bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binding and safety profile of novel benzoxazole derivative for in vivo imaging of amyloid deposits in Alzheimer's disease
Authors: Okamura Nobuyuki , Furumoto Shozo , Funaki Yoshihito , Suemoto Takahiro , Kato Motohisa , Ishikawa Yoichi , Ito Satoshi , Akatsu Hiroyasu , Yamamoto Takayuki , Sawada Tohru , Arai Hiroyuki , Kudo Yukitsuka , Yanai Kazuhiko 
Published: September 2010

Background:  In vivo detection of amyloid deposits in the brain is potentially useful for early diagnosis of Alzheimer's disease (AD) and tracking the efficacy of anti‐amyloid therapy.Methods:  To develop an amyloid‐binding agent for positron emission tomography, we screened over 2600 compounds.Results:  We found benzoxazole derivatives as candidate compounds for in vivo amyloid imaging probes. One of these agents, 2‐(2‐[2‐dimethylaminothiazol‐5‐yl]ethenyl)‐6‐(2‐[fluoro]ethoxy)benzoxazole (BF‐227), displays high binding affinity to Aβ fibrils. BF‐227 binding increased linearly with increasing Aβ fibril formation. In temporal and hippocampal AD brain sections, BF‐227 selectively bound to amyloid plaques. In contrast, no staining was evident in the cerebellum. Compared with the previously reported compound BF‐168, 18F‐labeled BF‐227 displayed selective in vivo labeling of amyloid fibrils and rapid washout from white matter areas in an Aβ‐injected rat model. An acute and subacute toxicity study of BF‐227 indicated sufficient safety for clinical use as a positron emission tomography probe.Conclusions:  These findings suggest that BF‐227 is feasible as an in vivo imaging probe of amyloid deposits in AD patients.
Association of carotid atherosclerosis with genetic polymorphisms of the klotho gene in patients with hypertension
Authors: Oguro Ryosuke , Kamide Kei , Kokubo Yoshihiro , Shimaoka Izumi , Congrains Ada , Horio Takeshi , Hanada Hironori , Ohishi Mitsuru , Katsuya Tomohiro , Okamura Tomonori , Miyata Toshiyuki , Kawano Yuhei , Rakugi Hiromi 
Published: September 2010

Aim:  Previous studies suggest that klotho gene polymorphisms may be associated with atherosclerosis, but did not assess the relationship between klotho gene polymorphisms and atherosclerosis parameters such as carotid artery intima‐media thickness (IMT). Here, we studied whether klotho single nucleotide polymorphisms (SNP) were associated with carotid atherosclerosis.Methods:  All subjects were Japanese. Eight‐hundred and fifty‐three patients with hypertension (465 men and 388 women) in the outpatient clinic and 1783 subjects from the general population (821 men and 962 women) attending health check‐ups were analyzed in the present study. We measured mean IMT of the common carotid artery to evaluate carotid atherosclerosis. Four single nucleotide polymorphisms (SNP) (rs7323281; intron1, rs5644481; exon4, rs3752472; exon3, rs650439; intron4) of klotho were selected as representative SNP in haplotype blocks.Results:  Multivariate logistic regression analysis adjusted by confounding factors showed a significant association of rs650439 with carotid atherosclerosis in hypertensive patients (TT vs TA vs AA, P < 0.01; TT + TA vs AA, P < 0.01). By ancova considering confounding factors, rs650439 was also significantly associated with mean IMT (TT + TA vs AA, P = 0.04) in the hypertensive population. However, there was no significant association between klotho SNP and carotid IMT in the general population. Compared to the general population, the subject group with hypertensive patients clearly had more atherosclerosis risk factors.Conclusion:  Only in hypertensive patients was klotho rs650439 strongly associated with mean IMT thickening of the common carotid artery. Therefore, klotho SNP (rs650439) may influence on the progression of carotid atherosclerosis in patients with hypertension. Geriatr Gerontol Int 2010; 10: 311–318.
Alternative items for identifying hierarchical levels of physical disability by using physical performance tests in women aged 75 years and older
Authors: Kim Mi‐Ji , Yabushita Noriko , Kim Maeng‐Kyu , Matsuo Tomoaki , Okuno Junko , Tanaka Kiyoji 
Published: September 2010

