bluuebunny/crossref_metadata_2025 huggingface dataset:
Non‐food/feed seeds as biofactories for the high‐yield production of recombinant pharmaceuticals
Authors: Morandini Francesca , Avesani Linda , Bortesi Luisa , Van Droogenbroeck Bart , De Wilde Kirsten , Arcalis Elsa , Bazzoni Flavia , Santi Luca , Brozzetti Annalisa , Falorni Alberto , Stoger Eva , Depicker Ann , Pezzotti Mario
Published: April 2011

We describe an attractive cloning system for the seed‐specific expression of recombinant proteins using three non‐food/feed crops. A vector designed for direct subcloning by Gateway® recombination was developed and tested in Arabidopsis, tobacco and petunia plants for the production of a chimeric form (GAD67/65) of the 65 kDa isoform of glutamic acid decarboxylase (GAD65). GAD65 is one of the major human autoantigens involved in type 1 diabetes (T1D). The murine anti‐inflammatory cytokine interleukin‐10 (IL‐10) was expressed with the described system in Arabidopsis and tobacco, whereas proinsulin, another T1D major autoantigen, was expressed in Arabidopsis. The cost‐effective production of these proteins in plants could allow the development of T1D prevention strategies based on the induction of immunological tolerance. The best yields were achieved in Arabidopsis seeds, where GAD67/65 reached 7.7% of total soluble protein (TSP), the highest levels ever reported for this protein in plants. IL‐10 and proinsulin reached 0.70% and 0.007% of TSP, respectively, consistent with levels previously reported in other plants or tissues. This versatile cloning vector could be suitable for the high‐throughput evaluation of expression levels and stability of many valuable and difficult to produce proteins.
Political and Fiscal Risk Determinants of Sovereign Spreads in Emerging Markets
Authors: Baldacci Emanuele , Gupta Sanjeev , Mati Amine
Published: April 2011

Using a panel of 46 emerging market economies from 1997 to 2008, this paper investigates the key determinants of country risk premiums as measured by sovereign bond spreads. Unlike previous studies, the results indicate that both political and fiscal factors matter for credit risk in emerging markets. Lower levels of political risk are associated with tighter spreads, particularly during financial turmoil. Efforts at fiscal consolidation narrow credit spreads, especially in countries with high initial public debt levels. The composition of fiscal policy also matters as higher public investment lowers spreads as long as the fiscal position remains sustainable and the fiscal deficit does not worsen.
Origin of FDI and Intra‐Industry Domestic Spillovers: The Case of Greek and European FDI in Bulgaria
Authors: Monastiriotis Vassilis , Alegria Rodrigo
Published: April 2011

This paper uses firm‐level data to assess the horizontal impact of foreign firm ownership on domestic productivity in Bulgaria. We identify a theoretical tradeoff between technological distance (of domestic versus foreign firms) and internalization capacity (of spillovers) and examine the extent to which this is reflected in the impact on the domestic economy of different types and origins of FDI. Emphasis is placed upon the effects of Greek FDI, which is known to be of a distinctively “regional” character. We find that Greek FDI produces significantly larger positive spillovers, which appear more suitable for the Bulgarian context of transition and economic restructuring. We also unveil some notable “hysteresis” and “technology bias” effects for FDI spillovers of all origins, as well as some country‐specific ownership‐structure and threshold effects.
A Two‐Country Game of Competition Policies
Authors: Yano Makoto , Honryo Takakazu
Published: April 2011

Recently a number of studies have recognized that trade policy can be substituted for by competition policy. This study demonstrates, however, that there is a fundamental difference in the working of terms‐of‐trade effects between competition policy and tariff policy and that if countries optimally set their respective competition policies, it is unlikely to result in a tariff‐war‐like state in which all countries adopt distortionary policies. Instead, in a Nash equilibrium, one country maintains perfect competition in its domestic service sector while the other country tolerates imperfect competition.
Tariff, Growth, and Welfare
Authors: Lee Shun‐Fa
Published: April 2011

We develop a two‐country (Home and Foreign) by two‐good (consumption good and investment good) by one factor (capital) endogenous growth model with international knowledge spillover to study the relationship between an import tariff and economic growth and welfare. First, unlike the past literature, we do not need to make an assumption such that the growth rates between countries are identical in a balanced growth path (BGP). Second, we show that there exists a unique and saddle‐point BGP with both countries being incompletely specialized. Third, a higher import tariff on the consumption good in the domestic country may boost (reduce) the rate of economic growth when the foreign (domestic) country has an absolute advantage in the investment good. Finally, a rise in the tariff rate by one country may improve world welfare under some parameter spaces.
Division of Labor and Endogenous Comparative Advantage: A Smith–Ricardian Model of International Trade
Authors: Yu Zhihao
Published: April 2011

