bluuebunny/crossref_metadata_2025 huggingface dataset:
How do individuals with Williams syndrome learn a route in a real‐world environment?
Authors: Farran Emily K. , Blades Mark , Boucher Jill , Tranter Lesley J.
Published: July 2009

Individuals with Williams syndrome (WS) show a specific deficit in visuo‐spatial abilities. This finding, however, derives mainly from performance on small‐scale laboratory‐based tasks. This study investigated large‐scale route learning in individuals with WS and two matched control groups (moderate learning difficulty group [MLD], typically developing group [TD]). In a non‐labelling and a labelling (verbal information provided along the route) condition, participants were guided along one of two unfamiliar 1‐km routes with 20 junctions, and then retraced the route themselves (two trials). The WS participants performed less well than the other groups, but given verbal information and repeated experience they learnt nearly all of the turns along the route. The extent of improvement in route knowledge (correct turns) in WS was comparable to that of the control groups. Relational knowledge (correctly identifying spatial relationships between landmarks), compared with the TD group, remained poor for both the WS and the MLD group. Assessment of the relationship between performance on the large‐scale route‐learning task and that on three small‐scale tasks (maze learning, perspective taking, map use) showed no relationship for the TD controls, and only a few non‐specific associations in the MLD and WS groups.
POST‐TRIAL ACCESS TO ANTIRETROVIRALS: WHO OWES WHAT TO WHOM?
Authors: MILLUM JOSEPH
Published: July 2009

Many recent articles argue that participants who seroconvert during HIV prevention trials deserve treatment when they develop AIDS, and there is a general consensus that the participants in HIV/AIDS treatment trials should have continuing post‐trial access. As a result, the primary concern of many ethicists and activists has shifted from justifying an obligation to treat trial participants, to working out mechanisms through which treatment could be provided. In this paper I argue that this shift frequently conceals an important assumption: that if there is an obligation to supply treatment, then any party who could provide it may be prevailed upon to discharge the obligation. This assumption is false. The reasons why trial participants should get ART affect who has the duty to provide it. We should not burden governments with the obligations of sponsors, nor researchers with the obligations of the international community. And we should not deprive a group of treatment because their need is less salient than that of research participants. Insisting otherwise may lead to people being wrongfully deprived of access to antiretrovirals.
A PRECAUTIONARY PRINCIPLE FOR DUAL USE RESEARCH IN THE LIFE SCIENCES
Authors: KUHLAU FRIDA , HÖGLUND ANNA T. , EVERS KATHINKA , ERIKSSON STEFAN
Published: July 2009

Most life science research entails dual‐use complexity and may be misused for harmful purposes, e.g. biological weapons. The Precautionary Principle applies to special problems characterized by complexity in the relationship between human activities and their consequences. This article examines whether the principle, so far mainly used in environmental and public health issues, is applicable and suitable to the field of dual‐use life science research. Four central elements of the principle are examined: threat, uncertainty, prescription and action. Although charges against the principle exist – for example that it stifles scientific development, lacks practical applicability and is poorly defined and vague – the analysis concludes that a Precautionary Principle is applicable to the field. Certain factors such as credibility of the threat, availability of information, clear prescriptive demands on responsibility and directives on how to act, determine the suitability and success of a Precautionary Principle. Moreover, policy‐makers and researchers share a responsibility for providing and seeking information about potential sources of harm. A central conclusion is that the principle is meaningful and useful if applied as a context‐dependent moral principle and allowed flexibility in its practical use. The principle may then inspire awareness‐raising and the establishment of practical routines which appropriately reflect the fact that life science research may be misused for harmful purposes.
DEFENDING THE DUTY TO RESEARCH?
Authors: BRASSINGTON IAIN
Published: July 2009

In 2005, John Harris published a paper in the Journal of Medical Ethics in which he claimed that there was a duty to support scientific research. With Sarah Chan, he defended his claims against criticisms in this journal in 2008. In this paper I examine the defence, and claim that it is not powerful. Although he has established a slightly stronger position, it is not clear that the defence is sufficiently strong to show that there is a duty to support scientific research. Important questions about fairness, about rescue, and about the relationship between reasons and obligations to act can still be raised; and these questions are important enough to destabilize the defence.
The Formation of Group Affect and Team Effectiveness: The Moderating Role of Identification
Authors: Tanghe Jacqueline , Wisse Barbara , Van Der Flier Henk
Published: July 2009

In the current research we use the social identity perspective to enhance our understanding ofgroup affect(i.e. a collectively shared pattern of affective states among group members). Because higheridentification(i.e. the extent to which group members define themselves in terms of their group membership) is related to higher attentiveness to fellow group members, we expected that group identification would foster affective convergence, and that the effects of group affective tone on team effectiveness would be stronger for higher identifying groups. A survey of teams (n=71 teams) confirmed our expectations. A scenario experiment (n=121 participants) added to our findings by showing that identification does indeed lead group members to affectively converge to their fellow group members and that this affective convergence, in turn, explains subsequent team‐oriented attitudes. Our study testifies to the notion that team managers may want to take notice of and manage affect in work groups, because, especially in higher identifying teams, affect may spread among team members and influence the team's effectiveness.
Virile Turks and Maiden Ireland: Gender and National Identity in Early Modern English Travel Literature
Authors: Suranyi Anna
Published: July 2009