Aim:  To identify individuals at hierarchical levels of physical disability by using physical performance tests and to determine threshold values for the discriminating of levels of physical disability in women aged 75 years or older.Methods:  A cross‐sectional observational study was conducted on 306 community‐dwelling women aged 75 years or order (range, 75–99 years). Physical disability was categorized into no disability, mobility disability and activities of daily living (ADL) disability, by evaluating selected ADL and mobility‐related functional tasks. Physical function tests comprised nine items (such as strength, balance, mobility and walking ability). To assess the observed threshold values, receiver–operator curves were prepared for all the scales.Results:  The results revealed significant differences among all the pairwise group comparisons in all the performance tests, except in the one‐legged stance, tandem stance and tandem walk tests. The individuals with ADL disability were unable to perform the one‐legged stance (28.9%), tandem stance (32.5%), functional reach (19.3%), tandem walk (61.4%), alternate step (53.0%) and 5‐chair sit‐to‐stand (31.3%) tests. The observed thresholds for discriminating between the no disability and mobility disability groups and between the mobility disability and ADL disability groups were as follows: timed Up & Go test, 8.5 s and 12.7 s; usual gait speed, 1.05 m/s and 0.79 m/s; and grip strength, 19.5 kg and 16.3 kg, respectively.Conclusion:  Tests for balance and lower extremity strength can be used together to identify or monitor the characteristics of the hierarchical levels of physical disability in women aged 75 years or older. Geriatr Gerontol Int 2010; 10: 302–310.
Final safety and efficacy analysis of the specific endothelin A receptor antagonist zibotentan (ZD4054) in patients with metastatic castration‐resistant prostate cancer and bone metastases who were pain‐free or mildly symptomatic for pain: a double‐blind, placebo‐controlled, randomized Phase II trial
Authors: James Nicholas D. , Caty Armelle , Payne Heather , Borre Michael , Zonnenberg Bernard A. , Beuzeboc Philippe , McIntosh Stuart , Morris Thomas , Phung De , Dawson Nancy A. 
Published: September 2010

Study Type – Therapy (RCT) Level of Evidence 1bOBJECTIVESTo report the final analysis of a Phase II trial, which investigated the safety and efficacy of the specific endothelin A receptor antagonist zibotentan (AstraZeneca, Macclesfield, UK) in patients with metastatic castration‐resistant prostate cancer (CRPC).PATIENTS AND METHODSPatients with CRPC and bone metastases who were pain free or mildly symptomatic for pain were randomized to receive once‐daily oral tablets of zibotentan 10 mg, 15 mg or placebo. The primary endpoint was the time to progression and secondary endpoints included overall survival, change in the number of bone metastases, and safety.RESULTSIn total, 312 patients were randomized (placebo, n= 107; zibotentan 10 mg, n= 107; zibotentan 15 mg, n= 98). The median duration of study treatment and median follow‐up time were 4 and 22 months, respectively. At the final analysis, there were no statistical differences of the primary outcome of time to progression between treatment groups, although an improvement in overall survival was observed in the zibotentan groups compared to placebo. Consistent with the previous analyses for overall survival, hazard ratios (HRs) of less than one were sustained for both zibotentan 15 mg (HR, 0.76; 80% CI, 0.61–0.94; P= 0.103) and 10 mg (HR, 0.83; 80% CI, 0.67–1.02; P= 0.254). The most commonly reported adverse events considered to be related to zibotentan treatment were peripheral oedema, headache and nasal congestion.CONCLUSIONSThe results obtained in the present study support endothelin A receptor antagonism as an approach for treating patients with CRPC. To confirm the survival signal observed in the present study, zibotentan is being investigated further in the ENdoTHelin A USE (ENTHUSE) Phase III clinical trial programme.
Controversial technology: the Chunnel and the laparoscopic retroperitoneal lymph node dissection (RPLND)
Authors: Schwartz Michael J. , Kavoussi Louis R. 
Published: September 2010

• Laparoscopic retroperitoneal lymph node dissection (L‐RPLND) was first introduced in 1992, initially as a staging procedure.• With advances in instrumentation and laparoscopic techniques, as well as improved understanding of laparoscopic anatomy, L‐RPLND has developed to duplicate open RPLND.• Unlike the relatively rapid adoption of laparoscopy for other applications including nephrectomy and prostatectomy, L‐RPLND has been slow to be universally accepted.• The limited numbers of patients requiring RPLND and technical challenges in performing the dissection have undoubtedly contributed to its delayed reception.• This review will present available data on this technique and discuss issues potentially inhibiting acceptance by traditional surgeons.
Effect of RBP4 gene variants on circulating RBP4 concentration and Type 2 diabetes in a Chinese population
Authors: Hu C. , Jia W. , Zhang R. , Wang C. , Lu J. , Wu H. , Fang Q. , Ma X. , Xiang K. 
Published: September 2010

