bluuebunny/crossref_metadata_2025 huggingface dataset:
How fire and climate shaped grass-dominated vegetation and forest mosaics in northern South Africa during past millennia
Authors: Breman Elinor , Gillson Lindsey , Willis Kathy
Published: April 2011

Grassland and savanna are globally important ecosystems, both ecologically and economically. These grass-dominated systems are at risk from current and future climate change and increasing anthropogenic impact. Key questions for understanding the resilience and variability of grass-dominated ecosystems under current and future environmental conditions include: How have these systems responded to climate change and disturbance in the past? What are the principal driving agents responsible for their present-day composition and distribution? Do the palaeoecological data provide evidence for feedbacks between climate, fire and anthropogenic activities? In this study, the temporal dynamics of grassland, savanna and forest in the summer rainfall region of northern South Africa were reconstructed for the last ~6500 years. Palaeoecological techniques used include analyses of fossil pollen, charcoal and stable isotopes. Data from two sites located at the present-day grassland-savanna ecotone in Mpumalanga province of South Africa are reported. Results indicate that a mosaic of grassland, savanna and Podocarpus forest occupied the landscape throughout the late Holocene, with grassland and forest dominating higher altitudes, and savanna and forest lower altitudes. Podocarpus forest retreated and grass-dominated vegetation expanded its range around 1800 cal. yr BP at the lower altitude site (Lowveld) and 600 cal. yr BP at the higher altitude site (Highveld), representing a change from a stable state forest savanna/grassland mosaic to an increasingly grass-dominated system. Climatic stress, changes in fire regime and anthropogenic impact led to the vegetation transitions recorded, and resulted in changes in water and nutrient cycles. In an increasingly warm world, with fluctuating water availability and heightened anthropogenic use of natural resources, the future of grass-dominated ecosystems appears far from stable.
‘It’s like taking poison to kill poison but I have to get better’: A qualitative study of beliefs about medicines in Rheumatoid arthritis and Systemic lupus erythematosus patients of South Asian origin
Authors: Kumar K , Gordon C , Barry R , Shaw K , Horne R , Raza K
Published: April 2011

Objective: To investigate factors that influence beliefs about medicines in patients of South Asian origin with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods: Qualitative methodology was used to explore the health beliefs of South Asian patients and in particular the factors that influenced their beliefs about medicines and disease modifying anti-rheumatic drugs (DMARDs). Thirty two patients with RA and SLE took part in focus group discussions. Patients who chose to participate in focus groups conducted in English were compared with those who chose to participate groups conducted in Punjabi or Urdu. Results: Three main themes emerged to explain patients beliefs about medicines: (1) Beliefs about the necessity of DMARDs; (2) Concerns about DMARDs and other prescribed medicines including: (a) long-term side-effects; (b) the apparent lack of efficacy of some therapies; (c) concerns about changing from one drug to another and the large numbers of different medicines being taken; (3) Contextual factors which informed the patient’s view on the necessity for particular medicines and concerns about them including: (a) beliefs about the causes of disease and the influence of religious beliefs on this; (b) barriers to communication with health care professionals about the medications being prescribed in clinic. In addition, our data revealed that these beliefs about DMARDs had important consequences for patient behaviour, including the use of traditional dietary and other non-pharmacological approaches. There were differences in views expressed between those who chose to speak in English and those who did not. Conclusion: This study has identified themes that explain previous findings of negative beliefs about medicines in patients of South Asian origin. Beliefs about the causes of disease had an important impact on the way some patients viewed medicines for RA and SLE. This will have implications for educational programmes designed to promote patient involvement in disease management.
Benefit sharing and biobanking in Australia
Authors: Nicol Dianne , Critchley Christine
Published: April 2011

Biobanks are essential tools for facilitating biomedical research, because they provide collections of human tissue linked with personal information. There is still little understanding of the underlying reasons why people participate in biobanking in the increasingly commercialised and internationalised biomedical research environment. This paper reports the results of an Australia-wide telephone survey. The paper analyses the types of obligations that members of the public may wish to see incorporated in biobank benefit sharing arrangements and the extent to which their views might be influenced by underlying norms of sharing behaviour. Latent class analysis of the dataset reveals three distinct classes of respondents. We link one of these with the norm of reciprocity, one with the norm of social responsibility. The third is not clearly linked with any one norm of sharing behaviour. The implications of these findings on biobank benefit sharing arrangements are discussed.
The Impact of Stock Index Futures on the Turkish Spot Market
Authors: Çağlayan Ebru
Published: April 2011

