bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the Insulin‐antagonistic Effect of Growth Hormone in Insulin‐dependent Diabetes Mellitus
Authors: Fowelin J. , Attvall S. , Von Schenck H. , Smith U. , Lager I. 
Published: July 2009

To characterize its insulin‐antagonistic effect, growth hormone (GH) was infused at variable rates (24, 12 or 6 ***mU kg−1 min−1) for 1 h in 7 IDDM patients. Saline infusion was used as control (C) and all patients participated in all studies. The effect of insulin was measured with the euglycaemic clamp technique for 6 h combined with d–(3–3H)–glucose to evaluate glucose turnover. The insulin levels during the clamps were similar in all studies (23 ± 3 ***mU I−1). The infusions produced peak GH levels of (24 rate = 24) 157 ± 11, (12 rate = 12) 76 ± 7, and (6 rate = 6) 45 ± 8 ***mU 1−1 (mean ± SEM). The insulin‐antagonistic effect of GH on glucose uptake was seen after 2 h and was at a maximum 4 to 5 h after the start of the GH infusion (difference in glucose infusion rate between C and 24 was 1.7 ± 0.4 mg kg−1 min−1p < 0.01). The resistance was due to a less pronounced effect of insulin to both inhibit rate of appearance and to stimulate rate of disappearance. Infusion of GH at 12 mU kg−1 min−1 induced a less pronounced insulin resistance both with regards to maximal effect (glucose infusion rate C ‐ GH 1.4 ± 0.5 mg kg−1 min−1p < 0.05) and duration (3 h). At 6 ***mU kg−1 min−1a clear GH‐induced insulin‐antagonistic effect was only seen during the third hour of the clamp (glucose infusion rate C‐GH 1.3 ± 0.5 mg kg−1 min−1p < 0.05). GH infusion impaired the effect of insulin to lower both the levels of free fatty acids (NEFA) and glycerol between 2 and 5 h after the start of the infusion (NEFA, C:110 ± 29, 24:303 ± 95, p < 0.05: glycerol, C:32 ± 4, 24:50 ± 7 μmol I−1p < 0.05).The present study therefore demonstrates that the insulin‐antagonistic effect of GH in IDDM is related to the plasma levels both with regard to duration and response. The results also indicate that GH impairs the effect of insulin on lipolysis in IDDM after physiological peaks.
Microalbuminuria as Identified by a Spot Morning Urine Specimen in Non‐insulin‐treated Diabetes: an Eight‐year Follow‐up Study
Authors: Beatty O.L. , Ritchie C.M. , Bell P.M. , Hadden D.R. , Kennedy L. , Atkinson A.B. 
Published: July 2009

This study followed up a cohort of patients with microalbuminuria identified on a spot morning urine sample 8 years earlier and aimed to determine if a spot morning urinary albumin concentration was able to identify patients with non‐insulin treated diabetes at increased risk of mortality and progression to nephropathy.In 1984, 47 of 216 patients chosen by random selection from our teaching hospital‐based diabetes clinic were identified as having microalbuminuria (urinary albumin concentration 35–300 μg ml−1). Subjects were compared with an age‐matched control group from the 1984 cohort who did not have microalbuminuria. Eight years later, 22 of 47 (46.8 %) patients with microalbuminuria had died compared to 10 of 47 (21.3 %) patients without albuminuria (p < 0.05). The majority of deaths were from cardiovascular disease (53.1 %). Logistic regression showed microalbuminuria to be an independent predictor of mortality, not influenced by age, duration of diabetes, blood pressure, glycosylated haemoglobin or creatinine at the initial examination. Eight years later, in the group with initial microalbuminuria, eight still had microalbuminuria and five patients had developed nephropathy. In the group without albuminuria in 1984, only one patient had progressed to microalbuminuria and no patients to nephropathy. In conclusion, a spot urinary albumin concentration is of value in identifying patients with an increased risk of mortality or progression to nephropathy, and is simple to obtain at a clinic.
Beyond the Distinction between Positivism and Non‐Positivism*
Authors: PERRY STEPHEN 
Published: July 2009