AbstractAims  Retinol binding protein 4 (RBP4) is a newly discovered adipokine, which plays a role in insulin resistance and obesity. The aim of this study was to determine the relationship between genetic variants of the RBP4 gene, circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism in the Chinese population.Methods  We sequenced exons and the putative promoter region to identify single nucleotide polymorphisms (SNPs) in the RBP4 gene in 32 Chinese subjects. Additional SNPs were selected from a public database to increase marker density. Taking account of the pairwise linkage disequilibrium and minor allele frequencies, a subset of SNPs was further genotyped in 255 Type 2 diabetic patients and 372 normal control subjects. Circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism were measured.Results  Ten SNPs were identified and five were further genotyped in the full sample. No individual SNP was significantly associated with Type 2 diabetes, but a rare haplotype CAA formed by +5388 C>T, +8201 T>A and +8204 T>A was more frequent in diabetic patients (P = 0.0343, empirical P = 0.0659 on 10 000 permutations). In both groups, non‐coding SNPs were associated with circulating RBP4 concentrations (P < 0.05). In the normal control subjects, the SNP +5388 C>T was associated with serum C‐peptide levels both fasting and 2 h after an oral glucose tolerance test (P = 0.0162 and P = 0.0075, respectively).Conclusion  Our findings suggest that genetic variants in the RBP4 gene may be associated with circulating RBP4 concentration and phenotypes related to glucose metabolism.
Acute hyperglycaemia disturbs cardiac repolarization in Type 1 diabetes
Authors: Gordin D. , Forsblom C. , Rönnback M. , Groop P.‐H. 
Published: September 2010

AbstractAims  Patients with Type 1 diabetes have an increased risk of cardiovascular mortality. Notably, a prolonged heart rate adjusted QT interval (QTc) is a predictor of sudden cardiovascular death. Therefore, the objectives of this study were to investigate whether acute hyperglycaemia affects the QTc duration and the QTc dispersion in patients with Type 1 diabetes and in healthy volunteers.Methods  Acute hyperglycaemia (15 mmol/l) for 120 min was induced in 35 males (22 men with Type 1 diabetes and 13 age‐matched non‐diabetic volunteers). All participants were non‐smokers without any diabetic complications. Electrocardiogram recordings were performed at normoglycaemia and at 0, 60 and 120 min of hyperglycaemia.Results  Compared with normoglycaemia, acute hyperglycaemia increased the QTc interval in both patients with Type 1 diabetes (390 ± 6 vs. 415 ± 5 ms, P < 0.001) and in healthy volunteers (378 ± 5 vs. 412 ± 8 ms, P < 0.01). During hyperglycaemia, the QTc dispersion was prolonged in healthy volunteers (36 ± 4 ms vs. 54 ± 7 ms, P < 0.05) but not in patients with Type 1 diabetes (45 ± 3 ms at baseline vs. 48 ± 5 ms, NS).Conclusions  Acute hyperglycaemia alters myocardial ventricular repolarization in patients with Type 1 diabetes and in healthy volunteers and might consequently be an additional risk factor for cardiovascular events.
Prediabetes and the big baby1
Authors: Hadden D. R. 
Published: September 2010