This article examines the role of gender in depictions of national identity in early modern English travel literature. I show that human sexual relationships were believed to be echoed in relations between territories, which were often represented as masculine or feminine. Travellers used metaphors representing marriage, seduction and rape to describe geopolitical relationships, including colonialism, tribute payments and rebellion. Representations of Ireland and the Irish, and the Ottoman Empire and the Turks are among the most revealing. I argue that such metaphors were especially favoured by travel writers because gender was believed to be inherently mutable, thus providing a variety of easily understood and mutually accepted narratives to describe international political relationships.
A Grocer's Tale: Gender, Family and Class in Early Nineteenth‐Century Manchester
Authors: Barker Hannah
Published: July 2009

This article examines the diary of George Heywood, a journeyman grocer turned small shopkeeper, who moved to Manchester from Huddersfield in 1809. Heywood's modest lifetime ambitions were to own a grocery shop and find a companionable wife. As a lower‐middle‐class man of humble means and limited ambitions, Heywood does not fit the heroic mould of those working‐class diarists and autobiographers of the nineteenth century that have more readily captured historians’ attention. Yet it is precisely this ‘ordinariness’ that makes Heywood's journal important. His smaller‐than‐life adventures are the very stuff of lower‐middle‐class life, and reveal something of a petit‐bourgeois world from which historians and social commentators have traditionally shied away. His diary allows us to glimpse one form of masculine identity that both fits with and complicates our notions of ‘bourgeois’ masculinity in this period.
Christening Masculinity? Catholic Action and Men in Interwar Belgium
Authors: Van Osselaer Tine
Published: July 2009

Masculine reactions to the ‘feminisation of Christianity’ among Protestants have been widely explored; the Catholic case is less well known. This article focuses on Catholic Action, an organisation regarded as specifically appealing to men. Through an analysis of the discourses of Catholic Action in Belgium, it examines how important masculine involvement was for Belgian Catholicism and how Catholic Action ‘christened’ masculinity. The article also analyses Catholic femininity. It examines the ways that the ideal Catholic man and woman and their corresponding gendered behaviour and role models were defined in relation to each other and the various forms that these ideals assumed.
Ceremony and Citizenship: African American Weddings, 1945–60
Authors: Dunak Karen M.
Published: July 2009

Following the Second World War, many Americans embraced the white wedding – an event marked by conspicuous consumption, gendered roles and responsibilities, and welcoming of ‘traditions’ such as formal dress, proper vows and post‐ceremony reception. For aspiring, middle‐class and elite African Americans, the wedding served a dual purpose. Through the ceremony, they demonstrated adherence to the ideals of post‐war American citizenship while preserving distinct cultural practices and values. Focusing primarily on the upwardly mobile black community of Indianapolis between 1945 and 1960, this article emphasises the wedding as a site of both personal and public significance. Adoption and enactment of the white wedding reinforced the strength of the black family and declared African Americans’ rightful belonging to the American middle‐class community.
Foreign Investment and Trade in Cuban Development: A 50‐Year Reassessment with Emphasis on the Post‐1990 Period
Authors: APONTE‐GARCÍA MARIBEL
Published: July 2009

This article provides a 50‐year reassessment of foreign investment and trade in Cuba and locates this analysis within Cuban debates on development and the economics of transition. Transformations contextualised in these debates cover three periods. The 1959–1989 period was characterised by nationalisations and expropriations, the imposition of the US trade embargo, and the trade and economic assistance agreements signed with the Soviet Union. The Special Period crisis emerged in the 1990s and Cuba had to turn to foreign investment and alternative trade options while continuing to reject the adoption of open regionalism and neoliberal policies. The 2005–2008 period was characterised by Cuba's incorporation into the Bolivarian Alternative, a new regional integration model.
Genetic diversity of endangered brown bear (Ursus arctos) populations at the crossroads of Europe, Asia and Africa
Authors: Calvignac Sébastien , Hughes Sandrine , Hänni Catherine
Published: July 2009

Aim  Middle East brown bears (Ursus arctos syriacus Hemprich and Ehrenberg, 1828) are presently on the edge of extinction. However, little is known of their genetic diversity. This study investigates that question as well as that of Middle East brown bear relationships to surrounding populations of the species.

Location  Middle East region of south‐western Asia.

Methods  We performed DNA analyses on 27 brown bear individuals. Twenty ancient bone samples (Late Pleistocene to 20th century) from natural populations and seven present‐day samples obtained from captive individuals were analysed.

Results  Phylogenetic analyses of the mitochondrial sequences obtained from seven ancient specimens identify three distinct maternal clades, all unrelated to one recently described from North Africa. Brown bears from Iran exhibit striking diversity (three individuals, three haplotypes) and form a unique clade that cannot be linked to any extant one. Individuals from Syria belong to the Holarctic clade now observed in Eastern Europe, Turkey, Japan and North America. Specimens from Lebanon surprisingly appear as tightly linked to the clade of brown bears now in Western Europe. Moreover, we show that U. a. syriacus in captivity still harbour haplotypes closely linked to those found in ancient individuals.