AbstractIn this article I discuss a number of issues raised by Professor Jules Coleman's recent article “Beyond the Separability Thesis.” I suggest, to begin, that Coleman is correct that neither a narrow nor a broad formulation of the separability thesis takes us very far towards a robust distinction between legal positivism and legal non‐positivism. I then offer a brief discussion of methodology in jurisprudence, suggesting that Coleman accepts, at least implicitly, what I call a “methodology of necessary features.” Since there is reason to think that law possesses some necessary features that are non‐normative (or descriptive) and others that are moral in character, the promise of this pluralistic approach is that it will be capable of bridging the gap between so‐called “descriptive” and “normative” theories of methodology in jurisprudence. Since the distinction between descriptive and normative methodological theories is sometimes taken to be one way, among others, of drawing a distinction between positivist and non‐positivist theories of law, the pluralism of the “methodology of necessary features” gives us yet one more reason to think that the distinction between positivism and non‐positivism is not a theoretically fundamental one. Finally, I discuss Coleman's “moral semantics claim,” i.e., the idea that “legal content is best understood as moral directives about what is to be done and who is to decide what is to be done.” Coleman acknowledges that the moral semantics claim, when taken together with the social facts thesis, raises a well‐known problem: How can social facts create content‐independent reasons for action? I suggest that we are most likely to find the answer to this question by focusing directly on whether or not law's claimed moral authority—meaning its claimed moral power—can be justified, rather than by focusing indirectly, as many theorists have done, on the existence or non‐existence of a general obligation to obey the law.
Was Inclusive Legal Positivism Founded on a Mistake?
Authors: SHAPIRO SCOTT J. 
Published: July 2009

AbstractIn this paper, I present a new argument against inclusive legal positivism. As I show, any theory which permits morality to be a condition on legality cannot account for a core feature of legal activity, namely, that it is an activity of social planning. If the aim of a legal institution is to guide the conduct of the community through plans, it would be self‐defeating if the existence of these plans could only be determined through deliberation on the merits. I also argue that, insofar as inclusive legal positivism was developed as a response to Ronald Dworkin's critique of H. L. A. Hart's theory of law, it was founded on a mistake. For once we appreciate the role that planning plays in legal regulation, we will see that Dworkin's objection is based on a flawed conception of legal obligations and rights and hence does not present an objection that inclusive legal positivists were required to answer.
INTUITIVE NON‐NATURALISM MEETS COSMIC COINCIDENCE
Authors: BEDKE MATTHEW S. 
Published: July 2009

AbstractHaving no recourse to ways of knowing about the natural world, ethical non‐naturalists are in need of an epistemology that might apply to a normative breed of facts or properties, and intuitionism seems well suited to fill that bill. Here I argue that the metaphysical inspiration for ethical intuitionism undermines that very epistemology, for this pair of views generates what I call the defeater from cosmic coincidence. Unfortunately, we face not a happy union, but a difficult choice: either ethical intuitionism or ethical non‐naturalism, but not both.
THE PASSIONS OF PUNISHMENT
Authors: HANNA NATHAN 
Published: July 2009

AbstractI criticize an increasingly popular set of arguments for the justifiability of punishment. Some philosophers try to justify punishment by appealing to what Peter Strawson calls the reactive attitudes– emotions like resentment, indignation, remorse and guilt. These arguments fail. The view that these emotions commit us to punishment rests on unsophisticated views of punishment and of these emotions and their associated behaviors. I offer more sophisticated accounts of punishment, of these emotions and of their associated behaviors that are consistent with Abolitionism, the view that punishment is unjustified.
Conflicts of Interest and Research Quality of Affiliated Analysts in the German Universal Banking System: Evidence from IPO Underwriting
Authors: Bessler Wolfgang , Stanzel Matthias 
Published: July 2009