The aim of this work is to investigate the impact of the introduction of index futures on the volatility of the underlying Turkish spot market. For this purpose, symmetric and asymmetric conditional-volatility models have been employed by using the Istanbul Stock Exchange 30 Index (ISE30) daily returns. The evidences indicate that there have been significant changes in the structure of volatility in the ISE30 spot market, following the onset of futures trading. It has also been found that the asymmetric effect is relevant in the post-futures period.
Negotiating Transnational Identities on Indo-Myanmar Border
Authors: Sharma Sukanya
Published: April 2011

The identity of the people in the Indo-Myanmar border in Northeast India is that they belong to the Indo-Mongoloid racial stock and speak languages belonging to the Tibeto-Burman group. Most of these groups trace their origin to some part of Southeast Asia. The historical routes both constrain and empower movements across borders and cultures. But traffic across borders has been controlled by the articulation of homelands or safe spaces assigned to a group of a particular identity. Inspite of political division, the ethnically and culturally similar people inhabiting both sides of the international border have maintained constant cross-border movements. It is a shared landscape divided politically. This people with lives on both sides of the international border often find themselves victimised for crimes against the state. For this people besides the territorial road, there is also an extraterritorial road to the other side of the political border. This is a reality which is the basis of their identity. This article proposes a framework for international trade between ‘local border points’ in the Indo-Myanmar border, where only the residents in immediately neighbouring provinces/states can cross borders and trade freely. It is a hope that this will negotiate the conversion of a common shared space to a transnational space in this globalised world.
The Emotional Journey of Women Experiencing a Breast Abnormality
Authors: Blow Adrian J. , Swiecicki Paul , Haan Pam , Osuch Janet R. , Symonds Laura L. , Smith Stephanie S. , Walsh Kyle , Boivin Michael J.
Published: April 2011

Using grounded theory, a multidisciplinary study team compared the narratives of 30 women who had recently experienced a breast cancer scare. Even though 10 women received a benign diagnosis, all women reported a difficult time prediagnosis, characterized by an array of emotions and contemplation of the meaning of life. Diagnosis separated the two groups with emotional relief dominant for the benign group and intensification of emotions for the cancer group. For those diagnosed with cancer, three factors contributed to arriving at a point of acceptance about the diagnosis and treatment: (a) sustained coping mechanisms; (b) a belief system that shifted the meaning of the cancer experience; and (c) the ability to manage non-cancer-related stressful events. Implications include the need for tailored biopsychosocial treatments that focus on reducing stress, enhancing support systems, reframing beliefs about the illness, and providing the opportunity for the women to talk about their experiences.
Power, Pain, and the Interspecies Politics of Foie Gras
Authors: Youatt Rafi
Published: April 2011

This article examines the practices, logics, and politics of foie gras production and consumption. It argues that scholars need to rethink both pain and sentience to account for the fact that ducks are responsive, and not just reactive. Rather than using the capacities of animals to judge when power relations between species are acceptable, it suggests that scholars should start with the power relations themselves to account for how animal and human experiences are made.
Repeated Doses of Oral and Subcutaneous Heparins Have Similar Antithrombotic Effects in a Rat Carotid Arterial Model of Thrombosis
Authors: Hiebert Linda M. , Ping Tilly , Wice Sandra M.
Published: April 2011