AbstractThe concept of prediabetes has come to the fore again with the worldwide epidemic of Type 2 diabetes. The careful observations of W. P. U. Jackson and his colleagues in Cape Town, South Africa 50 years ago still deserve attention. Maternal hyperglycaemia cannot be the only cause of fetal macrosomia, and the pathophysiological reason for the unexplained stillbirth in late diabetic pregnancy still eludes us. The biochemical concepts of ‘facilitated anabolism’ and ‘accelerated starvation’ were developed by Freinkel as explanations of the protective mechanisms for the baby during the stresses of pregnancy. Some of these nutritional stresses may also occur in the particular form of early childhood malnutrition known in Africa as kwashiorkor, where subcutaneous fat deposition, carbohydrate intolerance, islet hyperplasia and sudden death may follow a period of excess carbohydrate and deficient protein intake. Different feeding practices in different parts of the world make comparisons uncertain, but there is evidence for insulin resistance in both the macrosomic fetus of the hyperglycaemic mother and in the child with established kwashiorkor. These adaptive changes in early development may play both a physiological and a pathological role. Worldwide studies of hyperglycaemia in pregnancy are gradually establishing acceptable diagnostic criteria, appropriate screening procedures and an evidence base for treatment. Nevertheless the challenge of prediabetes and the big baby is still with us—in Jackson's words—‘diabetes mellitus is a fascinating condition—the more we know about it the less we understand it’.
The possible adaptive advantages of terrestrial egg deposition in some fluvial diadromous galaxiid fishes (Teleostei: Galaxiidae)
Authors: McDowall RM , Charteris SC 
Published: September 2010

AbstractSeveral diadromous New Zealand and Australian species of Galaxias are now known, or suspected, to deposit their eggs amongst riparian vegetation or substrates either supratidally in estuaries or in forested streams in locations that are only temporarily submerged by elevated water levels. The eggs develop in a humid atmosphere and hatch when the egg deposition sites are resubmerged; a significant role for agitation in stimulating hatching seeming likely. There are risks from the eggs becoming dehydrated, and also from a failure by water to resubmerge the eggs before they have exhausted their energy resources. Hatching is triggered by elevated flows, perhaps being an outcome of agitation of the eggs. Elevated flows may also increase the rate of downstream transport of the larvae, facilitating survival during dispersal to sea from spawning sites in streams that may be long distances inland. Hatching during flood events may favour survival of the larvae because turbid flows may provide ‘cover’ for the larvae as they emigrate to sea. Risks from egg predation by aquatic predators may be replaced by risks from terrestrial predators.
The Challenges of Climate Policy
Authors: Brennan Timothy J. 
Published: September 2010

Abstract Climate policy planners and the public should be aware of both economic challenges and arguments that may influence the intensity of the climate policies with which they have to cope. This article examines six economic challenges: cap‐and‐trade versus taxes, non‐price regulations, energy efficiency policies, mitigation versus adaptation, trade effects, and transmission planning. Three additional challenges affect the end itself: ‘fat tails’, discount rates, and whether environmental protection should be evaluated by willingness to pay. If future generations cannot compensate the present for climate policy costs, climate policy is inherently redistributive and cannot be evaluated through cost–benefit analysis alone.
THOMAS REID ON ACQUIRED PERCEPTION
Authors: COPENHAVER REBECCA 
Published: September 2010

AbstractThomas Reid's distinction between original and acquired perception is not merely metaphysical; it has psychological and phenomenological stories to tell. Psychologically, acquired perception provides increased sensitivity to features in the environment. Phenomenologically, Reid's theory resists the notion that original perception is exhaustive of perceptual experience. James Van Cleve has argued that most cases of acquired perception do not count as perception and so do not pose a threat to Reid's direct realism. I argue that acquired perception is genuine perception and as direct as original perception. Perception is grounded in a productive and developing relationship between the mind and world.
KANTIAN PRACTICAL LOVE
Authors: FAHMY MELISSA SEYMOUR 
Published: September 2010

AbstractIn the Doctrine of Virtue Kant stipulates that ‘Love is a matter of feeling, not of willing . . . so a duty to love is an absurdity.’ Nonetheless, in the same work Kant claims that we have duties of love to other human beings. According to Kant, the kind of love which is commanded by duty is practical love. This paper defends the view that the duty of practical love articulated in the Doctrine of Virtue is distinct from the duty of beneficence and best understood as a duty of self‐transformation, which agents observe by cultivating a benevolent disposition and practical beneficent desires.
LEXICAL PRIORITY AND THE PROBLEM OF RISK
Authors: HUEMER MICHAEL 
Published: September 2010

AbstractSome theories of practical reasons incorporate a lexical priority structure, according to which some practical reasons have infinitely greater weight than others. This includes absolute deontological theories and axiological theories that take some goods to be categorically superior to others. These theories face problems involving cases in which there is a non‐extreme probability that a given reason applies. In view of such cases, lexical‐priority theories are in danger of becoming irrelevant to decision‐making, becoming absurdly demanding, or generating paradoxical cases in which each of a pair of actions is permissible yet the pair is impermissible.
FOUNDATIONALLY JUSTIFIED PERCEPTUAL BELIEFS AND THE PROBLEM OF THE SPECKLED HEN
Authors: PACE MICHAEL 
Published: September 2010

