bluuebunny/crossref_metadata_2025 huggingface dataset:
Aid, Economic Reform, and Public Sector Fiscal Behavior in Developing Countries
Authors: McGillivray Mark
Published: March 2009

This paper looks at interactions between foreign development aid, economic reform, and public sector fiscal behavior. It proposes a model of the public sector fiscal response to aid inflows, which allows for changes in structural relationships due to an exogenously imposed program of economic reform. This model is applied to 1960–99 time series data for the Philippines, which embarked on an IMF‐ and World Bank‐funded structural adjustment program in 1980. Estimates of structural and reduced‐form equations paint a dismal picture of the effectiveness of foreign aid to, and the structural adjustment program in, the Philippines so far as fiscal impacts are concerned. Both bilateral and multilateral aid inflows, and the presence of an economic reform program, are associated with decreases in public fixed capital expenditure, decreases in taxation and other recurrent revenue, and decreases in public sector saving. Multilateral aid also appears to be highly fungible.
Curbing Consumer Financial Losses: The Economics of Regulatory Enforcement
Authors: FAURE MICHAEL , OGUS ANTHONY , PHILIPSEN NIELS
Published: March 2009

This article deals with the question of how a high level of compliance with consumer protection legislation designed to prevent financial losses can be secured. We use a theoretical framework based on economic analysis of law to address some of the key policy options, such as proactive and reactive monitoring, providing officials with postdetection enforcement discretion, administrative, civil, and criminal sanctions, and facilitating actions by victims and third parties. On the basis of our theoretical framework and a classification of jurisdictions into different groups (models of enforcement policy), we identify some key elements of an enforcement regime and indicate in what circumstances a particular solution can be expected to be more or less cost effective.
Beware of ‘Good’ Outliers and Overoptimistic Conclusions*
Authors: Dehon Catherine , Gassner Marjorie , Verardi Vincenzo
Published: March 2009

The main goal of this paper is to warn practitioners of the danger of neglecting outliers in regression analysis, in particular, good leverage points (i.e. points lying close to the regression hyperplane but outlying in the x‐dimension). While the types of outliers which do influence regression estimates (vertical outliers and bad leverage points) have been extensively investigated, good leverage points have been largely ignored, probably because they do not affect the estimated regression parameters. However, their effect on inference is far from negligible. We propose a step‐by‐step procedure to identify and treat all types of outliers. The paper of Persson and Tabellini [American Economic Review (2004) Vol. 94, pp. 25–46] linking the degree of proportionality of an electoral system to the size of government is discussed to illustrate how the choice of a measure and the existence of atypical observations may substantially influence results.
Combining Forecasts from Nested Models*
Authors: Clark Todd E. , McCracken Michael W.
Published: March 2009

Motivated by the common finding that linear autoregressive models often forecast better than models that incorporate additional information, this paper presents analytical, Monte Carlo and empirical evidence on the effectiveness of combining forecasts from nested models. In our analytics, the unrestricted model is true, but a subset of the coefficients is treated as being local‐to‐zero. This approach captures the practical reality that the predictive content of variables of interest is often low. We derive mean square error‐minimizing weights for combining the restricted and unrestricted forecasts. Monte Carlo and empirical analyses verify the practical effectiveness of our combination approach.
Assessing priority areas by imperilled species: insights from the European butterflies
Authors: Fattorini S.
Published: March 2009

Biodiversity hotspots have been variously defined in terms of species richness, endemic species or imperilled species. The use of imperilled species to locate priority areas is particularly problematic, because an area that hosts a large number of imperilled species is likely to be under severe threats, making less effective conservation efforts. A possibly way to answer this problem is to assess species threats at two spatial scales. Then, areas which host concentrations of species that are imperilled at the larger scale, but not at the smaller scale, can be considered as priority areas where conservation efforts are expected to be more effective. An application of this procedure to the European butterfly fauna with the Biodiversity Conservation Concern index calculated with two IUCN red listings (European and national) allowed the construction of a four‐celled model that reflects different types of conservation priority. This combined use of international and regional red lists may be a tool to make practical decisions (e.g. allocation of funds or legislative actions) to preserve imperilled species.
Male infertility, female fertility and extrapair copulations
Authors: Hasson Oren , Stone Lewi
Published: March 2009

Females that are socially bonded to a single male, either in a social monogamy or in a social polygyny, are often sexually polyandrous. Extrapair copulations (EPC) have often been suggested or rejected, on both empirical and theoretical grounds, as an important mechanism that enables females to avoid fertility risks in case their socially bonded male is infertile. Here, we explore this possibility in two steps. First, we present a mathematical model that assumes that females have no precopulatory information about male fertility, and shows that a female EPC strategy increases female reproductive success only if certain specific conditions are upheld in the nature of male infertility. In particular, these conditions require both (i) that fertile sperm precedence (FSP) is absent or incomplete within ejaculates of the same male (i.e. that an infertile male is, at least partly, truly infertile), and (ii) the existence of FSP among ejaculates of different males (such that infertile spermatozoa of the infertile male are at a disadvantage when competing against spermatozoa of a fertile male). Second, to evaluate their potential role in the evolution of female EPC, we review the abundance and FSP patterns of the different male infertility types. The conclusion is drawn that some common infertility types, such as poor sperm count or motility, contribute to the evolution of female EPC, whereas other common infertility types, such as sperm depletion or allocation in a social monogamy (but not in a social polygyny), and in particular male driven polyspermy, do not. Also, a deeper look at the arms race between sperm fertilization efficiency and female barriers to sperm may answer the non‐trivial question: “why are some types of infertility so common?”
To what extent did Neanderthals and modern humans interact?
Authors: Herrera Kristian J. , Somarelli Jason A. , Lowery Robert K. , Herrera Rene J.
Published: March 2009