Although heparins are usually injected intravenously or subcutaneously, antithrombotic activity is observed in rat models following single oral heparin doses. Since repetitive dosing is usually needed for thromboprophylaxis, study objectives were to determine whether repetitive oral heparin prevented arterial thrombosis and to compare effectiveness to subcutaneous administration. Wistar rats were given subcutaneous or oral unfractionated heparin ([UFH] 1 mg/kg per 48 h), low-molecular-weight heparin ([LMWH] tinzaparin, 0.1 mg/kg per 12 h), or saline for 30 days. On the last day, thrombosis was initiated by placing 30% FeCl3-soaked filter paper on the distal carotid. Subsequent flow measurements, for a 60-minute period, included recorded time of initial thrombus formation (time till thrombus begins [TTB]), and time until carotid occlusion (time till occlusion [TTO]). The formed thrombus was dried and weighed. The activated partial thromboplastin time (aPTT), anti-factor Xa, and antithrombin activity were determined from the plasma. Both oral and subcutaneous heparins significantly increased TTB and TTO. Time of initial thrombus formations were 12.6 ± 1.1, 21.2 ± 2.2, 25.3 ± 3.9, 21.7 ± 3.1, and 21.3 ± 1.7 minutes and TTOs were 29.3 ± 3.6, 54.8 ± 4.0, 60.0 ± 0.3, 56.7 ± 3.3, and 58.3 ± 1.7 minutes (mean ± SEM) for control, subcutaneous UFH, oral UFH, subcutaneous LMWH, and oral LMWH, respectively. Thrombus weight was 2.52 ± 0.29 g in control and was reduced to 43%, 23%, 33%, and 28% of control weight for subcutaneous UFH, oral UFH, subcutaneous LMWH, and oral LMWH, respectively. Thrombus weight was significantly less for oral compared to subcutaneous UFH. The aPTT for oral UFH, and anti-factor Xa activity in the LMWH-treated groups were significantly greater than control (two-tailed t tests). These findings confirm that orally administered heparins are absorbed. Repeated treatment with oral heparin showed similar antithrombotic activity compared to subcutaneous heparin. Oral heparin use for arterial thromboprophylaxis should be further investigated.
A Global Perspective on Child Sexual Abuse: Meta-Analysis of Prevalence Around the World
Authors: Stoltenborgh Marije , van IJzendoorn Marinus H. , Euser Eveline M. , Bakermans-Kranenburg Marian J.
Published: April 2011

Our comprehensive meta-analysis combined prevalence figures of childhood sexual abuse (CSA) reported in 217 publications published between 1980 and 2008, including 331 independent samples with a total of 9,911,748 participants. The overall estimated CSA prevalence was 127/1000 in self-report studies and 4/1000 in informant studies. Self-reported CSA was more common among female (180/1000) than among male participants (76/1000). Lowest rates for both girls (113/1000) and boys (41/1000) were found in Asia, and highest rates were found for girls in Australia (215/1000) and for boys in Africa (193/1000). The results of our meta-analysis confirm that CSA is a global problem of considerable extent, but also show that methodological issues drastically influence the self-reported prevalence of CSA.
A Systematic Review of Factors Utilized in Preconception Health Behavior Research
Authors: Delissaint Dieula , McKyer E. Lisako J.
Published: April 2011

This systematic review critically synthesizes the literature focusing on factors related to preconception health behaviors (PCHBs) among childbearing age women in the United States, developed countries, and developing countries. Ovid Medline and CINAHL databases were searched for peer-reviewed articles published between 1998 and 2008 relating to PCHB. Six major categories of factors were identified: frequency of alcohol intake prior and during pregnancy, glycemic control/diabetes management, physical activity before and during pregnancy, pregnancy planning behavior, cystic fibrosis carrier screening, and other risk factors. A critical finding of this review is that knowledge, awareness, and beliefs of preconception care do not lead to preconception health practice. Younger preconceptional women and women with children were less likely to engage in PCHB. However, women with advanced postgraduate education were more likely to practice preconception care. There is an urgent need to educate young preconceptional women regarding the importance and benefits of practicing preconception care.
Cultural psychiatry and epidemiology: Researching the means, methods and meanings
Authors: Bhui Kamaldeep
Published: April 2011

This article describes my developing interest in cultural psychiatry. This is both a challenging and yet a privileged opportunity to reflect on my research and clinical work over the last 25 years. I describe cultural and interpersonal influences on my thinking and interests, and the development of my research career moving from health services research of specialist services, to primary care research to public mental health research. Specifically, social and cultural influences on risks and responses to mental illness are discussed, as are pathways to care, the recognition of mental illness, and public health and cultural psychiatry research.
Knowledge and Practice of Post-Exposure Prophylaxis (PEP) against HIV Infection among Health Care Providers in a Tertiary Hospital in Nigeria
Authors: Owolabi Rotimi S. , Alabi Peter , Ajayi Samuel , Daniel Olusoji , Ogundiran Adeniyi , Akande Tanimola M. , Onafowokan and Tunde
Published: April 2011

