present reserves of oil and natural gas can only cover consumption at this rate for the next 50 years in the case of oil, and for the next 70 years in the case of natural gas. Therefore, one of the fundamental priorities for a country such as Algeria is to use several renewable energies (RE) sources and environmentally friendly energy conversion technologies. Algeria is endowed with large reserves of energy sources, mainly hydrocarbons and a considerable potential for the utilisation of RE sources especially with respect to solar energy. Algeria has the potential to be one of the major contributors in solar energy and become a role model to other countries in the world. RE are now one of the major elements of Algeria's energy policy and in view of boosting the national effort in terms of RE beyond 2011, Algeria has developed a national programme for the period 2011–2030 to promote concrete actions in the fields of energy efficiency and RE in line with the approach adopted by the government on February 3, 2011. Besides, it confirms Algerian's ambition to become an international hub for industrial and energy production and exportation in the solar sector. With this in mind, along with the environmental responsibility issues, public awareness gradually increased over the last seven years and alternative energy resources have become a new area of interest. As a tangible target, the Ministry of Energy and Mines (MEM) strategic plan aims to reach a 40% share of RE (mainly solar) in electric energy production by 2030. The various future projects are all factors that will undoubtedly give Algeria an important role in the implementation of RE technology in North Africa, the capacity for providing sustainable supply of cost-effective electricity from RE sources for the needs of the population, and the possibility of even exporting 10,000MW to neighbouring and European market. This paper provides a detailed analysis of the existing renewable energy sector and a forecast for demand growth, additional capacity, investment requirements and Algeria's ambitious objectives of use of RE and environment protection. The paper also discusses the current energy scenario and explores the alternative energy like solar and wind to ensure energy security supply, reliability, greater efficiency in energy conversion, transmission and utilisation. Particular attention is paid to Algeria's global and sustainable solutions of the environmental challenges and the problems of conservation of fossil energy resources under the clean development mechanism (CDM) structure. The report also provides a detailed analysis of the existing renewable energy sector and a forecast for demand growth, additional capacity, and investment requirements
Background
Shifting enables flexible switch between tasks or mental sets. It is a component of the executive function that plays critical roles in human behaviour control. However, shifting ability ...in individuals with intellectual disability (ID) has not been well clarified because of the use of intellectually demanding tasks in previous studies. The present study invented a novel shifting task with minimal intellectual demands and aimed to clarify the characteristics of shifting in adolescents with ID.
Methods
Adolescents with ID (n = 21) and chronological‐age‐matched (n = 10) and mental‐age‐matched controls (n = 33) performed a novel shifting task with simple rule switching (i.e. change in direction). Analyses focused on the switch cost or the increase in the reaction time associated with rule switching.
Results
Two subtypes of adolescents with ID were found with respect to the switch cost: one that lacks it and another with an increased switch cost. The lack of a switch cost was unique to the subgroup adolescents with ID and was not indicated in the control group.
Conclusions
The present study indicated that shifting in adolescents with ID does not depend solely on their intellectual function and is highly heterogeneous. This finding further implies that executive functions, including shifting, must be evaluated separately from their intellectual functions.
Abstract Recent studies of the freshwater planarian Dugesia japonica have revealed fundamental mechanisms and unique aspects of neuroscience and neuroregeneration. Here, we identified the gene for ...planarian choline acetyltransferase ( Djchat ), which is essential for acetylcholine (ACh) biosynthesis. Immunofluorescence studies using anti- Dugesia japonica ChAT (DjChAT) antibody revealed that cholinergic neurons are widely distributed in the planarian nervous system, including the brain, ventral nerve cords, optic nerves, and pharyngeal nerve plexus. In order to investigate the function of cholinergic neurons in planarians, we used both pharmacological and RNA interference (RNAi) approaches. Administration of physostigmine (an acetylcholinesterase inhibitor) clearly elevated the amount of ACh, and then induced sudden muscle contraction behavior in a concentration-dependent manner. In addition, we found that pretreatment with tubocurarine (a muscle nicotinic ACh receptor antagonist) or atropine (a non-selective muscarinic ACh receptor antagonist), but not pretreatment with mecamylamine (a neural nicotinic ACh receptor antagonist), significantly extended the latency time for physostigmine-induced contraction behavior, suggesting that muscle nicotinic ACh receptors and muscarinic ACh receptors contribute to physostigmine-induced contraction behavior. We also confirmed that ACh biosynthesis ability and DjChAT-immunoreactivity were eliminated in Djchat(RNAi) planarians. Moreover, the decrease of the level of ACh induced by Djchat(RNAi) caused extension of the latency time for contraction behavior. Our findings support the possibility that the cholinergic functions of planarians are similar to those of vertebrates, suggesting that planarians are simple but useful model organisms for getting insight into the cholinergic nervous system in higher animals.