Neanderthals represent an extinct hominid lineage that existed in Europe and Asia for nearly 400,000 years. They thrived in these regions for much of this time, but declined in numbers and went extinct around 30,000 years ago. Interestingly, their disappearance occurred subsequent to the arrival of modern humans into these areas, which has prompted some to argue that Neanderthals were displaced by better suited and more adaptable modern humans. Still others have postulated that Neanderthals were assimilated into the gene pool of modern humans by admixture. Until relatively recently, conclusions about the relationships between Neanderthals and contemporary humans were based solely upon evidence left behind in the fossil and archaeological records. However, in the last decade, we have witnessed the introduction of metagenomic analyses, which have provided novel tools with which to study the levels of genetic interactions between this fascinating Homo lineage and modern humans. Were Neanderthals replaced by contemporary humans through dramatic extinction resulting from competition and/or hostility or through admixture? Were Neanderthals and modern humans two independent, genetically unique species or were they a single species, capable of producing fertile offspring? Here, we review the current anthropological, archaeological and genetic data, which shed some light on these questions and provide insight into the exact nature of the relationships between these two groups of humans.
Phenylacetic acids and the structurally related non‐steroidal anti‐inflammatory drug diclofenac bind to specific γ‐hydroxybutyric acid sites in rat brain
Authors: Wellendorph Petrine , Høg Signe , Skonberg Christian , Bräuner‐Osborne Hans
Published: March 2009

γ‐Hydroxybutyric acid (GHB) is a proposed neurotransmitter or neuromodulator with a yet unresolved mechanism of action. GHB binds to both specific high‐affinity GHB binding sites and to γ‐aminobutyric acid subtype B (GABAB) receptors in the brain. To separate specific GHB effects from GABABreceptor effects, it is imperative to develop GHB selective and potent compounds. We generated the compound, 4‐(biphen‐4‐yl)‐4‐hydroxybutyric acid, which is the 4‐hydroxyl analogue of the non‐steroidal anti‐inflammatory drug (NSAID) fenbufen (referred to as γ‐hydroxyfenbufen). When measured in a rat brain homogenate [3H]NCS‐382 binding assay, γ‐hydroxyfenbufen inhibited [3H]NCS‐382 binding with a 10‐fold higher affinity than GHB (Ki0.44 μm), thus establishing it as a novel lead structure. The active metabolite of fenbufen, 4‐biphenylacetic acid inhibited [3H]NCS‐382 binding with a twofold higher affinity than GHB. Measuring the affinities of structurally related NSAIDs for the [3H]NCS‐382 site identified diclofenac, a clinically relevant NSAID (Voltaren®, Diclon®) of the phenylacetic acid (PAA) type, as a GHB ligand (Kivalue of 5.1 μm). Other non‐NSAID PAAs also exhibited affinities similar to GHB. Our data raise the interesting possibility that the widely used over‐the‐counter drug compound, diclofenac, might affect GHB binding at relevant clinical dosages. Furthermore, the identification of PAAs as GHB ligands supplies new information about the structural preferences of the GHB ligand‐binding site.
A NEW LATE CRETACEOUS MACROSEMIID FISH (NEOPTERYGII, HALECOSTOMI) FROM MOROCCO, WITH TEMPORAL AND GEOGRAPHICAL RANGE EXTENSIONS FOR THE FAMILY
Authors: MURRAY ALISON M. , WILSON MARK V. H.
Published: March 2009

Abstract:  A recent collection of actinopterygian fossil fishes from a previously unreported locality in the Cenomanian or Turonian of southeastern Morocco includes a single specimen of a macrosemiid fish. Macrosemiids are more common in Jurassic and Early Cretaceous deposits, with the previously known range of the family being Late Triassic through Aptian or Albian. This discovery therefore extends the temporal range of the family into the Late Cretaceous. Moreover, macrosemiids had not previously been reported from northern Africa or the Moroccan area of the Tethys basin; therefore, this fossil also increases the geographical range of the family. The Moroccan macrosemiid is described in a new genus and species, Agoultichthys chattertoni. A phylogenetic analysis places it basal to all other genera of the family with the exception of Notagogus. Diagnostic characters of the new species include the high number of scales laterally along the body and the greater number of dorsal fin rays than in other members of the family.
GUODUNITES, A LOW‐PALAEOLATITUDE AND TRANS‐PANTHALASSIC SMITHIAN (EARLY TRIASSIC) AMMONOID GENUS
Authors: BRAYARD ARNAUD , BRÜHWILER THOMAS , BUCHER HUGO , JENKS JIM
Published: March 2009