Objective: To assess the knowledge and practice of post exposure prophylaxis (PEP) against HIV infection among health care providers in University of Abuja Teaching Hospital (UATH). Methods: A cross-sectional survey conducted on 230 health care providers in UATH. Results: Majority (97.0%) of the respondents have heard about PEP, but only a few (30.9%) of them could correctly identify the drugs used and duration of PEP. A third of respondents have had one form of accidental exposure or the other. HIV test was carried out in about two-thirds (64.8%) of the source patients. Thirteen (28.3%) of the source patients were HIV-positive. Of the 13 respondents that were exposed to HIV-positive patients, only 3 (23.1%) received PEP, and these three completed PEP, while majority, 10/13 (76.9%) did not receive PEP in spite of their exposure to HIV-positive sources. Conclusion: The study shows that the knowledge and practice of PEP among health care providers are very poor.
Substance Abuse, Acculturation, and HIV Risk among Caribbean-Born Immigrants in the United States
Authors: Saint-Jean Gilbert , Dévieux Jessy , Malow Robert , Tammara Hayley , Carney Kimberly
Published: April 2011

US immigrants of Caribbean origin are overrepresented in the HIV/AIDS prevalence statistics. Bidirectional travel between the United States and the Caribbean region by providing opportunities for sexual mixing may contribute to these high HIV rates. Caribbean immigrants face further risk because of limited health care access, social isolation, and stigma. Additionally, although substance abuse may not represent a major health issue in their countries of origin, Caribbean immigrants are composed disproportionately of adolescents who are at greatest risk of substance abuse. There is little information on the health care characteristics of these migrants, especially regarding HIV care. This article describes how the social and economic circumstances that surround the lives of people from the Caribbean and the challenges of the acculturation process have placed these individuals at risk of substance abuse and HIV infection. The article draws on findings from the literature and analysis of data from several sources.
Prevalence of Lipodystrophy and Dyslipidemia among Patients with HIV Infection on Generic ART in Rural South India
Authors: Kalyanasundaram Annie Phoebe , Jacob Saramma Mini , Hemalatha Ramachandran , Sivakumar Mampakkam Rajappa
Published: April 2011

As antiretroviral therapy (ART) becomes more available to the HIV-infected population, it is important to determine the prevalence of its long-term complications. In this cross-sectional study, 145 HIV-positive patients on ART, 146 HIV-positive patients not on ART, and 72 HIV-negative individuals visiting the Namakkal District Head Quarters Hospital, Tamil Nadu, India, were recruited from February 2007 to April 2009. Among the patients on ART, the prevalence of lipodystrophy was 60.7%; 22.7% with lipohypertrophy, 51.1% with lipoatrophy, and 22.7% with mixed pattern. The proportion of patients with dyslipidemia was significantly higher in the treatment group when compared to ART-naive and HIV-negative controls ( P = .00). Total duration of ART was significantly associated with lipodystrophy ( P = .04) and dyslipidemia ( P = .01). Also, by logistic regression, abnormal metabolic levels were a risk factor in lipodystrophy ( P = .02). This study highlights the need for development of inexpensive and accessible treatments for the reduction of lipodystrophy.
Meningoencephalitis Due to HIV Replication Despite Plasmatic Viral Control
Authors: Dinh Aurélien , Salomon Jérôme , Du Damien Le , Mathez Dominique , Carlier Robert , Bernard Louis , Truchis Pierre de
Published: April 2011