AbstractMany epistemologists accept some version of the following foundationalist epistemic principle: if one has an experience as if p then one has prima facie justification that p. I argue that this principle faces a challenge that it inherits from classical foundationalism: the problem of the speckled hen. The crux of the problem is that some properties are presented in experience at a level of determinacy that outstrips our recognitional capacities. I argue for an amendment to the principle that adds to its antecedent the requirement that the subject have a recognitional capacity with respect to the given property.
Correlation risk, cross‐market derivative products and portfolio performance*
Authors: Ho T. S. , Stapleton Richard C. , Subrahmanyam Marti G. 
Published: September 2010

AbstractWe consider portfolios whose returns depend on at least three variables and show the effect of the correlation structure on the probabilities of the extreme outcomes of the portfolio return, using a multivariate binomial approximation. the portfolio risk is then managed by using derivatives. We illustrate this risk management both with simple options, whose payoff depends upon only one of the underlying variables, and with more complex instruments, whose payoffs (and values) depend upon the correlation structureThe question of benchmarking portfolio performance is complicated by the use of derivatives, especially complex derivatives, since these instruments fundamentally alter the distribution of returns. We use the multivariate binomial model to set performance benchmarks for multicurrency, international portfolios. Our model is illustrated using a simple example where a German institution invests a proportion of its funds in Germany equities and the remainder in UK equities. Portfolio performance is measured in Deutsche Marks and depends upon (1) the DAX index, (2) the FTSE index and (3) the Deutsche Mark‐Sterling exchange rate.The output of the model is a simulation of possible outcomes from the portfolio hedging strategy. the difference in our methodology is that we are able to retain the simplicity of the binomial distribution, used extensively in the analysis of options, in a multivariate context. This is achieved by building three (or more) binomial trees for the individual variables and capturing the correlation structure with the use of varying conditional probabilities.
The search for evidence of chaos in FTSE‐100 daily returns
Authors: Varson Paula L. , Doran Paul 
Published: September 2010

AbstractThis study provides an elementary discussion of deterministic chaos as it applies to security returns. the study demonstrates a simple technique, well known in the physical sciences, for discriminating between random and chaotic time‐series. Applying the technique to a time‐series of daily returns on the FTSE‐100, an index comprised of the stocks of the 100 largest British firms, results in evidence that the time‐series is random, not chaotic.
New Paradigms in Stock Market Indexing
Authors: Jun Derek , Malkiel Burton G. 
Published: September 2010

Abstract Considerable recent interest has been shown in a new set of stock‐market indices that are weighted by fundamental factors such as sales, earnings, dividends or book values, rather than by capitalization. In this paper, we analyze the performance of Fundamental Indexing™ (“FI”). First, we show that the source of FI's recent excellent performance is not from its ability to systematically arbitrage mispricing in a noisy market but from increasing the portfolio's exposure to stocks with low price‐to‐book values and with small capitalizations. We find that FI does not produce a positive alpha when its excess returns are explained by the Fama‐French three‐factor model of CAPM beta, the value premium and the size premium. Second, we show that it is possible to construct a portfolio of exchange‐traded funds with similar factor loadings that can replicate, and sometimes, even outperform FI. However, we caution investors not to expect consistent outperformance from portfolios tilted towards value and small‐cap stocks. Historical data shows evidence of mean reversion in the performance of such strategies.
The transnational politics of judicialization. Van Gend en Loos and the making of EU polity
Authors: Vauchez Antoine 
Published: September 2010

AbstractThis article tracks the genesis of one of the EU's most established meta‐narratives, that of Europeanisation‐through‐case‐law. Instead of studying this theory of European integration as an explanatory frame, I consider what is at stake in its genesis as a dominant frame of understanding of Europeanisation. I trace its emergence in the conflicting theorisations of the relationship between law and the European Communities that come along with the ECJ's ‘landmark’ decisions (Van Gend en Loos and Costa v ENEL). This approach helps seize the genesis of a specific and—at the time—rather unlikely political model for Europe in which a Court (the ECJ) is regarded as the very locus of European integration's dynamics as well as the best mediator and moderator of both Member States' ‘conservatism’ and individuals' ‘potential excesses’.