This paper develops a Smith–Ricardian model that incorporates division of labor into the continuum‐good Ricardian model of Dornbusch et al. (1977). The tradeoff between the efficiency gain and coordination cost in production determines the efficient level of division of labor. Consequently, the traditional comparative advantage becomes endogenous. The model is able to explain how the recent progress in information technology (IT) would affect the efficient level of division of labor and competitive margin. In particular, we show that absolute advantage in division of labor and relative labor supply play a crucial role in determining the different effects of universal IT progress on a country's competitive margin in international trade.
Forming Efficient Free‐Trade Networks: A Sequential Mechanism
Authors: Zhang Jin , Xue Licun , Yin Xiaopeng
Published: April 2011

This paper considers a sequential network formation game, whose subgame‐perfect equilibrium can generate an efficient and complete network as the equilibrium outcome, thereby achieving global free trade. Our result shows that bilateral free‐trade agreements can be compatible with global free trade.
A Stain on the White Uniform — The Discursive Construction of Nurses' Industrial Action in the Media
Authors: Henttonen Elina , LaPointe Kirsi , Pesonen Sinikka , Vanhala Sinikka
Published: April 2011

This article focuses on the discursive construction of the nursing profession in the context of an industrial action. Drawing on studies that claim that the diffusion of new public management reforms restructure healthcare professions and on feminist studies arguing that gender is crucial to understanding the concepts and processes of this restructuring, the article examines a media debate surrounding a recent labour dispute in the Finnish healthcare sector. The analysis illustrates how the nursing profession was discursively constructed through a negotiation of individual and societal rights and responsibilities, and how the debate was framed by competing and contested discourses of professionalization, caring, labour markets and new public management. As a consequence, the debate both sustained and reproduced the traditional gendered meanings related to the nursing profession, as well as provided a context for unsettling, at least for a moment, the normative gender order of Finnish society.
The Distorting Impact of Capital Controls
Authors: El-Shagi Makram
Published: April 2011

This paper uses panel data to show that capital controls have a significant impact on international interest rate differentials. Various types of controls can be distinguished within the data. The analysis shows that the aforementioned effects of capital controls on interest rates are especially strong in the case of capital import controls on portfolio capital; the implementation of these controls has been suggested in the wake of the Asian Crisis to prevent further crises. The results presented herein contradict the hypothesis that capital controls can achieve a restructuring of the maturity of capital inflows without a distortion in international capital allocation.
ON THE GROWTH CURVES OF CERTAIN CHARACTERS IN MAN (MALES)
Authors: RUGER HENRY A. , STOESSIGER BRENDA
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
INFANT MORTALITY IN THE METROPOLITAN BOROUGHS IN RELATION TO OCCUPATIONS
Authors: STOCKS PERCY
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
SOME NEW PEDIGREES OF HEREDITARY DISEASE
Authors: BELL JULIA
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
AN INQUIRY INTO VARIOUS DEATH‐RATES AND THE COMPARATIVE INFLUENCE OF CERTAIN DISEASES ON THE DURATION OF LIFE
Authors: KARN M. NOEL
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
ON THE INHERITANCE OF DURATION OF LIFE AND CAUSE OF DEATH
Authors: STOESSIGER BRENDA
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
THE FIDUCIAL ARGUMENT IN STATISTICAL INFERENCE
Authors: FISHER R. A.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
THE DETECTION OF LINKAGE WITH “DOMINANT” ABNORMALITIES
Authors: FISHER R. A.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
A TEST OF THE SUPPOSED PRECISION OF SYSTEMATIC ARRANGEMENTS
Authors: BARBACKI S. , FISHER R. A.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
GENETIC LINKAGE IN GRADED HUMAN CHARACTERS
Authors: PENROSE L. S.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
A HITHERTO UNEXPECTED COMPLICATION IN THE GENETICS OF HUMAN RECESSIVES
Authors: HALDANE J. B. S.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
A NOTE ON THE ARRANGEMENT OF INCOMPLETE BLOCKS, WHEN k= 3 AND λ= 1
Authors: SAVUR S. R.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
ADJUSTMENT OF A RATIO
Authors: UVEN M. J. van
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
MICROSPERMIA IN AN INDIVIDUAL FROM A FAMILY OF UNUSUALLY HIGH SEX RATIO AND LOW FERTILITY
Authors: HARRIS H.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
SOME NOTES ON DISCRIMINATION
Authors: PENROSE L. S.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
SOME EXAMPLES OF DISCRIMINATION
Authors: SMITH CEDRIC A. B.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
THE EFFECT OF MATERNAL AGE ON THE MANIFESTATION OF A POLYDACTYL GENE IN MICE
Authors: HOLT S. B.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
SOME OBSERVATIONS ON HEREDITY IN BREAST CANCER AND LEUKEMIA
Authors: BUSK Th.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
PARENTAL AND FRATERNAL CORRELATIONS FOR FITNESS
Authors: HALDANE J. B. S.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
THE TRUNCATED BINOMIAL DISTRIBUTION
Authors: FINNEY D. J.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
LINKAGE DATA FROM A FAMILY OF RENAL GLYCOSURICS
Authors: HOUSTON J. C.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
BIRTH WEIGHT, GESTATION TIME AND SURVIVAL IN SIBS
Authors: KARN MARY N. , LANG‐BROWN HELEN , MacKENZIE HELEN , PENROSE L. S.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
A TEST FOR HETEROGENEITY OF PROPORTIONS
Authors: SMITH C. A. B.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
SEASONAL VARIATION IN THE INDIAN BIRTH‐RATE
Authors: KOSAMBI D. D. , RAGHAVACHARI S.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
BIRTH WEIGHT AND LENGTH OF GESTATION OF TWINS, TOGETHER WITH MATERNAL AGE, PARITY AND SURVIVAL RATE
Authors: KARN MARY N.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
ALBINISM IN SOUTH‐WESTERN NIGERIA
Authors: BARNICOT N. A.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
TWIN DATA: A FURTHER STUDY OF BIRTH WEIGHT, GESTATION TIME, MATERNAL AGE, ORDER OF BIRTH, AND SURVIVAL
Authors: KARN MARY N.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
Eugenics and Modern Biology: Critiques of Eugenics, 1910–1945
Authors: Allen Garland E.
Published: April 2011