Abstract The quality of equity research by financial analysts is a prerequisite for an efficient capital market. This study investigates the quality of earnings forecasts and stock recommendations for initial public offerings (IPOs) in Germany. The empirical study includes 12,605 earnings forecasts and 6,209 stock recommendations of individual analysts for the time period from 1997 to 2004. The focus of this study is on analysing the potential conflicts of interest that arise when the analyst is affiliated with the underwriter of an IPO. In a universal banking system these conflicts of interest are usually more pronounced and therefore interesting to investigate. The empirical findings for the German financial market suggest that earnings forecasts and stock recommendations of the analysts belonging to the lead‐underwriter are on average inaccurate and biased, indicating some conflicts of interest. Moreover, the stock recommendations of the analysts that are affiliated with the lead‐underwriter are often too optimistic resulting in a significant long‐run underperformance for the investor. In contrast, unaffiliated analysts provide better earnings forecasts and stock recommendations that result in a superior performance for the investor.
Migration Prediction On The Basis Of Prior Migratory Behavior: A Methodological Note
Authors: Rogers T. W. 
Published: July 2009

ABSTRACTStochastic process analysis, particularly Markov chain dependence, may be utilized in a wide range of research situations where change through time is the focus of interest. This paper is concerned with the utility of Markov chain analysis in the prediction of future migration on the basis of past migratory behavior. Transition probability matrices, which were dependent on the respondent's migratory behavior in the preceding time interval, were utilized to predict migration in the following time interval for a series of 145 longitudinal case histories. Predictions were also obtained for selected age, educational, and occupational stratifications. Markov chain analysis, or a similar probability model, seems to provide a promising tool for studying the relationship between prior and expected migration, and for obtaining statements of migration probability. Since a high proportion of total migrations seem to be made by a limited segment of the population, the factor of past migratory behavior itself may be an important element in the identification of migration differentials and the prediction of future migration.
Immigrants and Refugees: Their Similarities, Differences, and Needs
Authors: BERNARD WILLIAM S. 
Published: July 2009

In December 1976, the Director of the Intergovernmental Committee for European Migration (ICEM), Mr. John F. Thomas, addressed a Seminar of the American Immigration and Citizenship Conference in New York, where the author of this article, Dr William S. Bernard, Chairman of the Committee on lntegration of the American Immigration and Citizenship Conference and Emeritus Director of the Center for Migration Studies, Brooklyn College, City University of New York, was honoured for his eminent work and contributions on the world‐wide problems of voluntary and forced migratory movements and especially the human aspectsinvolved.The editors of International Migrarion hope that this eminent author will also in future con‐ tribute his valuable articles to this periodical.
Obtaining the views of children and young people with autism spectrum disorders about their experience of daily life and social care support
Authors: Preece David , Jordan Rita 
Published: July 2009

Accessible summary Children with autism spectrum disorders (aged 7–18 years) were interviewed about their experience of living at home and in short term care. Parents and caregivers were also interviewed and, when the child had little or no speech, he or she was observed in both settings. Pictures and schedules were used to prompt the children but using them, or allowing parents to interrupt, sometimes made it difficult to be sure that the children’s views were completely their own. It was also important to use questions that meant something to the children. The children were generally happy with their life at home. Those who went for short‐term breaks liked some activities and individuals, but some did not like the noise and the rules.SummaryChildren with autism spectrum disorders (10 boys and 4 girls aged 7 to 18 years) from a shire county in England were interviewed as part of a study examining the experience and attitudes of families towards daily life and short breaks support. Techniques for obtaining consent and eliciting the children’s views are detailed, including triangulation of data. Data were collected on the children’s experience of day‐to‐day life, social workers, and short breaks services, and their wishes. Qualitative data analysis was undertaken using a template approach. The children were positive about family life, although most activities reported were solitary. None understood the role of social workers. Those who attended short breaks enjoyed some activities and peers’ company but were disturbed by noise and staff discipline. Difficulties faced in carrying out the research, and limitations arising from the research methods and the nature of ASD are acknowledged, and factors that were helpful in the process are identified.
Non‐indigenous ungulates as a threat to biodiversity
Authors: Spear D. , Chown S. L. 
Published: July 2009