We report a symptomatic case of HIV replication in CSF (Cerebro Spinal Fluid) despite low plasmatic viral load. The patient, known HIV positive since 3 years, under HAART (Highly Active Antiretroviral therapy), presented an acute meningoencephalitis which was improved by optimization of treatment for a better CNS (Central Nervous System) penetration according to the CHARTER's (CNS HIV Antiretroviral Therapy Effects Research) score. CNS can be considered as a specific compartment for HIV replication and can be involved in acute or chronic neurologic impairment. As showed in this observation, CHARTER score could be helpful to optimize HAART penetration in CNS, but indication and use remain uncertain in current practice.
Outlier detection in hyperspectral imagery using closest distance to center with ellipsoidal multivariate trimming
Authors: Caulk Ryan F , Reyes Kevin B , Bauer Kenneth W
Published: April 2011

In this paper we examine the efficacy of using the closest distance to center algorithm in conjunction with ellipsoidal multivariate trimming (MVT) to find outliers in a hyperspectral image. MVT is applied here as a global anomaly detector on images that are pre-processed into clusters using a technique called X-means. Under the assumption that there are no more than 5% outliers in any given cluster set, we develop a method, based upon principal component analysis pre-processing, to create a flexible threshold for determining the percentage of data to retain with MVT. Using a retention percentage that more adequately reflects the actual number of outlier-free observations allows one to form estimates of the mean and covariance matrix that more effectively decrease the effects of swamping and masking as compared to using a set percentile for retention. These ideas are tested against real and synthetically generated hyperspectral imagery.
From Steamed Bun to Grass Mud Horse: E Gao as alternative political discourse on the Chinese Internet
Authors: Bingchun Meng
Published: April 2011

This article examines e gao (online spoofs) as a popular form of political expression which has recently emerged on the Chinese internet. I first introduce a cultural approach to internet-mediated political communication that emphasizes discursive integration and the mutual constitution of communicative activity and subjectivity. I then discuss how these two dimensions are configured in the specific media ecology in China with regard to the emergence of e gao. I will analyse the political implications of e gao through a close reading of the two most influential cases. Granted that these online spoofs neither qualify as rational debates aiming to achieve consensus nor have produced any visible policy consequences, but they constitute a significant component of civic culture that offers both political criticism and emotional bonding for all participants.
On Monsters and Mercy: Law, Faith, and the Value of Vulnerability
Authors: Stone Andrea
Published: April 2011

Despite the putative secularity of our culture, the reality is that in many contexts current church-state law is not separationist but preferentialist. Hidden preferentialism restricts political membership and participation and promotes an illusion of security, which reifies dangerous demarcations that make for an increasingly insular, fearful, unjust society. Through a consideration of monster theory and a reading of Maryse Condé’s I, Tituba, Black Witch of Salem, this article argues for (1) open acknowledgement of the fluid boundary between sacred and secular, (2) epistemological humility in both and (3) a revitalization of debates about the diminishing value and application of mercy.
Walter Benjamin and the Ethics of Violence
Authors: Kellogg Catherine
Published: April 2011

This article examines Walter Benjamin’s 1921 text, “Critique of Violence” in light of its multiple readings. Specifically, different readings and interpretations of this text have become vital to contemporary discussions of police violence, sovereignty, life in the state of exception, revolution, political theology, and most importantly the question of ethical violence. More specifically, if the context of Benjamin’s own writing was the refusal to kill that marked the end of the First World War and the bloody wake that was left after the failure of the German revolution, a current debate between Judith Butler and Slavoj Žižek concerning an “ethics of non-violence,” considers (among other things) the current situation in Israel/Palestine, and their debate turns on competing readings of Benjamin’s text. As I will show, there are different approaches to politics, to the question of what is to be done, that can be teased out by way of different readings of this small, influential text written almost 90 years ago and it is precisely the contradictory nature of this text, its messianism, its relation to the question of historical fulfillment, its invocation of the biblical injunction against killing (one that places this text in the Jewish philosophical tradition), its understanding of the notion of “mere” guilty life, as well as its use of Georges Sorel’s celebration of the mass proletarian strike, that makes it a lightning rod for different readings of politics, faith and law, and gives it its continued importance.
NVA237, a long-acting muscarinic antagonist, as an emerging therapy for chronic obstructive pulmonary disease
Authors: Vogelmeier Claus , Banerji Donald
Published: April 2011