Eugenics in most western countries in the first four decades of the 20th century was based on the idea that genes control most human phenotypic traits, everything from physical features such as polydactyly and eye colour to physiological conditions such as the A‐B‐O blood groups to mental and personality traits such as “feeblemindedness,” alcoholism and pauperism. In assessing the development of the eugenics movement—its rise and decline between 1900 and 1950—it is important to recognise that its naïve assumptions and often flawed methodologies were openly criticised at the time by scientists and nonscientists alike. This paper will present a brief overview of the critiques launched against eugenicists’ claims, particularly criticisms of the American school led by Charles B. Davenport. Davenport's approach to eugenics will be contrasted to his British counterpart, Karl Pearson, founder and first editor of theAnnals of Eugenics.It was not the case that nearly everyone in the early 20th century accepted eugenic conclusions as the latest, cutting‐edge science. There are lessons from this historical approach for dealing with similar naïve claims about genetics today.
Effects of coagulant type on the physicochemical and organoleptic properties of Kashar cheese
Authors: YASAR KURBAN , GUZELER NURAY
Published: April 2011

Kashar cheeses were manufactured using different coagulants (calf rennet, chymosin derived by fermentation and proteases from Rhizomucor miehei and Cryphonectria parasitica) and ripened for 90 days. Use of different coagulants did not influence the dry matter, fat, protein, salt, pH, titratable acidity, total free fatty acids and texture profile analyses. The levels of water‐soluble nitrogen, 12% trichloroacetic acid‐soluble nitrogen, and for 5% phosphotungstic acid‐soluble nitrogen, the sensory properties were significantly influenced by the use of different coagulants. β‐casein was more hydrolysed in the cheese manufactured using protease from Cryphonectria parasitica than the other cheeses during 90 d of ripening.
Cost‐effectiveness of human papillomavirus vaccination and cervical cancer screening in Thailand
Authors: Sharma M , Ortendahl J , van der Ham E , Sy S , Kim JJ
Published: April 2011

Please cite this paper as:Sharma M, Ortendahl J, van der Ham E, Sy S, Kim J. Cost‐effectiveness of human papillomavirus vaccination and cervical cancer screening in Thailand. BJOG 2012;119:166–176.

Objective To assess the health and economic outcomes of various screening and vaccination strategies for cervical cancer prevention.