AbstractNon‐indigenous ungulate species pose a problem for conservation. They can be socially and economically valuable, but are also potentially harmful to biodiversity. Therefore, their introduction requires an explicit assessment of risk relative to benefit. To conduct such risk assessments, information regarding the impacts of non‐indigenous ungulates on biodiversity is required. Here, we review the available evidence for the biodiversity impacts of non‐indigenous ungulates. Hybridization, exploitation and apparent competition, vegetation impacts, predation, facilitation, trophic cascades and soil system functioning were assessed using a hierarchical set of criteria for the strength of the evidence. Strong evidence was lacking for risks posed by competition. Numerous reports exist of hybridization in captivity between ungulate species that normally do not co‐occur, but conclusive evidence for introgression in the wild was restricted to one case. Strong evidence (using exclosure experiments) for the impacts of introduced ungulates on vegetation structure and composition was found and in some cases introduced ungulates caused the extirpation of plant species. Predation bySus scrofais a substantial threat to island faunas and systems, and impacts on soil system functioning elsewhere have also been found. Facilitation by ungulates has been shown to be substantial in promoting invasive plant species. By contrast, little evidence exists for apparent competition. The largest impacts from introduced ungulates are likely to be in cases where they perform novel functions in the new environment. However, to determine which types of impacts are likely to be most problematic, further evidence is required, ideally from well‐designed field experiments.
Benefit of therapeutic drug monitoring of protease inhibitors in HIV‐infected patients depends on PI used in HAART regimen – ANRS 111 trial
Authors: Duval Xavier , Mentré France , Rey Elisabeth , Auleley Solange , Peytavin Gilles , Biour Michel , Métro Annie , Goujard Cecile , Taburet Anne‐Marie , Lascoux Cecile , Panhard Xaviere , Tréluyer Jean‐Marc , Salmon‐Céron Dominique ,   the Cophar 2 study group
Published: July 2009

AbstractAs a result of high inter‐patient variability, and efficacy–concentration and toxicity–concentration relationships, optimization of HIV‐protease inhibitor (PI) doses based on plasma concentrations could be beneficial. During a 48‐week open prospective non‐randomized interventional study of 115 protease inhibitor‐naïve patients initiating an indinavir/ritonavir‐ or lopinavir/ritonavir‐, or nelfinavir‐containing therapy, protease inhibitor dose was modified when plasma trough concentrations (Ctrough) at weeks 2, 8, 16 and 24 were outside predefined optimal concentration ranges. Failure of the strategy was defined as the proportions of patients with HIV‐RNA above 200 copies/mL from weeks 24 to 48 and/or experiencing grades 2, 3 or 4 PI‐related adverse events during the study; proportion of patients with last Ctrough measurement outside the concentration range was determined at each visit. Virological failure and/or occurrence of adverse event were observed in 37/94 assessable patients (39%; 95% CI: 29.4–50.0). In the on‐treatment analysis, failure of the strategy was noted in 16% of indinavir/r‐ or lopinavir/r‐treated patients (8/51; 95% CI: 7.0–28.6; virological failure: 2; adverse event: 6) but in 44% of nelfinavir‐treated patients (11/25; 95% CI: 24.4–65.1; virological failure: 10; adverse event: 1); Ctrough concentrations outside the range were less frequent at the last measurement than at W2 (41% vs. 66%; P < 0.05), with proportions of 35% for indinavir/r‐ or lopinavir/r‐treated patients, but 57% for nelfinavir‐treated patients. The proposed strategy of therapeutic drug monitoring may be beneficial to indinavir/r‐ and lopinavir/r‐treated patients, but failed to move concentrations into the predefined range and to produce the expected virological success for nelfinavir‐treated patients.
Pharmacological screening of bryophyte extracts that inhibit growth and induce abnormal phenotypes in human HeLa cancer cells
Authors: Krzaczkowski Lucie , Wright Michel , Rebérioux Delphine , Massiot Georges , Etiévant Chantal , Gairin Jean Edouard 
Published: July 2009

AbstractAntitumor activities of substances from natural sources apart from vascular plants and micro‐organisms have been poorly investigated. Here we report on a pharmacological screening of a bryophyte extract library using a phenotypic cell‐based assay revealing microtubules, centrosomes and DNA. Among the 219 moss extracts tested, we identified 41 extracts acting on cell division with various combinations of significant effects on interphasic and mitotic cells. Seven extracts were further studied using a cell viability assay, cell cycle analysis and the phenotypic assay. Three distinct pharmacological patterns were identified including two unusual phenotypes.
Anti‐diarrhoeal and ulcer‐protective effects of violacein isolated fromChromobacterium violaceumin Wistar rats
Authors: Antonisamy Paulrayer , Kannan Ponnusamy , Ignacimuthu Savarimuthu 
Published: July 2009