Main conclusion  This study brings important new information on the genetic diversity of brown bear populations at the crossroads of Europe, Asia and Africa. It reveals a high level of diversity in Middle East brown bears and extends the historical distribution of the Western European clade to the East. Our analyses also suggest the value of a specific breeding programme for captive populations.
Estimating and conserving patterns of invertebrate diversity: a test case of New Zealand land snails
Authors: Overton Jacob McC. , Barker Gary M. , Price Robbie
Published: July 2009

Aim Using New Zealand land snails as a case study, we evaluated recent spatial modelling approaches for the analysis of diversity in species‐rich invertebrate groups. Applications and prospects for improved conservation assessment were investigated.

Location New Zealand.

Methods The study used a spatially extensive and taxonomically comprehensive, plot‐based dataset on community structure in New Zealand land snails. Generalized regression analysis and spatial prediction (GRASP) was used to model and predict species richness as a function of environmental variables (including aspects of climate, soils and vegetation). Generalized dissimilarity modelling (GDM) was used to model turnover in species composition in relation to environmental and geographical distances, and to assess community similarity and the representativeness of the reserve network.

Results Observed land snail richness in 20 × 20 m plots ranged from 1 to 74 (mean 17.5). The GRASP model explained a modest 27% of the variation in richness. The GDM model explained 57% of the variation in species turnover and indicated approximately equal amounts related to environmental (Cody’s beta diversity) and geographical distance (Cody’s gamma diversity). Temperature and moisture were the most important environmental variables. Results indicate that snail distributions are not only sorted by environment but are also strongly influenced by historical effects consistent with those expected of poorly dispersing taxa that have persisted in refugia during past climatic change. The GDM model enabled spatial classifications of snail communities, highlighting diverse communities in heterogeneous regions, such as the South Island mountains, and also enabled continuous depictions of community similarity and adequacy of New Zealand’s protected natural areas network.

Main conclusions The GRASP and GDM analyses allowed us to model and depict spatial patterns of diversity in land snail communities involving 845 species, and produce community classifications and estimates of community similarity. These tools advance conservation assessment in species‐rich groups, but require further conceptual and methodological development.
Nitrite directly vasodilates hypoxic vasculature via nitric oxide‐dependent and ‐independent pathways
Authors: Pinder AG , Pittaway E , Morris K , James PE
Published: July 2009

Background and purpose: It is postulated that nitrite requires reduction to nitric oxide in order to exert its relaxant effect upon isolated hypoxic vessels. Herein, we evaluate the relative contribution of nitric oxide and characterize the downstream mechanisms of nitrite‐induced vasorelaxation.

Experimental approach: Aortic rings were treated with pharmacological agents and exposed to hypoxia (<1% O2). Following pre‐constriction, nitrite (10 µM final) was added to appropriate baths; isometric tension was recorded throughout.

Key results: Nitrite (under hypoxic conditions at physiological pH) is capable of exerting physiological effects that cannot be completely inhibited by the inhibitor of soluble guanylate cyclase (sGC), 1H [1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one or a nitric oxide scavenger (carboxy‐2‐phenyl‐4,4,5,5‐tetramethyl‐imidazoline‐1‐oxyl‐3‐oxide). Simultaneous blockade of both sGC and cyclooxygenase (COX) completely inhibited the response to nitrite. With regard to the nitric oxide‐dependent component, we confirm that aldehyde oxidase, but not xanthine oxidase or endothelial nitric oxide synthase, was important for the actions of nitrite in our model.

Conclusions and implications: Nitric oxide generated from nitrite is not exclusively responsible for the physiological actions observed in isolated hypoxic vessels. Nitrite operates via different pathways dependent on the presence or absence of endothelium to produce vasorelaxation. In intact vessels, both sGC and COX enzymes appear to be important. Irrespective of this difference in relaxation mechanism, nitrite is capable of producing the same maximum relaxation, regardless of the presence of endothelium. Having investigated possible nitrite reduction sites, we confirm that aldehyde oxidase is important for the actions of nitrite.
“Revisiting the Soviet Moment in Sub‐Saharan Africa”
Authors: Matusevich Maxim
Published: July 2009

The Soviet Union’s involvement of sub‐Saharan Africa came on the heels of African independence. During the Cold War, both the USSR and the United States engaged in an intense struggle for the “soul of Africa,” vying to win over the newly independent African nations. The Soviets offered Africans an alternative model of socio‐economic development and hoped that its implementation would result in a closer geoplitical alliance and Africa’s inevitable march toward socialism. However, these early euphoric expectations were dashed when it became clear that African nations were often pursuing their own pragmatic objectives. Even those regimes who formally committed to socialism were, in fact, using ideology and exploiting the cold war rivalries and superpower sensibilities for their own political expediency. In Angola, in Somalia, in Ethiopia, and in Southern Africa, the Soviets were left to contend with regimes and political movements that often defied their expectations. Soviet involvement in sub‐Saharan Africa diminished greatly in the wake of Mikhail Gorbachev’s reforms in the Soviet Union. With the Cold War waning and the Soviet economy in shambles, the USSR had little incentive to continue its presence in Africa. By the time of Soviet collapse in 1991, the country had lost much of its earlier clout and prominence in Africa, south of the Sahara.
Space, Place and Identities
Authors: Rohkrämer Thomas , Schulz Felix Robin
Published: July 2009