The authors develop two-dimensional and three-dimensional simulation codes of the transient response of the temperature distribution in the lithium ion secondary battery during a discharge cycle. At ...first, a two-dimensional simulation code for a cylindrical battery is developed, and the simulation results for a commercially available small size battery are compared with the corresponding experimental results. The simulation results of the transient temperature and voltage variations coincide very well with the experimental results. The simulation result of the temperature difference between the center of the battery body and the center of the battery side is also in reasonable agreement with the experimental result. Next, the authors develop a three-dimensional simulation code and perform numerical simulations for three large size prismatic batteries with the same capacity and different cross sectional shapes. It is made clear that selecting the battery with the laminated cross section has a remarkable effect on the suppression of the temperature rise in comparison with the battery with square cross section, whereas the effect of the lamination on the suppression of the temperature unevenness is unexpectedly small. These results indicate the accuracy and usefulness of the developed simulation codes.
We reviewed epidemiologic studies of cigarette smoking and the risk of cervical cancer among Japanese women, and we conclude that cigarette smoking convincingly increases the risk of cervical cancer.
...Abstract
Background
There is a body of evidence to suggest that cigarette smoking increases the risk of cervical cancer in women, but no study has examined the magnitude of the association in Japanese women. Here, we evaluated the association between cigarette smoking and the risk of cervical cancer in Japanese women based on a systematic review of epidemiological evidence.
Methods
Original data were obtained from a MEDLINE search using PubMed or from a search of the ‘Ichushi’ database, as well as by a manual search. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as evaluated previously by the International Agency for Research on Cancer. Meta-analysis of associations was also conducted to obtain a summarized overview of the data.
Results
We identified two cohort studies and three case-control studies. All five studies had indicated strong positive associations between cigarette smoking and the risk of cervical cancer. Our summary estimate indicated that the relative risk (RR) for individuals who had ever-smoked relative to never-smokers was 2.03 (95% confidence interval: 1.49–2.57). Four studies had also demonstrated dose–response relationships between cigarette smoking and the risk of cervical cancer.
Conclusion
We conclude that there is convincing evidence that cigarette smoking increases the risk of cervical cancer among Japanese women.
Signals through Kit receptor tyrosine kinase are essential for development of erythrocytes, melanocytes, germ cells, mast cells and interstitial cells of Cajal (ICCs). Mice and rats with a double ...gene dose of loss-of-function mutations of Kit show depletion of these cells. Although human homozygotes with loss-of-function mutations of Kit have not been reported, gain-of-function mutations of Kit result in development of tumors from mast cells, germ cells and ICCs in humans. The ICC tumors are called gastrointestinal stromal tumors (GISTs), and GISTs are a good target for the Kit inhibitor imatinib mesylate. The interrelationship between the type of Kit gain-of-function mutations and the therapeutic effect of imatinib mesylate has been well characterized in GISTs. Kit is interesting from both a biological and clinical view-point.
Japan is still a medium-burden tuberculosis (TB) country. We aimed to examine trends in newly notified active TB incidence and TB-related mortality in the last two decades in Japan. This is a ...population-based study using Japanese Vital Statistics and Japan Tuberculosis Surveillance from 1997 to 2016. We determined active TB incidence and mortality rates (per 100 000 population) by sex, age and disease categories. Joinpoint regression was applied to calculate the annual percentage change (APC) in age-adjusted mortality rates and to identify the years showing significant trend changes. Crude and age-adjusted incidence rates reduced from 33.9 to 13.9 and 37.3 to 11.3 per 100 000 population, respectively. Also, crude and age-adjusted mortality rates reduced from 2.2 to 1.5 and 2.8 to 1.0 per 100 000 population, respectively. Average APC in the incidence and mortality rates showed significant decline both in men (-6.2% and -5.4%, respectively) and women (-5.7% and -4.6%, respectively). Age-specific analysis demonstrated decreases in incidence and mortality rates for every age category, except for the incidence trend in the younger population. Although trends in active TB incidence and mortality rates in Japan have favourably decreased, the rate of decline is far from achieving TB elimination by 2035.
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