Design Cost‐effectiveness analysis from a societal perspective.

Setting Thailand.

Population Females aged 9 years and older.

Methods Using a mathematical model of human papillomavirus (HPV) infection and cervical cancer, calibrated to epidemiological data from Thailand, we estimated the cost‐effectiveness of pre‐adolescent HPV vaccination, screening [visual inspection with acetic acid (VIA), HPV DNA testing, and cytology] between one and five times per lifetime in adulthood, and combined pre‐adolescent vaccination and screening. Vaccine efficacy, coverage, cost, and screening frequency were varied in sensitivity analyses.

Main outcome measures Incremental cost‐effectiveness ratios, expressed as cost per year of life saved (YLS).

Results Assuming lifelong efficacy and 80% coverage, pre‐adolescent HPV vaccination alone was projected to reduce the lifetime risk of cervical cancer by 55%, which was greater than any strategy of screening alone. When cost per vaccinated girl was I$10 (approximately $2 per dose) or less, HPV vaccination alone was cost saving. Pre‐adolescent vaccination and HPV DNA testing five times per lifetime, starting at age 35 years, reduced the lifetime cervical cancer risk by 70%, and had a cost‐effectiveness ratio less than Thailand’s GDP per capita (I$8100), provided the cost per vaccinated girl was I$200 or less.

Conclusions Low cost pre‐adolescent HPV vaccination followed by HPV screening five times per lifetime is an efficient strategy for Thailand. Costs may need to be lower, however, for this strategy to be affordable. If vaccination is not feasible, HPV DNA testing five times per lifetime is efficient.
A single‐nucleotide polymorphism in the TP53 and MDM‐2 gene modifies breast cancer risk in an ethnic Arab population
Authors: Alshatwi Ali A. , Hasan Tarique N. , Shafi Gowhar , Alsaif Mohammed A. , Al‐Hazzani Amal A. , Alsaif Adulaziz A.
Published: April 2011

Breast cancer is the most common oncological disease in women worldwide. Genetic predisposition to breast cancer can be associated with single‐nucleotide polymorphisms (SNPs), which are observed in many women. Such gene polymorphisms, in combination with nutritional and environmental factors, can affect breast cancer development. The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case–control studies have revealed that TP53 72Arg > Pro and MDM2 309T > G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and breast cancer susceptibility in the Saudi population has not been explored. In this study, we performed a case–control study of patients with breast cancer and healthy controls in a Saudi population using TaqMan‐based real‐time PCR. We found an increased breast cancer risk associated with the MDM2 GG [odds ratio (OR) = 2.79, 95% confidence interval (CI) = 2.04–3.92] and TG [OR = 1.43, 95% CI = 1.12–2.02] genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.19, 95% CI = 1.54–3.06) compared with the Arg/Arg genotype. The gene–gene interaction of MDM2 and TP53 polymorphisms increased breast cancer risk in a multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.71, 95% CI = 3.49–17.54). These findings suggest that polymorphisms of MDM2 and TP53 genes may be a genetic modifier for developing breast cancer in this ethnic population in the Arab world.
Expression of Concern: Role of LOX/COX pathways in 3‐nitropropionic acid‐induced Huntington's Disease‐like symptoms in rats: protective effect of licofelone
Authors: Kumar Puneet , Kalonia Harikesh , Kumar Anil
Published: April 2011

BACKGROUND AND PURPOSE Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by a degeneration of striatal neurons. The possible role of COX and lipoxygenase (LOX) pathways has been well‐documented in the pathology of several neurodegenerative disorders including HD. Licofelone is a competitive inhibitor of COX‐1– and COX‐2 and 5‐LOX isoenzymes. Therefore, the present study was designed to investigate possible neuroinflammatory and apoptotic mechanisms in the neuroprotective effect of licofelone against 3‐nitropropionic acid (3‐NP)‐induced HD‐like symptoms in rats.

EXPERIMENTAL APPROACH Rats were administered 3‐NP (10 mg·kg−1day−1, i.p.) for 14 days. Licofelone (2.5, 5 and 10 mg·kg−1, p.o.) was given once a day, 1 h before 3‐NP treatment for 14 days. Body weight and behavioural parameters (locomotor and rotarod activity) were assessed on the 1st, 5th, 10th and 15th day post‐3‐NP administration. Malondialdehyde, nitrite concentration, endogenous antioxidant enzymes (superoxide dismutase and catalase levels), mitochondrial enzyme complexes, pro‐inflammatory compounds (TNF‐α, IL‐6, NF‐κB), PGs (PGE2 and PGF2α) and caspase‐3 activity were measured on day 15 in the striatum.