Abstract:  Based on new, bed‐rock controlled material from Oman and Utah, USA, the Early Triassic genus Guodunites, which was recently erected on the basis of scarce specimens from northwestern Guangxi, South China, is now shown to be a representative of Proptychitidae. This solves the question of the previously unknown phylogenetic affinity of this genus. The genus is restricted to the late middle Smithian, and to date, its biogeographical distribution comprises Oman, South China and Utah, thus indicating an essentially low palaeolatitudinal distribution during the Early Triassic. Its palaeobiogeographical distribution further strengthens the existence of significant equatorial faunal exchanges between both sides of the Panthalassa at that time. It also suggests that, in addition to the potential stepping stones represented by Panthalassic terranes, vigorous equatorial oceanic currents must have contributed largely to the dispersal of ammonoids during such time intervals.
Effects of Survey Mode, Patient Mix, and Nonresponse on CAHPS® Hospital Survey Scores
Authors: Elliott Marc N. , Zaslavsky Alan M. , Goldstein Elizabeth , Lehrman William , Hambarsoomians Katrin , Beckett Megan K. , Giordano Laura
Published: March 2009

Objective. To evaluate the need for survey mode adjustments to hospital care evaluations by discharged inpatients and develop the appropriate adjustments.

Data Source. A total of 7,555 respondents from a 2006 national random sample of 45 hospitals who completed the CAHPS® Hospital (HCAHPS [Hospital Consumer Assessments of Healthcare Providers and Systems]) Survey.

Study Design/Data Collection/Extraction Methods. We estimated mode effects in linear models that predicted each HCAHPS outcome from hospital‐fixed effects and patient‐mix adjustors.

Principal Findings. Patients randomized to the telephone and active interactive voice response (IVR) modes provided more positive evaluations than patients randomized to mail and mixed (mail with telephone follow‐up) modes, with some effects equivalent to more than 30 percentile points in hospital rankings. Mode effects are consistent across hospitals and are generally larger than total patient‐mix effects. Patient‐mix adjustment accounts for any nonresponse bias that could have been addressed through weighting.

Conclusions. Valid comparisons of hospital performance require that reported hospital scores be adjusted for survey mode and patient mix.
From Catholic Milieu to Lived Religion: The Social and Cultural History of Modern German Catholicism1
Authors: O'Sullivan Michael E.
Published: March 2009

The ‘milieu’ concept, first introduced to German history during the 1960s, experienced a revival during the last twenty years. It became especially influential as a model for modern German Catholic social history. Scholarship based on this notion of an insular religious subculture deserves much praise for its analysis of how Catholics remained relevant as a minority in a modernizing country and for shedding new light on the relationship between Catholicism and National Socialism. However, future work on the Catholic community in Germany requires greater methodological flexibility. The purposes of this article are to review the recent historiography of the German Catholic milieu after World War I, discuss existing critiques of this literature, and suggest ways to better integrate cultural and gender history into narratives about twentieth‐century German Catholicism.
Recent Research on the Andes before Independence: Ethnohistory, Social History, and Revolt and Revolution
Authors: Ramírez Susan Elizabeth
Published: March 2009

Over the last few decades, scholars of the Andes have peopled the institutions studied and defined by previous generations of investigators. The resulting scholarship shows the sometimes stark contrast between legal theory and practice through the re‐telling of incidents and anecdotes and the analysis of the collective biographies of Spanish colonists, native peasants, blacks, and mixed‐bloods (thecastas). This overview will highlight the contributions of recent research on native societies, social history, and the mounting instability that characterized the eighteenth century.
SCN1A duplications and deletions detected in Dravet syndrome: Implications for molecular diagnosis
Authors: Marini Carla , Scheffer Ingrid E. , Nabbout Rima , Mei Davide , Cox Kathy , Dibbens Leanne M. , McMahon Jacinta M. , Iona Xenia , Carpintero Rochio Sanchez , Elia Maurizio , Cilio Maria Roberta , Specchio Nicola , Giordano Lucio , Striano Pasquale , Gennaro Elena , Cross J. Helen , Kivity Sara , Neufeld Miriam Y. , Afawi Zaid , Andermann Eva , Keene Daniel , Dulac Olivier , Zara Federico , Berkovic Samuel F. , Guerrini Renzo , Mulley John C.
Published: March 2009

Objective:  We aimed to determine the type, frequency, and size of microchromosomal copy number variations (CNVs) affecting the neuronal sodium channel α 1 subunit gene (SCN1A) in Dravet syndrome (DS), other epileptic encephalopathies, and generalized epilepsy with febrile seizures plus (GEFS+).

Methods:  Multiplex ligation‐dependent probe amplification (MLPA) was applied to detect SCN1A CNVs among 289 cases (126 DS, 97 GEFS+, and 66 with other phenotypes). CNVs extending beyond SCN1A were further characterized by comparative genome hybridization (array CGH).

Results:  Novel SCN1A CNVs were found in 12.5% of DS patients where sequence‐based mutations had been excluded. We identified the first partial SCN1A duplications in two siblings with typical DS and in a patient with early‐onset symptomatic generalized epilepsy. In addition, a patient with DS had a partial SCN1A amplification of 5–6 copies. The remaining CNVs abnormalities were four partial and nine whole SCN1A deletions involving contiguous genes. Two CNVs (a partial SCN1A deletion and a duplication) were inherited from a parent, in whom there was mosaicism. Array CGH showed intragenic deletions of 90 kb and larger, with the largest of 9.3 Mb deleting 49 contiguous genes and extending beyond SCN1A.