Over the last decades, many social scientists have diagnosed a ‘disappearance of space’ (Paul Virilio). Others, however, have presented persuasive arguments for a ‘spatial turn’ (Edward W. Soja) that is the demand to recognise space as a key factor for the social sciences and humanities. Following the latter argument, the article shows the importance of space which is not just a neutral box in which history takes its course. On the contrary, humans are always thrown into a historically specific world and thus linked with their environment. They are both being influenced by the world around them and constructing a social understanding of their surroundings, and it is thus the challenge for studies of space and place to situate themselves between the two reductionist positions of spatial voluntarism and spatial determinism. The survey of more theoretical and empirical studies also shows the key importance of human attachment to ‘their place’ in identity formation, on a local, regional, national and transnational level as well as through qualitative features of landscape such as mountains or plains, rich or sparse vegetation, or the question of access to rivers, lakes and the sea. Such senses of belonging orHeimatare a key aspect of human existence and political action ranging from providing an important sense of community to a dangerous exclusion of alleged ‘others’.
Evaluating the risk of hepatitis B reactivation in patients with haematological malignancies: is the serum hepatitis B virus profile reliable?
Authors: Ferraro Donatella , Pizzillo Paola , Di Marco Vito , Vultaggio Anna , Iannitto Emilio , Venezia Giovanna , Craxì Antonio , Di Stefano Rosa
Published: July 2009

Background/Aim: Patients with an occult hepatitis B virus (HBV) infection undergoing deep immunosuppression are potentially at risk of HBV reactivation. In order to assess whether a polymerase chain reaction (PCR) assay for HBV DNA in serum could be used to predict the reactivation of an occult HBV infection, we performed a retrospective study in a cohort of Sicilian patients with oncohaematological diseases.

Methods: We studied by a highly sensitive ad hoc nested PCR for serum HBV DNA 75 HBsAg‐negative oncohaematological patients requiring chemotherapy.

Results: Thirty‐three patients (44%) were HBV seronegative (anti‐HBc and anti‐HBs negative) and 42 patients (56%) were HBV seropositive (anti‐HBc and/or anti‐HBs positive). Baseline serum HBV DNA was positive in nine out of 33 HBV‐seronegative patients and in nine out of 42 HBV‐seropositive patients (27.3 vs. 21.4%; P=NS). HBsAg seroconversion was observed in five out of 33 seronegative vs. six out of 42 seropositive patients (15 vs. 14%, P=0.9), and in five out of 18 HBV DNA‐positive vs. six out of 57 HBV DNA‐negative patients (27.7 vs. 10.6%P=0.11). Hepatitis C virus infection was found in 18 patients (24.3%), although with no correlation to HBV serological status, presence of serum HBV DNA or frequency of HBsAg seroconversion.

Conclusions: In oncohaematological patients undergoing chemotherapy, highly sensitive serum HBV DNA testing at baseline has a 28% predictive ability to forecast HBsAg seroconversion in HBV DNA‐positive patients, and a 90% ability to forecast persistent HBsAg negativity in HBV DNA‐negative patients, a better performance than serological tests.
Chronic hepatitis C virus infection associated with autonomic dysfunction
Authors: Osztovits János , Horváth Tamás , Abonyi Margit , Tóth Tamás , Visnyei Zsolt , Bekö Gabriella , Csák Tímea , Lakatos Péter László , Littvay Levente , Fehér János , Kempler Péter , Kollai Márk , Szalay Ferenc
Published: July 2009

Background: Impaired autonomic function has been described in patients with chronic liver diseases from different aetiologies, and has proven to be a poor prognostic indicator. To date, it is not known how chronic hepatitis C virus (HCV) infection affects the autonomic nervous system.

Aims: In the present study, we compared cardiovagal autonomic function in patients with chronic HCV infection and healthy controls and examined the relation between autonomic function and serum levels of aminotransferases, HCV RNA, cryoglobulins, albumin and glucose.

Methods: Autonomic function was assessed in 45 treatment‐naïve patients with chronic HCV infection and in 40 healthy controls by determining spontaneous baroreflex sensitivity (BRS) and heart rate variability (HRV) indices. The R–R interval was determined by electrocardiogram recording; continuous radial artery pressure was monitored simultaneously by applanation tonometry. Laboratory analyses and quantitative polymerase chain reaction for serum HCV RNA level were performed by standard procedures.

Results: BRS and HRV time and frequency domain indices were lower in patients with HCV infection compared with healthy controls [7.1±3.4 vs. 11.5±6.5 ms/mmHg for BRS, 168.5±160.9 vs. 370.7±349.4 ms2 for low‐frequency HRV (mean±SD); P<0.01]. Multivariate analysis showed that autonomic dysfunction in HCV‐infected patients correlated with elevated alanine aminotransferase levels, but was not associated with serum HCV RNA levels and cryoglobulins.

Conclusion: Our results suggest that impaired autonomic function is caused by chronic HCV infection. Further studies are needed, however, to identify the underlying mechanisms.
Liver fat and lipid oxidation in humans
Authors: Kotronen Anna , Seppälä‐Lindroos Anneli , Vehkavaara Satu , Bergholm Robert , Frayn Keith N. , Fielding Barbara A. , Yki‐Järvinen Hannele
Published: July 2009

Background: Studies in animals show that changes in hepatic fatty acid oxidation alter liver fat content. Human data regarding whole‐body and hepatic lipid oxidation are controversial and based on studies of only a few subjects.

Aims: We examined whether whole‐body and hepatic lipid oxidation are altered in subjects with non‐alcoholic fatty liver disease (NAFLD) compared with controls.