Bronchodilation with a long-acting muscarinic antagonist (LAMA) or long-acting β2-agonist is central to the management of chronic obstructive pulmonary disease (COPD). Tiotropium, the first LAMA available for use in COPD, has been shown to be an effective bronchodilator and is generally safe and well tolerated. However, tiotropium has limitations that include a high incidence of dry mouth, slow onset of action and, in some studies, a part of the patient population did not achieve clinically significant bronchodilation. It also remains unclear whether tiotropium reduces progressive deterioration of lung function in patients with COPD. An ideal LAMA would provide clinically meaningful bronchodilation, deliver symptom relief, prevent disease progression, improve exercise tolerance and health status, prevent and treat complications and exacerbations and reduce mortality risk. A 24-h duration of action, rapid onset of action and a good safety and tolerability profile are also desirable. The once-daily LAMA, NVA237 (glycopyrronium bromide), may meet some of these characteristics. NVA237 has high selectivity for the muscarinic type-3 (M3) receptor which might potentially result in a higher therapeutic index than tiotropium, which is less selective for M3. Phase II studies showed that NVA237 once daily provides clinically significant 24-h bronchodilation with a rapid onset of action and a favourable safety and tolerability profile. Phase III studies are ongoing that will assess the long-term safety and efficacy of NVA237.
Disease-modifying treatments for Alzheimer’s disease
Authors: Galimberti Daniela , Scarpini Elio
Published: April 2011

The first drugs developed for Alzheimer’s disease (AD), acetylcholinesterase inhibitors (AChEI), increase acetylcholine levels, previously demonstrated to be reduced in AD. To date, four AChEI are approved for the treatment of mild-to-moderate AD. A further therapeutic option available for moderate-to-severe AD is memantine. These treatments are symptomatic, whereas drugs under development are intended to modify the pathological steps leading to AD, thus acting on the evolution of the disease. For this reason they are have been termed ‘disease-modifying’ drugs. To block the progression of the disease they have to interfere with the pathogenic steps responsible for the clinical symptoms, including the deposition of extracellular amyloid beta (Aβ) plaques and of intracellular neurofibrillary tangles, inflammation, oxidative damage, iron deregulation and cholesterol metabolism. In this review, new perspectives will be discussed. In particular, several approaches will be described, including interference with Aβ deposition by anti-Aβ aggregation agents, vaccination, γ-secretase inhibitors or selective Aβ-lowering agents; interference with tau deposition by methylthioninium chloride; and reduction of inflammation and oxidative damage.
Minimal or Massive? The Political Agenda-Setting Power of the Mass Media According to Different Methods
Authors: Van Aelst Peter , Walgrave Stefaan
Published: April 2011

The debate on the media’s agenda-setting power is not settled yet. Most empirical agenda-setting studies using time-series analyses found that the media matter for the political agenda, but the size of the found media effects remains often modest. This nuanced view on media impact seems to contradict with the perceptions of politicians. Our comparative survey of members of parliament in four small parliamentary democracies—Belgium, Netherlands, Sweden, and Denmark—shows that they consider the mass media to be one of the key political agenda setters directly competing with the Prime Minister and the powerful political parties. This article further explores the inconsistency between “objective” and “subjective” findings.We develop six possible explanations for the contradicting findings produced by both methods and formulate concrete suggestions to improve both methods and diminish the gap between them.
Embodied Emotion Perception
Authors: Neal David T. , Chartrand Tanya L.
Published: April 2011

How do we recognize the emotions other people are feeling? One source of information may be facial feedback signals generated when we automatically mimic the expressions displayed on others' faces. Supporting this “embodied emotion perception,” dampening (Experiment 1) and amplifying (Experiment 2) facial feedback signals, respectively, impaired and improved people’s ability to read others' facial emotions. In Experiment 1, emotion perception was significantly impaired in people who had received a cosmetic procedure that reduces muscular feedback from the face (Botox) compared to a procedure that does not reduce feedback (a dermal filler). Experiment 2 capitalized on the fact that feedback signals are enhanced when muscle contractions meet resistance. Accordingly, when the skin was made resistant to underlying muscle contractions via a restricting gel, emotion perception improved, and did so only for emotion judgments that theoretically could benefit from facial feedback.
Methodological challenges when estimating the effects of season and seasonal exposures on birth outcomes
Authors: Strand Linn Beate , Barnett Adrian G , Tong Shilu
Published: April 2011

Background

Many previous studies have found seasonal patterns in birth outcomes, but with little agreement about which season poses the highest risk. Some of the heterogeneity between studies may be explained by a previously unknown bias. The bias occurs in retrospective cohorts which include all births occurring within a fixed start and end date, which means shorter pregnancies are missed at the start of the study, and longer pregnancies are missed at the end. Our objective was to show the potential size of this bias and how to avoid it.