Discussion:  Duplication and amplification involving SCN1A are now added to molecular mechanisms of DS patients. Our findings showed that 12.5% of DS patients who are mutation negative have MLPA‐detected SCN1A CNVs with an overall frequency of about 2–3%. MLPA is the established second‐line testing strategy to reliably detect all CNVs of SCN1A from the megabase range down to one exon. Large CNVs extending outside SCN1A and involving contiguous genes can be precisely characterized by array CGH.
Uncertainty Analysis Based on Probability Bounds (P‐Box) Approach in Probabilistic Safety Assessment
Authors: Karanki Durga Rao , Kushwaha Hari Shankar , Verma Ajit Kumar , Ajit Srividya
Published: March 2009

A wide range of uncertainties will be introduced inevitably during the process of performing a safety assessment of engineering systems. The impact of all these uncertainties must be addressed if the analysis is to serve as a tool in the decision‐making process. Uncertainties present in the components (input parameters of model or basic events) of model output are propagated to quantify its impact in the final results. There are several methods available in the literature, namely, method of moments, discrete probability analysis, Monte Carlo simulation, fuzzy arithmetic, and Dempster‐Shafer theory. All the methods are different in terms of characterizing at the component level and also in propagating to the system level. All these methods have different desirable and undesirable features, making them more or less useful in different situations. In the probabilistic framework, which is most widely used, probability distribution is used to characterize uncertainty. However, in situations in which one cannot specify (1) parameter values for input distributions, (2) precise probability distributions (shape), and (3) dependencies between input parameters, these methods have limitations and are found to be not effective. In order to address some of these limitations, the article presents uncertainty analysis in the context of level‐1 probabilistic safety assessment (PSA) based on a probability bounds (PB) approach. PB analysis combines probability theory and interval arithmetic to produce probability boxes (p‐boxes), structures that allow the comprehensive propagation through calculation in a rigorous way. A practical case study is also carried out with the developed code based on the PB approach and compared with the two‐phase Monte Carlo simulation results.
Punishment and Beyond: Achieving Justice Through the Satisfaction of Multiple Goals
Authors: Gromet Dena M. , Darley John M.
Published: March 2009

We investigated the hypothesis that people's need for punishment does not preclude a desire for restorative sanctions that address the repairing of the harm to victims and communities caused by wrongdoing. Study 1 showed that although people felt it was important to punish the offender to achieve justice, they viewed additional justice goals as equally necessary. Study 2 revealed that people viewed sanctions as differentially able to fulfill various justice goals. Study 3 showed that the target on which respondents focused—the offender, victim, or community—determined which sanctions they selected to achieve justice; and that people did tend, by default, to focus on punishing the offender when responding to crime. These findings, taken together, suggest that people view the satisfaction of multiple justice goals as an appropriate and just response to wrongdoing, which allows for a possible reconciliation between the “conflicting” goals of restorative and retributive justice.
On the Edge of the Law: Women's Property Rights and Dispute Resolution in Kisii, Kenya
Authors: Henrysson Elin , Joireman Sandra F.
Published: March 2009

Scholars have argued that economic efficiency requires a clear definition of the rights of ownership, contract, and transfer of land. Ambiguity in the definition or enforcement of any of these rights leads to an increase in transaction costs in the exchange and transfer of land as well as a residual uncertainty after any land contract. In Kenya, government efforts at establishing clearly defined property rights and adjudication mechanisms have been plagued by the existence of alternative processes for the adjudication of disputes. Customary dispute resolution has been praised as an inexpensive alternative to official judicial processes in a legally pluralistic environment. However, our research demonstrates that customary processes may also carry a monetary cost that puts them beyond the means of many citizens. This article compares the costs and processes of the formal and informal methods of property rights adjudication for women in the Kisii region of Kenya. The research results suggest that women have weak property rights overall, they have limited access to formal dispute resolution systems because of costs involved, and even the informal systems of conflict resolution are beyond the means of many citizens.
Landscapes of the Law: Injury, Remedy, and Social Change in Thailand
Authors: Engel David M.
Published: March 2009

Sociolegal theorists since Weber have postulated that state law operates by interacting with and responding to nonstate legal orders. This article, examining conceptions of injury and compensation in Thailand, analyzes two ways of mapping law onto the landscape. The first is associated with state law and legal institutions established at the turn of the twentieth century. The state legal system imagines space from the outside in, drawing a boundary line and applying law uniformly throughout the jurisdiction it has enclosed. A second type of mapping, which has been more familiar over the centuries to ordinary Thai people, imagines space from the inside out. Nonstate legal orders are associated with sacred centers and radiate outward, diminishing in intensity and effectiveness with distance. This article, based on extensive interviews with injured persons and other actors and observers in northern Thailand, examines the interconnections between these two ways of imagining the landscape of law. It suggests that recent transformations of Thai society have rendered ineffective the norms and procedures associated with the law of sacred centers. Consequently, state law no longer interacts with or responds to nonstate law and surprisingly plays a diminished role in the lives of ordinary people who suffer injuries.
The Shared History: Unknotting Fictive Kinship and Legal Process
Authors: Jacob Marie-Andrée
Published: March 2009