Methods: In vivo measurements of rates of substrate oxidation and insulin sensitivity (using the euglycaemic hyperinsulinaemic clamp technique in combination with indirect calorimetry and infusion of [3‐3H]glucose) were performed in subjects with NAFLD [mean liver fat 14.0% (interquartile range 7.5–20.5%), n=29] and in control subjects [1.6% (1.0–3.0%), n=29]. Liver fat was measured using proton magnetic resonance spectroscopy. Plasma concentrations of 3‐hydroxybutyrate (3‐OHB) were measured as markers of hepatic lipid oxidation.

Results: In the basal state, substrate oxidation rates and serum 3‐OHB concentrations were comparable in subjects with and without NAFLD. Plasma 3‐OHB concentrations were similarly suppressed by insulin in both the groups. During the insulin infusion, whole‐body lipid oxidation was inversely correlated with insulin‐stimulated glucose disposal (r=−0.48, P<0.0001), which was lower in subjects with NAFLD [3.7±0.2 mg/(kg fat‐free mass min)] than in the control subjects [5.0±0.3 mg/(kg fat‐free mass min), P=0.0008].

Conclusions: Hepatic lipid oxidation is unchanged in NAFLD. Whole‐body lipid oxidation is increased because of peripheral insulin resistance. These data imply that alterations in hepatic fatty acid oxidation do not contribute to liver fat content in humans.
Protein–calorie malnutrition as a prognostic indicator of mortality among patients hospitalized with cirrhosis and portal hypertension
Authors: Sam Justina , Nguyen Geoffrey C.
Published: July 2009

Background: We conducted a nationwide analysis of the prevalence of protein–calorie malnutrition (PCM) in patients with cirrhosis and portal hypertension (PHTN) and to determine its mortality and economic impact.

Methods: We used the Nationwide Inpatient Sample (NIS) to identify admissions throughout the US with cirrhosis and PHTN between 1998 and 2005 using the International Classification of Diseases, 9th Revision diagnostic codes. Prevalence of PCM in this group of patients with cirrhosis was compared with that of general medical inpatients. The impact of PCM on in‐hospital mortality was quantified using multiple logistic regression analysis.

Results: There were 114 703 admissions with cirrhosis and PHTN in the NIS between 1998 and 2005. The prevalence of PCM was substantially higher among patients with cirrhosis and PHTN compared with general medical inpatients (6.1 vs. 1.9%, P<0.0001), with an adjusted odds ratio of 1.55 (95% CI: 1.4–1.7). There was greater prevalence of ascites (64.6 vs. 47.8%, P<0.0001) and hepatorenal syndrome (5.1 vs. 2.8%, P<0.0001) among those with PCM and cirrhosis. In‐hospital mortality was two‐fold higher among patients with cirrhosis and PCM (14.1 vs. 7.5%, P<0.0001), with an adjusted mortality of 1.76 (95% CI: 1.59–1.94). PCM was associated with greater length of stay (8.7 vs. 5.7 days, P<0.0001) and hospital charges (US$36 818 vs. US$22 673; P<0.0001) among patients with cirrhosis.

Conclusions: PCM is more common among patients with cirrhosis and PHTN than the general medical population, and is associated with higher in‐hospital mortality and resource utilization. PCM may be an indicator of greater disease severity and should be routinely assessed on admission.
Analysis of the efficacy of treatment with peginterferon α‐2a and ribavirin in patients coinfected with hepatitis B virus and hepatitis C virus
Authors: Yu Jian‐Wu , Sun Li‐Jie , Zhao Yong‐Hua , Kang Peng , Gao Jie , Li Shu‐Chen
Published: July 2009

Objective: To study the virological features of patients coinfected with hepatitis B virus (HBV) and hepatitis C virus (HCV) and the efficacy of combination therapy with peginterferon α‐2a and ribavirin in these patients.

Methods: The epidemiological and virological data of 50 patients coinfected with HBV and HCV were analysed. The virological response rates of patients treated with peginterferon α‐2a and ribavirin between the HBV and HCV coinfection group and the HCV monoinfection group were compared.

Results: HCV‐dominant virus strains accounted for 92.0% of the 50 coinfected individuals, and HCV‐ and HBV‐dominant virus strains accounted for the remaining 8.0%. The HBV DNA level of the patients coinfected with HBV and HCV was 4.6±0.9 log10 copies/ml, which was significantly lower than that in the HBV monoinfection group (5.9±1.2 log10 copies/ml) (t=5.964, P<0.01). The HBeAg‐positive rate (12.0%, 6/50) of the coinfection group was significantly lower than (45.3%, 19/42) that of the HBV monoinfection group (χ2=12.743, P<0.01). The partial early virological response (pEVR) rate and the end‐of‐treatment virological response (ETVR) rate (50.0%, 15/30; 90.0%, 27/30) of patients with genotype 1 in the coinfection group were significantly higher than those (16.0%, 4/25; 56.0%, 14/25) in the HCV monoinfection group (χ2=6.971, P=0.008; χ2=8.307, P=0.004). The relapse rate (55.6%, 15/27) of patients with genotype 1 in the coinfection group was significantly higher than that (21.4%, 3/14) in the HCV monoinfection group (χ2=4.360, P=0.037). The sustained virological response (SVR) rate (40.0%, 12/30) of patients with genotype 1 in the coinfection group was compared with that of the HCV monoinfection group (44.0%, 11/25) (χ2=0.090, P=0.765). There was no significant difference in the on‐treatment virological response, ETVR, SVR and relapse rates between two groups for patients with genotype 2. The incidence of side effects (30%, 15/50) of patients in the coinfection group was significantly higher than that (13%, 6/46) in the HCV monoinfection group (χ2=4.031, P=0.045). The reactivation rate of HBV DNA (33.3%, 9/27) with HCV SVR was significantly higher than that of patients without SVR (8.7%, 2/23) (χ2=4.393, P=0.036).