KEY RESULTS Systemic 3‐NP treatment significantly reduced body weight, locomotor activity, oxidative defence, mitochondrial enzyme complex activities and increased TNF‐α, IL‐6, caspase‐3 activity, NF‐κB and PGE2 and PGF2α levels in the striatum. Licofelone (2.5, 5 and 10 mg·kg−1) significantly attenuated the impairment in behavioural, biochemical and mitochondrial, pro‐inflammatory and pro‐apoptotic markers as compared with vehicle‐treated group.

CONCLUSIONS AND IMPLICATIONS The results demonstrate the involvement of pro‐inflammatory compounds and the apoptotic cascade in the neuroprotective effect of licofelone against 3‐NP‐induced neurotoxicity.
Effects of inhibitors of hydrogen sulphide synthesis on rat colonic motility
Authors: Gil V , Gallego D , Jiménez M
Published: April 2011

BACKGROUND AND PURPOSE The role of hydrogen sulphide (H2S) as a putative endogenous signalling molecule in the gastrointestinal tract has not yet been established. We investigated the effect of D,L‐propargylglycine (PAG), an inhibitor of cystathionine γ‐lyase (CSE), amino‐oxyacetic acid (AOAA) and hydroxylamine (HA), inhibitors of cystathionine β‐synthase (CBS) on rat colonic motility.

EXPERIMENTAL APPROACH Immunohistochemistry, H2S production, microelectrode and organ bath recordings were performed on rat colonic samples without mucosa and submucosa to investigate the role of endogenous H2S in motility.

KEY RESULTS CSE and CBS were immunolocalized in the colon. H2S was endogenously produced (15.6 ± 0.7 nmol·min−1·g−1 tissue) and its production was strongly inhibited by PAG (2 mM) and AOAA (2 mM). PAG (2 mM) caused smooth muscle depolarization and increased spontaneous motility. The effect was still recorded after incubation with tetrodotoxin (TTX, 1 µM) or Nω‐nitro‐L‐arginine (L‐NNA, 1 mM). AOAA (2 mM) caused a transient (10 min) increase in motility. In contrast, HA (10 µM) caused a ‘nitric oxide‐like effect’, smooth muscle hyperpolarization and relaxation, which were antagonized by 1H‐[1,2,4]oxadiazolo[4,3‐α]quinoxalin‐1‐one (ODQ, 10 µM). Neither spontaneous nor induced inhibitory junction potentials were modified by AOAA or PAG.

CONCLUSIONS AND IMPLICATIONS We demonstrated that H2S is endogenously produced in the rat colon. PAG and AOAA effectively blocked H2S production. Our data suggest that enzymatic production of H2S regulates colonic motility and therefore H2S might be a third gaseous inhibitory signalling molecule in the gastrointestinal tract. However, possible non‐specific effects of the inhibitors should be considered.
Conversations in end‐of‐life care: communication tools for critical care practitioners
Authors: Shannon Sarah E. , Long‐Sutehall Tracy , Coombs Maureen
Published: April 2011

Background: Communication skills are the key for quality end‐of‐life care including in the critical care setting. While learning general, transferable communication skills, such as therapeutic listening, has been common in nursing education, learning specific communication tools, such as breaking bad news, has been the norm for medical education. Critical care nurses may also benefit from learning communication tools that are more specific to end‐of‐life care.

Strategy: We conducted a 90‐min interactive workshop at a national conference for a group of 78 experienced critical care nurses where we presented three communication tools using short didactics. We utilized theatre style and paired role play simulation. The Ask‐Tell‐Ask, Tell Me More and Situation‐Background‐Assessment‐Recommendation (SBAR) tools were demonstrated or practiced using a case of a family member who feels that treatment is being withdrawn prematurely for the patient. The audience actively participated in debriefing the role play to maximize learning. The final communication tool, SBAR, was practiced using an approach of pairing with another member of the audience. At the end of the session, a brief evaluation was completed by 59 nurses (80%) of the audience.