This article looks in detail at a form of kinship that is contingently crafted and mobilized to achieve specific purposes. On the basis of ethnographic material collected among local actors within bodies that regulate kidney transplants in Israel, the objective of this article is to expand the sociolegal definition of fictive kinship. I usetransplant relatednessto refer to the set of formal and informal norms that grow out of social and medico-legal practices in the field of kidney donations and sales; however, the form of fictive kinship that appears in this specific field tells us something broader about kinship as it is constructed and performed in legal processes more generally. The configuration of fictive kinship that is examined is the shared history (historia meshoutefet). I argue that in the present case, the shared history alters social and legal deep-seated understandings of kinship and ultimately makes the distinctions between allegedly real and pseudo-kinship collapse.
Gene expression profiles of BMP4, FGF10 and cognate inhibitors, in the skin of foetal Merino sheep, at the time of secondary follicle branching
Authors: Menzies Moira , Stockwell Sally , Brownlee Alan , Cam Graham , Ingham Aaron
Published: March 2009

Abstract:  The high concentration of secondary branched follicles is a distinctive feature of the Merino sheep. These follicles initiate from 100 days of gestation. Here, we report a transition in abundance of the BMP4 and FGF10 morphogens occurring at this time. At 103 days of gestation, FGF10 gene expression dropped steadily from maximal levels, in a trend that continued until day 143. Conversely, from day 105, BMP4 transcript levels rapidly increased to maximal levels that were maintained until 131 days, before declining. This profile closely matches reported changes in branched follicle numbers, which peak in density at day 134. SPRY4, a known regulator of FGF10, increased to maximal levels concomitant with the fall in FGF10, suggesting a relationship. Levels of the BMP4 inhibitor NOG matched the initial rise of BMP4, with a fivefold spike at 108 days; but consistent with the rise in BMP4, this high level was not sustained.
Opioids and the skin – where do we stand?
Authors: Bigliardi Paul L. , Tobin Desmond J. , Gaveriaux‐Ruff Claire , Bigliardi‐Qi Mei
Published: March 2009

Abstract: The common ectodermal origin of the skin and nervous systems can be expected to predict likely interactions in the adult. Over the last couple of decades much progress has been made to elucidate the nature of these interactions, which provide multidirectional controls between the centrally located brain and the peripherally located skin and immune system. The opioid system is an excellent example of such an interaction and there is growing evidence that opioid receptors (OR) and their endogenous opioid agonists are functional in different skin structures, including peripheral nerve fibres, keratinocytes, melanocytes, hair follicles and immune cells. Greater knowledge of these skin‐associated opioid interactions will be important for the treatment of chronic and acute pain and pruritus. Topical treatment of the skin with opioid ligands is particularly attractive as they are active with few side effects, especially if they cannot cross the blood–brain barrier. Moreover, cutaneous activation of the opioid system (e.g. by peripheral nerves, cutaneous and immune cells, especially in inflamed and damaged skin) can influence cell differentiation and apoptosis, and thus may be important for the repair of damaged skin. While many of the pieces of this intriguing puzzle remain to be found, we attempt in this review to weave a thread around available data to discuss how the peripheral opioid system may impact on different key players in skin physiology and pathology.
Expressions of rod and cone photoreceptor‐like proteins in human epidermis
Authors: Tsutsumi Moe , Ikeyama Kazuyuki , Denda Sumiko , Nakanishi Jotaro , Fuziwara Shigeyoshi , Aoki Hirofumi , Denda Mitsuhiro
Published: March 2009

Abstract:  Previous reports have suggested the existence of photoreceptors for visible radiation at the surface of the human body. Rhodopsin is a well‐known photosensitive protein found in the rod cells of the retina and detects light/dark contrast. Cone opsins are also photosensitive receptors in the cone cells of the retina and detect colour. Here, we describe immunochemical studies using anti‐rhodopsin and anti‐opsin antibodies on human skin. Both mouse retina and human epidermis showed clear immunoreactivity with each antibody. Interestingly, immunoreactivity against longer‐wavelength opsin antibody was observed in the basal layer of the epidermis, while immunoreactivity against rhodopsin and shorter‐wavelength opsin was observed in the upper layer. PCR analysis confirmed the expression of rhodopsin‐like and opsin‐like genes in human retina and the skin. These results suggest that a series of proteins, which play a crucial role in visual perception, are expressed in human epidermis.
Pharmacogenomics in dermatology: from susceptibility genes to personalized therapy
Authors: Pincelli Carlo , Pignatti Marco , Borroni Riccardo G.
Published: March 2009

Abstract:  A significant proportion of patients with skin disease do not respond to treatment and adverse drug reactions are a common problem. Genetic factors are important determinants for both drug efficacy and toxicity. The fields of pharmacogenetics and pharmacogenomics examine inter‐individual variations in the DNA sequence that are related to drug efficacy and toxicity. Here, we present pharmacogenomic data relevant to dermatology and explore the role of dermatologists in identifying patients who may respond to treatment or experience adverse drug reactions.
The multiple faces of nicotine and its implications in tissue and wound repair
Authors: Martin John W. , Mousa Shaymaa S. , Shaker Olfat , Mousa Shaker A.
Published: March 2009