Conclusions: The replication of HBV was suppressed, and HCV was the dominant virus strain. Compared with HCV‐monoinfected patients, pEVR, ETVR and relapse rates of patients with genotype 1 in the coinfection group were high, while they shared similar SVR rates. HBV and HCV coinfection had no impact on the rate of virological response for genotype 2.
Transtactin: a universal transmembrane delivery system forStrep‐tag II‐fused cargos
Authors: Moosmeier Markus A. , Bulkescher Julia , Reed Jennifer , Schnölzer Martina , Heid Hans , Hoppe‐Seyler Karin , Hoppe‐Seyler Felix
Published: July 2009

The delivery of molecules into cells poses a critical problem that has to be solved for the development of diagnostic tools and therapeutic agents acting on intracellular targets. Cargos which by themselves cannot penetrate cellular membranes due to their biophysical properties can achieve cell membrane permeability by fusion to protein transduction domains (PTDs). Here, we engineered a universal delivery system based on PTD‐fusedStrep‐Tactin, which we named Transtactin. Biochemical characterization of Transtactin variants bearing different PTDs indicated high thermal stabilities and robust secondary structures. Internalization studies demonstrated that Transtactins facilitated simple and safe transport ofStrep‐tag II‐linked small molecules, peptides and multicomponent complexes, or biotinylated proteins into cultured human cells. Transtactin‐introduced cargos were functionally active, as shown for horseradish peroxidase serving as a model protein. Our results demonstrate that Transtactin provides a universal and efficient delivery system forStrep‐tag II‐fused cargos.
Quantitative proteomic analysis of the cerebrospinal fluid of patients with multiple sclerosis
Authors: Liu Shilian , Bai Shumei , Qin Zhaoyu , Yang Yinrong , Cui Yazhou , Qin Yanjiang
Published: July 2009

The diagnosis of multiple sclerosis (MS) is challenging for the lack of a specific diagnostic test. Recent researches in quantitative proteomics, however, offer new opportunities for biomarker discovery and the study of disease pathogenesis. To find more potential protein biomarkers, we used two technologies, 2‐dimensional fluorescence difference in‐gel electrophoresis (2D‐DIGE), followed by matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) and ultra‐performance liquid chromato‐graph coupled with quadrupole time‐of‐flight mass spectrometry (UPLC/Q‐TOF MS), to quantitatively analyse differential proteomic expression in the cerebrospinal fluid (CSF) between patients with MS (the experiment group) and patients with other neurological diseases (ONDs; the control group). Analysis by the former technology identified more than 43 different protein spots (39 proteins), of which 17 spots (13 proteins) showed more than 1.5‐fold difference in abundance as analysed by DeCyder software (GE Healthcare, Piscataway. NJ, USA) between the MS and the ONDs groups. The expression of five protein spots was elevated and the expression of 12 protein spots was decreased in the MS group. Meanwhile, the latter method, UPLC/Q‐TOF MS showed 68 different proteins. There were 45 proteins with a difference of more than 1.5 folds between the two groups, in which the expression of 20 proteins was elevated and the expression of 25 proteins was decreased in the MS group. Data provided by the two methods indicated that the proteins overlapped ratio was 27% in the 26 significant proteins that had the same regulation tendency. The differential CSF proteins were analysed further by biological network and it revealed interaction of them. The subsequent ELISA measuring the concentration of cystatin C (P < 0.01), which was one of the proteins discovered simultaneously with the two technologies, confirmed the results of the two quantitative proteomic analysis. The combination of the two quantitative proteomic technologies was helpful in discovering differentially expressed proteins that may have a connection with MS disease physiology and serve as useful biomarkers for diagnosis and treatment of MS diseases.
A finding of granuloma faciale associated with basal cell carcinoma
Authors: Kamalpour Loebat , Gammon Bryan , Larsen Fiona , Cashman Robert , Cockerell Clay
Published: July 2009

The clinical differential diagnosis of violaceous plaques on the face is broad and includes both neoplasms and inflammatory dermatoses. We report the first case of a basal cell carcinoma (BCC) superficial to an underlying granuloma faciale (GF). This is a single case report with clinicopathological correlation. Histological examination of a skin biopsy from the cheek revealed superficial BCC and GF. This case constitutes the first reported finding of coincident GF and BCC.
Acantholytic tumor of the nail: acantholytic dyskeratotic acanthoma
Authors: Sass Ursula , Kolivras Athanassios , Richert Bertrand , Moulonguet Isabelle , Goettmann‐Bonvallot Sophie , Anseeuw Marleen , Theunis Anne , André Josette
Published: July 2009

Acantholytic dyskeratotic acanthomas of the skin have been recently described in several publications. They differ from acantholytic acanthomas by the presence of dyskeratosis. However these tumors have never been described in nails. We report three cases localized on the thumb nail.
Indolent CD8+ lymphoid proliferation of the ear: A phenotypic variant of the small‐medium pleomorphic cutaneous T‐cell lymphoma?
Authors: Beltraminelli Helmut , Müllegger Robert , Cerroni Lorenzo
Published: July 2009

Background: Recently, Petrella et al. described four patients with an unusual CD8+ lymphoid proliferation arising on the ear. These cases do not correspond clearly to any recognized category of cutaneous T‐cell lymphoma (CTCL) described in the World Health Organization (WHO)/European Organization for Research and Treatment of Cancer (EORTC) 2005 classification.