Summary: These communication tools offer nurses new strategies for approaching potentially difficult and emotionally charged conversations. A case example illustrated strategies for applying these skills to clinical situations. The three tools assist critical care nurses to move beyond compassionate listening to knowing what to say. Ask‐Tell‐Ask reminds nurses to carefully assess concerns before imparting information. Tell Me More provides a tool for encouraging dialogue in challenging situations. Finally, SBAR can assist nurses to distill complex and often long conversations into concise and informative reports for colleagues.
Should Ribavirin Be Used to Treat Hepatitis C in Dialysis Patients?
Authors: Carrion Andres F. , Fabrizi Fabrizio , Martin Paul
Published: April 2011

Hepatitis C virus infection adversely affects outcomes in patients with chronic kidney disease undergoing maintenance dialysis. Pegylated interferon and ribavirin, the standard‐of‐care treatment in patients with intact renal function, is associated with severe side effects, toxicity, and high dropout rates in this population. Ribavirin has an important role in maintaining antiviral response following completion of therapy and increases sustained viral response (SVR) rates. However, the use of ribavirin in dialysis patients has been limited by the high frequency of severe hemolytic anemia and is currently reserved for study protocols and highly selected candidates treated at experienced centers. Encouraging data from small trials have shown a significant increase in SVR rates with the use of different dosing regimens of ribavirin in addition to interferon‐based therapy and aggressive erythroid‐stimulating agent support in dialysis patients. Use of ribavirin in selected dialysis patients, particularly renal transplant candidates, by experienced clinicians is appropriate.
A Large Pleural Effusion in a Patient Receiving Peritoneal Dialysis
Authors: Tapawan Karen , Chen Elaine , Selk Natalie , Hong Edward , Virmani Sumeet , Balk Robert
Published: April 2011

Hydrothorax as a complication of peritoneal dialysis (PD) is a rare but recognized event. Proposed mechanisms for the development of a pleuro‐peritoneal communication include congenital diaphragmatic defects, acquired weakening of diaphragmatic fibers caused by high intra‐abdominal pressures during peritoneal dialysis, and impairments in lymphatic drainage. Pleural fluid analysis and diagnostic imaging assist in differentiation from other causes of pleural effusion. Nearly 50% of patients with this diagnosis have resolution of hydrothorax after temporary cessation of PD with interim hemodialysis for 2–6 weeks. Historically, other treatment options have included conventional pleurodesis and open thoracotomy with direct repair, producing variable results. With the advent of video‐assisted thoracoscopy (VATS), surgical repairs and pleurodesis are now frequently performed under direct visualization with minimal invasiveness. We report a case of hydrothorax in a patient after recent introduction to peritoneal dialysis. Pleuro‐peritoneal communication was documented with thoracentesis and radionuclide scanning. VATS pleurodesis with talc was performed. Repeat scintigraphy performed 1 week after the procedure revealed no residual communication, and patient was able to resume PD without further complications.
Performance and Risks of Open‐End Life Settlement Funds
Authors: Braun Alexander , Gatzert Nadine , Schmeiser Hato
Published: April 2011

Abstract

In this article, we comprehensively analyze open‐end funds dedicated to investing in U.S. senior life settlements. We begin by explaining their business model and the roles of institutions involved in the transactions of such funds. Next, we conduct the first empirical analysis of life settlement fund return distributions as well as a performance measurement, including a comparison to other asset classes. Since the funds contained in our data set cover a large fraction of this relatively young segment of the capital markets, representative conclusions can be derived. Even though the empirical results suggest that life settlement funds offer attractive returns paired with low volatility and are virtually uncorrelated with other asset classes, we find latent risk factors such as liquidity, longevity, and valuation risks. Since these risks did generally not materialize in the past and are hence largely not reflected by the historical data, they cannot be captured by classical performance measures. Thus, caution is advised in order not to overestimate the performance of this asset class.
Effects of pyriproxyfen on ovarian development and fecundity of Rhagoletis pomonella flies
Authors: Duan Jian Jun , Prokopy Ronald J. , Yin Chin‐Ming , Bergweiler Chris , Oouchi H.
Published: April 2011

Three‐day old female apple maggot flies, Rhagoletis pomonella (Walsh), were topically exposed to different doses (0.1, 1, 10, and 100 μg per fly) of a juvenile hormone mimic, pyriproxyfen, in the laboratory. Pyriproxyfen had little lethal effect on females except at the extremely high dose of 100 μg. It also had no significant effect on egg viability of treated females. A non‐lethal dose of 1 μg per fly did, however, enhance significantly the fecundity (egg production) as well as the ovarian development (number of eggs in ovaries and length of egg folicles) of treated flies. We conclude that pyriproxyfen could be a useful aid in exploring endocrine regulation of feeding and reproductive physiology behavior in R. pomonella, about which current knowledge is scant.
Ultrastructure of sensory receptors on the labium of the cassava mealybug, Phenacoccus manihoti Matile Ferrero
Authors: Le Rü B. , Renard Sophie , Allo Marie‐Rose , Le Lannic J. , Rolland J. P.
Published: April 2011