Abstract: Nicotine, one of the thousands of chemicals in cigarette smoke has a highly debated effect on cell proliferation and tissue healing. Recent studies documented its pro‐angiogenesis effects by stimulating endothelial cell α7‐non‐neronal nicotinic acetyl choline receptors (α7 N‐nACHR). It is well known that individuals who smoke or have diabetes experience impaired wound healing although for different reasons. This review evaluates several current studies relating to nicotine’s ability to mediate cellular activation, migration and angiogenesis in attempts to correlate these data with nicotine’s ability to repair wounds in ischaemic tissue. While its beneficial effects are still under investigation, important findings regarding nicotine’s acceleration of atherosclerosis, tumor angiogenesis, cell proliferation e and resistance to apoptosis put its systemic use into question. Based on the good and bad sides of nicotine, it is recommended to restrict its utility to local applications.
New insights into the mechanisms of polymorphic light eruption: resistance to ultraviolet radiation‐induced immune suppression as an aetiological factor
Authors: Wolf Peter , Byrne Scott N. , Gruber‐Wackernagel Alexandra
Published: March 2009

Abstract:  An abnormal immune response has long been thought responsible for the patho‐aetiology of polymorphic light eruption, the most common photodermatosis. Recent evidence indicates that polymorphic light eruption patients are resistant to the immune suppressive effects of sunlight, a phenomenon that leads to the formation of skin lesions upon seasonal sun exposure. This immunological abnormality in polymorphic light eruption supports the concept of the biological significance and evolutionary logic of sunlight‐induced immune suppression, i.e. the prevention of immune responses to photo‐induced neo‐antigens in the skin, thereby preventing autoimmunity and skin rashes. This article focuses on the immunological alterations in polymorphic light eruption and the pathogenic significance to the disease state and skin carcinogenesis.
Inhibition of Rac1 GTPase downregulates vascular endothelial growth factor receptor‐2 expression by suppressing Sp1‐dependent DNA binding in human endothelial cells
Authors: Meissner Markus , Michailidou Despina , Stein Monika , Hrgovic Igor , Kaufmann Roland , Gille Jens
Published: March 2009

Abstract:  RhoA, Rac1 and CDC42 are small GTP‐binding proteins of the Rho family that play a crucial role in regulation of the actin‐based cytoskeleton. In addition to cell growth regulation, they are implicated in transcriptional activation, oncogenic transformation and angiogenesis. The small Rho‐GTPases have been linked to vascular endothelial growth factor (VEGF)‐induced signalling pathways, but their role has not yet been elucidated. As signalling via the VEGF receptor‐2 (VEGFR2) pathway is critical for angiogenic responses in cancer, wound repair and ischaemic and inflammatory diseases, we investigated whether the small Rho‐GTPase Rac1 influences VEGFR2 expression in human endothelial cells. In this study, we show that a dominant negative Rac1 expression vector led to a pronounced decrease in VEGFR2 mRNA and protein expression. To identify minimal promoter requirements and potential applications of the small Rho‐GTPases, we used VEGFR2 promoter–reporter gene constructs containing various deletions. The inhibitory effects of dominant negative Rac1 on the transcriptional activity of the VEGFR2 promoter localized to an element between −77 and −60 that contains an Sp1 transcription factor binding site. Electrophoretic mobility shift assays demonstrated that constitutive Sp1‐dependent DNA binding decreased with Rac1 inhibition. Hence, repression of the small Rho GTPase Rac1 seems to be an additional critical molecular mechanism in the regulation of VEGFR2 expression.
High‐risk pregnancy in rhesus monkeys (Macaca mulatta): a case of ectopic, abdominal pregnancy with birth of a live, term infant, and a case of gestational diabetes complicated by pre‐eclampsia
Authors: Krugner‐Higby Lisa , Luck Melissa , Hartley Deborah , Crispen Heather M. , Lubach Gabriele R. , Coe Christopher L.
Published: March 2009

Background  Cases of abdominal pregnancy, in the form of intra‐abdominal mummified fetuses, have been described in nonhuman primates. Gestational diabetes and pre‐eclampsia are common pregnancy complications in women.

Methods  Two timed‐bred rhesus monkeys had high‐risk pregnancies, an abdominal pregnancy with delivery of a live term infant, and a case of gestational diabetes that later developed pre‐eclampsia.

Results  The monkey that had abdominal pregnancy later died from septic peritonitis. The monkey had a colonic adenocarcinoma that may have allowed leakage of intestinal contents into the abdomen. Her infant was fostered to another female and survived. The monkey with gestational diabetes and pre‐eclampsia was treated with a regimen similar to that used in women, and a live infant was delivered at day 157 of gestation by Caesarian section.

Conclusion  These cases underscore the value of timed‐breeding and the similarities between pregnancy complications in women and in nonhuman primates.
Delivery of a classical antihypertensive agent through the skin by chemical enhancers and iontophoresis
Authors: Nair Anroop , Reddy Chandrasekhar , Jacob Shery
Published: March 2009

Background/purpose: Oral therapy with antihypertensive agents is generally associated with severe GI side effects and low patient compliance. Therefore, development of a method of drug delivery that maintains the proper drug level for a prolonged period without adverse effects is required. Thus, transdermal delivery has all the necessities that are required for delivery of classical antihypertensive agents. However, the different approaches to enhance the transport of atenolol through intact skin have not resulted in a remarkable improvement.