Methods and Results: Three patients (all men; median age 64; range: 61‐69) presented with plaques or small tumors localized on the ears. All lesions showed histopathologically a dense, diffuse infiltration of lymphocytes within the entire dermis without epidermotropism. Cytomorphology revealed predominance of medium‐sized pleomorphic lymphocytes. Immunohistochemistry showed a cytotoxic phenotype (CD3 + /CD4 −/CD8 +). Polymerase chain reaction (PCR) analysis of the T‐cell receptor (TCR)‐gamma gene revealed a monoclonal rearrangement in two of three patients. Follow‐up data of two patients were available; one is alive without skin or systemic manifestations of the disease after 28 months, whereas the other is alive with persistent skin disease after 7 months.

Conclusions: Our observation confirms that some patients present with a peculiar lymphoid proliferation of small‐medium pleomorphic cytotoxic lymphocytes located on the ear, probably representing a phenotypic variant of the cutaneous small/medium pleomorphic T‐cell lymphoma (CSMPTCL). These cases should not be misinterpreted as a high‐grade cytotoxic lymphoma.
PRP with subcorneal acantholysis: case report and review
Authors: Sebastian Anita , Koff Amy Beth , Goldberg Lynne J.
Published: July 2009

Although the clinical findings of pityriasis rubra pilaris (PRP) are striking, the microscopic diagnosis can be difficult because changes can be subtle and can overlap with other skin diseases. Suprabasal acantholysis can be seen in PRP, mimicking pemphigus vulgaris. We report a patient with PRP whose initial biopsies demonstrated subcorneal acantholysis mimicking pemiphigus foliaceus.
The Histopathological characteristics of livedo reticularis
Authors: In Sung Il , Han Jae Ho , Kang Hee Young , Lee Eun‐So , Kim You Chan
Published: July 2009

Background: Livedo reticularis (LR) is a skin disorder characterized by a reddish‐blue mottling of the skin in a “fishnet” reticular pattern. The aim of this study was to investigate the major histopathological characteristics of LR and determine whether the histopathology of LR is more common in whitish areas or in the erythematous areas.

Methods: A clinical survey was carried out that included 16 patients with LR. The histopathological features were investigated with immunostains for factor VIII‐related antigen, as well as routine hematoxylin‐eosin.

Results: There were no significant differences in thrombi, arterial obliteration, or RBC aggregates between the central blanched area and the peripheral erythematous areas. The computer‐assisted image analyses of factor VIII‐related antigen‐stained sections revealed no significant difference in the number of dermal blood vessels and telangiectasia between the areas studied. There were nine cases that showed one or more of the histopathological features of LR in either the central blanched areas or the peripheral erythematous areas.

Conclusion: Our findings suggest that multiple punch biopsies should be performed in patients suspected of LR including both the peripheral erythematous and central whitish areas to increase the diagnostic yield.
Effectiveness of imiquimod limited to dermal melanoma metastases, with simultaneous resistance of subcutaneous metastasis
Authors: Turza Kristin , Dengel Lynn T. , Harris Rebecca C. , Patterson James W. , White Kevin , Grosh William W. , Slingluff Craig L.
Published: July 2009

Successful management of epithelial skin cancers with imiquimod 5% cream (Aldara®), an immunomodulatory agent, led to speculation that it may promote an immune response against melanoma. Studies, mostly case reports, have assessed the value of imiquimod as a topical treatment for dermal melanoma metastases that prove difficult to manage surgically. The precise value of imiquimod, however, in treatment of dermal and subcutaneous metastases remains unclear. A case at our institution elucidates histopathologically that subcutaneous metastases may progress despite excellent treatment of superficial dermis in the same location. In preparation for a clinical trial using imiquimod to treat patients with dermal melanoma metastases, we have treated several patients off protocol. We present a case report in which the observed changes are documented photographically and histologically. The patient experienced dramatic improvement in the locally treated dermis with concurrent regional treatment failure in the subcutaneous space. Our experience supports growing evidence that imiquimod for some provides an effective option for dermal disease. The unique histological documentation we provide regarding the differential effectiveness of imiquimod in treating various tissue components may help guide future investigations regarding optimal clinical application of imiquimod therapy for melanoma metastases.
White sponge nevus presenting as genital lesions in a 28‐year‐old female
Authors: Cutlan J.E. , Saunders N. , Olsen S.H. , Fullen D.R.
Published: July 2009

A case is presented of white plaques occurring predominantly on the vulvar mucosa of a 28‐year‐old female diagnosed as white sponge nevus (WSN). WSN is a rare, autosomal dominant disorder involving mucous membranes. It predominantly affects the oral mucosa; however, it has been reported to rarely involve extraoral mucosal sites. In this case, histology and family history were key features leading to the correct diagnosis. WSN is an extremely rare cause of vulvar leukoplakia, yet it is important to recognize to allow for appropriate genetic counseling of this autosomal dominant disorder and to avoid misdiagnosis and the potential for subsequent exposure to ineffective treatment modalities.