AbstractViolacein was isolated fromChromobacterium violaceum, a soil Gram‐negative bacterium collected from the forest water body soil sample from Kolli Hills of Tamil Nadu, India. In the present study the anti‐diarrhoeal and ulcer‐protective properties of violacein were investigated in Wistar rats using castor oil, magnesium sulphate and ethanol. The intestinal transit in rats was significantly (P < 0.001) reduced and gastric emptying was delayed; 40 mg/kg of violacein elicited a greater anti‐motility activity than 0.1 mg/kg of atropine. Violacein exhibited ulcer‐protective properties against ethanol‐induced ulceration in rats with maximal anti‐ulcer activity at 40 mg/kg. Violacein also exerted significant anti‐enteropooling effects, causing a dose‐related inhibitory effect on castor oil‐induced enteropooling in rats. A profound anti‐diarrhoeal activity was observed when violacein was tested in diarrhoeic rats. The frequencies of defaecation as well as the wetness of the faecal droppings were significantly reduced. Furthermore, violacein (40 mg/kg) produced 87.84% inhibition of castor oil‐induced diarrhoea in rats. The results suggested that violacein can be used for the treatment of diarrhoeal and ulcer‐related diseases.
Effect of coadministered HIV‐protease inhibitors on tacrolimus and sirolimus blood concentrations in a kidney transplant recipients
Authors: Barau Caroline , Blouin P. , Creput Caroline , Taburet A.M. , Durrbach Antoine , Furlan Valérie 
Published: July 2009

AbstractA patient with human immunodeficiency virus infection and end‐stage renal disease received a renal transplant. At the time of surgery, the patient was on quadruple antiretroviral therapy (lamivudine, zidovudine, and amprenavir/ritonavir). Immunosuppression was initiated with basiliximab, corticosteroid, mycophenolate mofetil, and a single 0.5 mg dose of tacrolimus. In the following days, an increase in tacrolimus concentration was observed with a peak of 37 ng/mL. Tacrolimus half‐life was 6.5 days and tacrolimus maintenance dose was 0.5 mg every 4 days. Eleven months later, the patient had developed Kaposi sarcoma. Tacrolimus was replaced by sirolimus (first dose 1 mg), and the patient was stabilized with 1.5 mg of sirolimus once a week. Increased tacrolimus half‐life and increased dose interval of sirolimus and tacrolimus were due to CYP3A4/5 and/or P‐glycoprotein inhibition by protease inhibitors. Close monitoring is required in the management of tacrolimus and sirolimus dosing regimens when combined with ritonavir boosted HIV‐1 protease inhibitors.
Current status of malaria chemotherapy and the role of pharmacology in antimalarial drug research and development
Authors: Na‐Bangchang Kesara , Karbwang Juntra 
Published: July 2009

AbstractAntimalarial drugs have played a mainstream role in controlling the spread of malaria through the treatment of patients infected with the plasmodial parasites and controlling its transmissibility. The inadequate armory of drugs in widespread use for the treatment of malaria, development of strains resistant to currently used antimalarials, and the lack of affordable new drugs are the limiting factors in the fight against malaria. In addition, other problems with some existing agents include unfavorable pharmacokinetic properties and adverse effects/toxicity. These factors underscore the continuing need of research for new classes of antimalarial agents, and a re‐examination of the existing antimalarial drugs that may be effective against resistant strains. In recent years, major advances have been made in the pharmacology of several antimalarial drugs both in pharmacokinetics and pharmacodynamics aspects. These include the design, development, and optimization of appropriate dosage regimens of antimalarials, basic knowledge in metabolic pathways of key antimalarials, as well as the elucidation of mechanisms of action and resistance of antimalarials. Pharmacologists have been working in close collaboration with scientists in other disciplines of science/biomedical sciences for more understanding on the biology of the parasite, host, in order to exploit rational design of drugs. Multiple general approaches to the identification of new antimalarials are being pursued at this time. All should be implemented in parallel with focus on the rational development of new agents directed against newly identified parasite targets. With major advances in our understanding of malaria parasite biology coupled with the completion of the malaria genome, has presented exciting opportunities for target‐based antimalarial drug discovery.