The ultrastructure of the sensory receptors located on the labium of the cassava mealybug Phenacoccus manihoti Matile‐Ferrero (Homoptera, Pseudococcidae) was studied with scanning and transmission electron microscopes. Trichoid hairs of probable mechanoreceptive function are distributed over the labium. Uniporous chemosensilla which possess a mechanoreceptive dendrite, multiporous chemosensilla and mechanoreceptive pegs are present on the tip of the labium. The presence of contact and olfactory chemoreceptors on the labial tip of P. manihoti suggests that tapping it on the cassava leaf provides the pest with information about the chemical nature of the leaf surface.
The interaction of surface and dust particle size on the pick‐up and grooming behaviour of the German cockroach Blattella germanica
Authors: El‐Awami I. O. , Dent D. R.
Published: April 2011

The relationship between the particle size of an inert silica dust, its up‐take from different surfaces and the grooming behaviour of males, gravid females, and fifth and sixth instar nymphs of the German cockroach Blattella germanica (Dictyoptera: Blattellidae) (L.) was investigated. The normal grooming behaviour of gravid females, nymphs and males differed according to sex and age. The gravid females and nymphs exhibited greater grooming activity than the males, especially of the antennae and the legs. Gravid females, nymphs, and adult males exhibited increased grooming activity after exposure to dust in the size range 0.5–63 μm, but there was no significant difference in grooming behaviour from the control when cockroaches were exposed to dust sizes greater than 70 μm. Antennal grooming by males was greater than leg grooming when exposed to all dust sizes, except size particles ranging 4.5–7.5 μm. A dust pick‐up experiment indicated that the average amount of dust transferred to B. germanica is affected by particle size, the porosity of the treated surface, and the sex and age of the cockroaches. Gravid females picked up greater amounts of dust than fifth and sixth instar nymphs, which in turn picked up more dust than males. Silica dust particles (0.5–7.5 μm) were picked up more effectively than larger particle sizes, by all three categories, males, females and fifth and sixth instar nymphs of cockroach on all three test surfaces plastic, ceramic and unpainted plywood. Plywood was the least effective surface for transfer of dust, of all sizes, to males, females and nymphs.
Marine omega‐3 fatty acids and mood disorders – linking the sea and the soul
Authors: Hegarty B. D. , Parker G. B.
Published: April 2011

Hegarty BD, Parker GB. Marine omega‐3 fatty acids and mood disorders – linking the sea and the soul.

Objective:  While there has long been interest in any nutritional contribution to the onset and treatment of mood disorders, there has been increasing scientific evaluation of several candidate nutritional and dietary factors in recent years. In this inaugural study of our ‘Food for Thought’ series, we will overview the evidence for any role of omega‐3 fatty acids (FA) in regulating mood.

Method:  Relevant literature was identified through online database searches and cross‐referencing.

Results:  Plausible mechanisms exist by which omega‐3 FA may influence neuronal function and mood. Cross‐sectional studies demonstrate an association between omega‐3 fatty acid deficiency and both depressive and bipolar disorders. Studies investigating the efficacy of omega‐3 fatty acid supplementation for mood disorders have however provided inconsistent results. The proportion of treatment studies showing a significant advantage of omega‐3 supplementation has dropped over the last 5 years. However, the vast heterogeneity of the trials in terms of constituent omega‐3 FAs, dose and length of treatment makes comparisons of these studies difficult.

Conclusion:  More research is required before omega‐3 supplementation can be firmly recommended as an effective treatment for mood disorders. Whereas increased omega‐3 FA intake may alleviate depressive symptoms, there is little evidence of any benefit for mania.
Infection, immunoregulation, and cancer
Authors: Rook Graham A. W. , Dalgleish Angus
Published: April 2011