Methods: The effect of the drug concentration and a binary system (water–ethanol) on the atenolol flux was investigated. Further, the effects of chemical enhancers (menthol, oleic acid, polyethylene glycol 400, sodium lauryl sulphate, di methyl formamide and N‐methyl‐2‐pyrrolidone) at different concentrations and their combined effects with iontophoresis were examined.

Results: Among the binary systems, the highest flux was obtained when 75% v/v ethanol in water was used. Atenolol flux enhanced significantly (P<0.001) at the 5% w/v concentration among all the enhancers studied. It was also observed that the combination of iontophoresis with oleic acid (5% w/v) showed the maximum benefit with a steady‐state flux of 2.66 μmol/cm2/h.

Conclusion: The combination of iontophoresis with permeation enhancers was found to be promising in delivering atenolol across the skin, and the highest permeation was attained when oleic acid was combined with iontophoresis. The in vitro flux value obtained (when oleic acid combined with iontophoresis) was 0.71 mg/cm2/h, which points to the fact that a therapeutically effective concentration can be attained with 1.2 cm2 of skin contact area.
The evaluation of whitening efficacy of cosmetic products using a human skin pigmentation spot model
Authors: Tian Y. , Hoshino T. , Chen C. J. , E Y. , Yabe S. , Liu W.
Published: March 2009

Background: To establish a pigmentation spot model on human skin and to assess whitening efficacy for whitening products by this established pigmentation spot model.

Methods: Twenty subjects between 20 and 45 years old with skin phototype III or IV were selected. Three consecutive daily UV exposures were performed on buttocks of the subjects as follows: Day 1=1 minimal erythema dose (MED), Day 2=0.5 MED and Day 3=0.5 MED. After the first UV exposure, a selected whitening product was applied to the subjects twice a day on UV exposure area. The application of the whitening product to subjects on the exposed areas was continued till Day 27. CM2500d chromameter, Maxmeter MX18 and visual evaluation were used to assess changes of skin color.

Results: A pigmentation spot model after UV exposure was established. The measurement of the pigment spot showed that value declined abruptly at Day 3 and then slowly reached to a lowest point at Day 6. value of the pigment spot almost remained at the same level until Day 20, thereafter increased slowly. The value showed an abrupt increase at Day 3 and slowly reached to a maximal level at Day 6. The value slowly declined toward its baseline level. Likewise, the erythema index also increased significantly at Day 3, and reached to a maximal level at Day 6 and then slowly declined. However, , and erythema indices did not return to their baseline levels during the 27‐day period of this study. On the other hand, value started to increase from Day 3 and such increase was observed continuously to Day 27. Melanin index also showed a slow increase during the first 3 days. It started to increase rapidly from Day 3 and a to maximal level at Day 9 and maintain at a plateau till Day 27 (with an exception at Day 13). To assess the whitening product by this pigmentation spot model, ΔL, , and ΔM values were analyzed. It showed that absolute ΔL value and value of whitening products were lower than those values of the vehicle of the whitening product at each checkpoint, while ΔM value of the whitening product was lower only at Day 9 and Day 20, although no statistically significant differences was found. The visual results also strongly supported that the whitening product enhanced the decrease of pigmentation.

Conclusion: This study showed that repeated UV exposure was able to induce a long extensive period of pigment formation. The resulted pigmentation spot was able to maintain at an elevated level till Day 20. Clinical subjective evaluations together with combined objective instrument measurements were still important to assess whitening and spot‐removing ability of a material due to the instrument limitation for color differentiations. This kind of pigmentation spot model can be used to assess whitening efficacy for whitening or spot‐removing products. In addition, the combinations of subjective and objective methods were able to serve as advisable references to assess the whitening efficacy of products.
The facial red fluorescence of ultraviolet photography: is this color due to Propionibacterium acnes or the unknown content of secreted sebum?
Authors: Youn Sang Woong , Kim Jun Hyung , Lee Jai Eun , Kim Sun Ok , Park Kyoung Chan
Published: March 2009

Background/purpose: Red fluorescence of the face induced by ultraviolet light is thought to be due to Propionibacterium acnes. However, recently there are reports correlating this red fluorescence with the amount of facial sebum secretion. This study was performed to investigate the relationship between the areas of facial red fluorescence with culture results of P. acnes and the amount of sebum secretion.

Methods: Nineteen patients with acne were included. P. acnes cultures were done on specimens obtained from areas with red fluorescence. In addition, the amount of facial sebum secretion and the skin surface pH (SSPH) were measured. Correlation analysis of these parameters and the culture results were performed with the image analysis data from the red fluorescence of the face.

Results: P. acnes was cultured in 36.5% of cases. The correlation of the culture rate with the red fluorescence areas was not significant. After classifying the patients into high‐sebum and low‐sebum groups, there was a significant difference in the red fluorescence areas. In addition, the red fluorescence area correlated with the SSPH.