Cutlan JE, Saunders N, Olsen SH and Fullen DR. White sponge nevus presenting as genital lesions in a 28‐year‐old female.
Molluscum contagiosum involving an epidermoid cyst with xanthogranuloma‐like reaction in an HIV‐infected patient
Authors: Aldabagh Bishr , Ly Micki N , Hessel Adam B , Usmani Arif S.
Published: July 2009

Background: Molluscum contagiosum (MC) causes characteristic cutaneous lesions that occur mainly in children, sexually active adults, and immunocompromised individuals, especially those with human immunodeficiency virus (HIV) infection. Patients infected with HIV, particularly those with advanced disease, have an increased incidence, up to 33.3%, of MC in non‐anogenital areas. MC has been rarely found to be associated with epidermoid cysts.

Case report: A 44‐year‐old male with HIV infection presented with the complaint of a‐3‐month history of a tender nodule on the left neck. H&E stained sections showed a ruptured cyst, lined with squamous epithelium showing cytopathic changes of MC, and a xanthogranuloma‐like inflammatory reaction with characteristic Touton‐type giant cells.

Conclusion: MC infections are common, however MC associated with epidermoid cysts is infrequent. A few cases of MC occurring in epidermoid cysts have previously been reported. We are presenting a case of MC involving an epidermoid cyst in an AIDS patient, with a unique xanthogranuloma‐like reaction. Xanthogranulomatous (XG) reactions have been infrequently reported in association with other viral infections, however, poxvirus‐associated XG reaction has only been observed in animals. This is the first reported case of MC‐associated XG reaction in humans.

Aldabagh B, Ly MN, Hessel AB, Usmani AS. Molluscum contagiosum involving an epidermoid cyst with xanthogranuloma‐like reaction in an HIV‐infected patient.
Age‐related improvement in reproductive performance in a long‐lived raptor: a cross‐sectional and longitudinal study
Authors: Blas Julio , Sergio Fabrizio , Hiraldo Fernando
Published: July 2009

In numerous iteroparous species, mean fecundity increases with age. Such improvement has been explained by: a) progressive removal of inferior breeders from the breeding population (selection‐hypothesis); b) delayed breeding of higher‐quality phenotypes (delayed‐breeder‐hypothesis); c) longitudinal enhancement of skills associated with age per se (age‐hypothesis); d) progressive improvement in the capability to conduct specific tasks facilitated by accumulated experience (breeding‐experience‐hypothesis); and e) increasing parental investment promoted by declining residual reproductive values (restraint‐hypothesis). To date, there have been few comprehensive tests of these hypotheses. Here, we provide such a study using a long‐term dataset on a long‐lived raptor, the black kite Milvus migrans (maximum lifespan 23 yr). Kites delayed breeding for 1–7 yr and all measures of breeding performance increased linearly or quadratically up to 11 yr of age. There was no support for the delayed‐breeder‐hypothesis: superior phenotypes did not delay breeding longer. Superior breeders were retained longer in the breeding population, consistent with the selection‐hypothesis. All measures of breeding performance increased longitudinally within individuals, supporting the age‐hypothesis, while some of them increased with accumulated previous experience, supporting the breeding‐experience‐hypothesis. Some analyses suggested the existence of trade‐offs between reproduction in the early years of life and subsequent survival, partially supporting the restraint‐hypothesis. The pattern of age‐related improvements in breeding rates observed at the population‐level could be ascribed to the combined effect of the progressive removal of inferior phenotypes from the breeding population and the individual‐level lack of specific skills which are progressively acquired with time and experience. It was also compatible with a longitudinal increase in reproductive investment. Results from previous studies suggest that different mechanisms may operate in different species and that age‐related improvements in reproduction may be frequently promoted by the complex interplay between longitudinal improvements and changes in the relative frequency of productive phenotypes in the breeding population.
Classification, incidence and survival analyses of children with CNS tumours diagnosed in Sweden 1984–2005
Authors: Lannering Birgitta , Sandström Per‐Erik , Holm Stefan , Lundgren Johan , Pfeifer Susan , Samuelsson Ulf , Strömberg Bo , Gustafsson Göran ,   for the Swedish Childhood CNS Tumor Working Group (VCTB)
Published: July 2009

Aim:  Primary tumours in the central nervous system (CNS) are the second most common malignancy in childhood after leukaemia. Sweden has a high incidence and a high‐survival rate in international comparative studies. This has raised the question about the type of tumours included in the Swedish Cancer registry. We therefore compared international data to the Swedish Childhood Cancer registry.

Methods:  Central nervous system tumours registered in the Swedish Childhood Cancer Registry were reclassified according to ICCC‐3. Incidence and survival analyses were performed in the study population.

Results:  There were 1479 children (<15 years) in Sweden diagnosed with CNS tumours 1984–2005. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 4.2/100 000 children. The survival rates have not improved significantly between the two time periods before/after 1995 (70% vs. 74%; p = 0.10).

Conclusions:  The mean annual incidence of children with CNS tumours was 4.2/100 000 and has not increased during the study period. Survival rate for brain tumours at 10 years follow‐up was 72%.