Summary:  As man has moved rapidly from the hunter–gatherer environment to the living conditions of the industrialized countries, the incidences of some cancers have increased alarmingly. Recent increases are usually attributed to dietary changes or to altered exposures to putative carcinogens associated with the modern lifestyle. However, the changes in cancer incidence parallel similar increases in non‐neoplastic chronic inflammatory disorders (inflammatory bowel disease, allergies, and autoimmunity), and the epidemiology is often strikingly similar. This parallel is worth exploring, because the increases in chronic inflammatory disorders are at least partly explained by immunoregulatory defects resulting from diminished exposure to microorganisms that co‐evolved with mammals and developed a role in driving immunoregulatory circuits (the hygiene hypothesis). Dysregulated chronic inflammation can drive oncogenesis and also provides growth and angiogenic factors that enhance the subsequent proliferation and spread of tumor cells. Thus, a modern failure to downregulate inappropriate inflammation could underlie increases in some cancers in parallel with the increases in chronic inflammatory disorders. This possibility is supported by recent work showing that in some circumstances regulatory T cells protect against cancer, rather than aggravating it, as previously assumed. A greater understanding of these interactions might pave the way to improved microbe‐based immunotherapies.
A systems biological view of intracellular pathogens
Authors: Beiting Daniel P. , Roos David S.
Published: April 2011

Summary:  As biomedical research becomes increasingly data‐intensive, it is increasingly essential to integrate genomic‐scale datasets, so as to generate a more holistic picture of complex biological processes. The systems biology paradigm may differ in strategy from traditional reductionist scientific methods, but the goal remains the same: to generate tenable hypotheses driving the experimental elucidation of biological mechanisms. Intracellular pathogens provide an excellent opportunity for systems analysis, as many of these organisms are amenable to genetic manipulation, allowing their biology to be played off against that of the host. Moreover, many of the most fundamental biological properties of these microbes (host cell invasion, immune evasion, intracellular replication, long‐term persistence) are directly linked to pathogenesis and readily quantifiable using genomic‐scale technologies. In this review, we summarize and discuss some of the available and foreseeable functional genomics datasets pertaining to host–pathogen interactions and suggest that the host–pathogen interface represents a promising, tractable challenge for systems biological analysis. Success will require developing and leveraging new technologies, expanding data acquisition, and increasing public access to comprehensive datasets, to assemble quantitative and testable models of the host–pathogen relationship.
Control of central and peripheral tolerance by Aire
Authors: Metzger Todd C. , Anderson Mark S.
Published: April 2011

Summary:  The negative selection of self‐reactive thymocytes depends on the expression of tissue‐specific antigens by medullary thymic epithelial cells. The autoimmune regulator (Aire) protein plays an important role in turning on these antigens, and the absence of even one Aire‐induced tissue‐specific antigen in the thymus can lead to autoimmunity in the antigen‐expressing target organ. Recently, Aire protein has been detected in peripheral lymphoid organs, suggesting that peripheral Aire plays a complementary role here. In these peripheral sites, Aire was found to regulate the expression of a group of tissue‐specific antigens that is distinct from those expressed in the thymus. Furthermore, transgenic antigen expression in extrathymic Aire‐expressing cells (eTACs) can mediate deletional tolerance, but the immunological relevance of Aire‐dependent, endogenous tissue‐specific antigens remains to be determined.
Clinical tolerance in allogeneic hematopoietic stem cell transplantation
Authors: Roncarolo Maria‐Grazia , Gregori Silvia , Lucarelli Barbarella , Ciceri Fabio , Bacchetta Rosa
Published: April 2011

Summary:  Allogeneic hematopoietic stem cell transplantation (HSCT) has been a curative therapeutic option for a wide range of immune hematologic malignant and non‐malignant disorders including genetic diseases and inborn errors. Once in the host, allogeneic transplanted cells have not only to ensure myeloid repopulation and immunological reconstitution but also to acquire tolerance to host human leukocyte antigens via central or peripheral mechanisms. Peripheral tolerance after allogeneic HSCT depends on several regulatory mechanisms aimed at blocking alloimmune reactivity while preserving immune responses to pathogens and tumor antigens. Patients transplanted with HSCT represent an ideal model system in humans to identify and characterize the key cellular and molecular players underlying these mechanisms. The knowledge gained from these studies has allowed the development of novel therapeutic strategies aimed at inducing long‐term peripheral tolerance, which can be applicable not only in allogeneic HSCT but also in autoimmune diseases and solid‐organ transplantation. In the present review, we describe Type 1 regulatory T cells, initially discovered and characterized in chimeric patients transplanted with human leukocyte antigen‐mismatched HSCT, and how their presence correlates to tolerance induction and maintenance. Furthermore, we summarize different cell therapy approaches with regulatory T cells, designed to facilitate tolerance induction, minimizing pharmaceutical interventions.