Conclusions: The red fluorescence area showed a stronger correlation with sebum secretion than with the presence of P. acnes. This finding suggests that the red fluorescence is affected by sebum not just P. acnes.
Novel type III polyketide synthases from Aloe arborescens
Authors: Mizuuchi Yuusuke , Shi She‐Po , Wanibuchi Kiyofumi , Kojima Akiko , Morita Hiroyuki , Noguchi Hiroshi , Abe Ikuro
Published: March 2009

Aloe arborescens is a medicinal plant rich in aromatic polyketides, such as pharmaceutically important aloenin (hexaketide), aloesin (heptaketide) and barbaloin (octaketide). Three novel type III polyketide synthases (PKS3, PKS4 and PKS5) were cloned and sequenced from the aloe plant by cDNA library screening. The enzymes share 85–96% amino acid sequence identity with the previously reported pentaketide chromone synthase and octaketide synthase. Recombinant PKS4 and PKS5 expressed in Escherichia coli were functionally identical to octaketide synthase, catalyzing the sequential condensations of eight molecules of malonyl‐CoA to produce octaketides SEK4/SEK4b. As in the case of octaketide synthase, the enzymes are possibly involved in the biosynthesis of the octaketide barbaloin. On the other hand, PKS3 is a multifunctional enzyme that produces a heptaketide aloesone (i.e. the aglycone of aloesin) as a major product from seven molecules of malonyl‐CoA. In addition, PKS3 also afforded a hexaketide pyrone (i.e. the precursor of aloenin), a heptaketide 6‐(2‐acetyl‐3,5‐dihydroxybenzyl)‐4‐hydroxy‐2‐pyrone, a novel heptaketide 6‐(2‐(2,4‐dihydroxy‐6‐methylphenyl)‐2‐oxoethyl)‐4‐hydroxy‐2‐pyrone and octaketides SEK4/SEK4b. This is the first demonstration of the enzymatic formation of the precursors of the pharmaceutically important aloesin and aloenin by a wild‐type PKS obtained from A. arborescens. Interestingly, the aloesone‐forming activity was maximum at 50 °C, and the novel heptaketide pyrone was non‐enzymatically converted to aloesone. In PKS3, the active‐site residue 207, which is crucial for controlling the polyketide chain length depending on the steric bulk of the side chain, is uniquely substituted with Ala. Site‐directed mutagenesis demonstrated that the A207G mutant dominantly produced the octaketides SEK4/SEK4b, whereas the A207M mutant yielded a pentaketide 5,7‐dihydroxy‐2‐methylchromone.
Family‐Identified Barriers to Medication Reconciliation
Authors: Riley‐Lawless Kathy
Published: March 2009

PURPOSE.  This study aims to discover family‐identified barriers to providing medication information, family ability to provide medication information, and family suggestions to improve the medication reconciliation process.

DESIGN AND METHODS.  One hundred families with a child with a chronic condition on daily‐prescribed medication completed a 10‐question survey.

RESULTS.  Families identified not knowing, forgetting, and ability to provide information as the main reasons for not bringing medication. Half of the families that did not bring medication could not provide complete information. Families wanted to be reminded multiple times in different ways.

PRACTICE IMPLICATIONS.  Many families are unable to provide complete medication information.
The Effects of Gender on the Coping Outcomes of Young Children Following an Unanticipated Critical Care Hospitalization
Authors: Small Leigh , Mazurek Melnyk Bernadette , Sidora‐Arcoleo Kimberly
Published: March 2009

PURPOSE.  A prior evaluation of the predictors of child coping outcomes following an unanticipated critical hospitalization revealed gender differences, which were explored in this study to examine patterns of behavioral change over time.

DESIGN AND METHODS.  Data from 163 mother–child (2–7 years) dyads were extracted for this study. Measures of child coping obtained 3 and 6 months following hospitalization included the Behavioral Assessment System for Children and the Post‐Hospitalization Behavior Questionnaire.

RESULTS.  Maladaptive behaviors in girls increased throughout the 6‐month posthospitalization period. Boys demonstrated a peak and then decline of those same behaviors.

PRACTICE IMPLICATIONS.  Given this information, gender‐specific child coping information can be developed for parents, which may lead to improved child outcomes.
Hatching and earliest larval stages of the priapulid worm Priapulus caudatus
Authors: Wennberg Sofia A. , Janssen Ralf , Budd Graham E.
Published: March 2009

Abstract. Here we describe the hatching and morphology of the earliest larval stages of the priapulid worm Priapulus caudatus for the first time. The hatching larva differs considerably from previously described larvae not only in its general body shape but also in its lack of a proper lorica including the typical lorica tubuli. Furthermore, no mouth opening or pharyngeal teeth have formed as yet, and the number and arrangement of scalids differ from that of later larvae. The hatching larva molts and emerges as the first lorica larva. This larva partially resembles earlier described lorica larvae, but there are a number of important differences; the first lorica larva is smaller, and the mouth opening as well as pharyngeal teeth are still yet to form. The second lorica larva is equipped with four rings of pharyngeal teeth; it shows striking similarity to the previously described larva of P. caudatus, i.e., the larva‐type 2, only differing in the scalid pattern. We conclude that the first two larval stages of P. caudatus have not been described previously. We suggest that discrepancies between the earliest lorica larvae described here and in earlier publications might depend on sub‐speciation or ecophenotypic modification of larvae collected from different localities. Our findings highlight the importance of studying the development of non‐model organisms such as priapulids under controlled laboratory conditions.