Methods

To demonstrate the bias we simulated a retrospective birth cohort with no seasonal pattern in gestation and used a range of cohort end dates. As a real example, we used a cohort of 114,063 singleton births in Brisbane between 1 July 2005 and 30 June 2009 and examined the bias when estimating changes in gestation length associated with season (using month of conception) and a seasonal exposure (temperature). We used survival analyses with temperature as a time-dependent variable.

Results

We found strong artificial seasonal patterns in gestation length by month of conception, which depended on the end date of the study. The bias was avoided when the day and month of the start date was just before the day and month of the end date (regardless of year), so that the longer gestations at the start of the study were balanced by the shorter gestations at the end. After removing the fixed cohort bias there was a noticeable change in the effect of temperature on gestation length. The adjusted hazard ratios were flatter at the extremes of temperature but steeper between 15 and 25°C.

Conclusions

Studies using retrospective birth cohorts should account for the fixed cohort bias by removing selected births to get unbiased estimates of seasonal health effects.
Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer
Authors: Yeh Chen-Yun , Shin Shin-Mei , Yeh Hsuan-Heng , Wu Tsung-Jung , Shin Jyh-Wei , Chang Tsuey-Yu , Raghavaraju Giri , Lee Chung-Ta , Chiang Jung-Hsien , Tseng Vincent S , Lee Yuan-Chii G , Shen Cheng-Huang , Chow Nan-Haw , Liu Hsiao-Sheng
Published: April 2011

Background

A cross-talk between different receptor tyrosine kinases (RTKs) plays an important role in the pathogenesis of human cancers.

Methods

Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA) silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients.

Results

A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α) with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α in vitro was through a ras- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (p < 0.05), and overexpression of c-Met/Axl/PDGFR-α or c-Met alone showed the most significant correlation with poor survival (p < 0.01).

Conclusions

In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy.
Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo
Authors: Lee Seung Joon , Krauthauser Candice , Maduskuie Victoria , Fawcett Paul T , Olson James M , Rajasekaran Sigrid A
Published: April 2011

Background

Medulloblastoma is the most common brain tumor in children, and its prognosis is worse than for many other common pediatric cancers. Survivors undergoing treatment suffer from serious therapy-related side effects. Thus, it is imperative to identify safer, effective treatments for medulloblastoma. In this study we evaluated the anti-cancer potential of curcumin in medulloblastoma by testing its ability to induce apoptosis and inhibit tumor growthin vitroandin vivousing established medulloblastoma models.

Methods

Using cultured medulloblastoma cells, tumor xenografts, and the Smo/Smo transgenic medulloblastoma mouse model, the antitumor effects of curcumin were testedin vitroandin vivo.

Results

Curcumin induced apoptosis and cell cycle arrest at the G2/M phase in medulloblastoma cells. These effects were accompanied by reduced histone deacetylase (HDAC) 4 expression and activity and increased tubulin acetylation, ultimately leading to mitotic catastrophe. Inin vivomedulloblastoma xenografts, curcumin reduced tumor growth and significantly increased survival in the Smo/Smo transgenic medulloblastoma mouse model.

Conclusions

Thein vitroandin vivodata suggest that curcumin has the potential to be developed as a therapeutic agent for medulloblastoma.
Cross-cultural development of an item list for computer-adaptive testing of fatigue in oncological patients
Authors: Giesinger Johannes M , Aa Petersen Morten , Groenvold Mogens , Aaronson Neil K , Arraras Juan I , Conroy Thierry , Gamper Eva M , Kemmler Georg , King Madeleine T , Oberguggenberger Anne S , Velikova Galina , Young Teresa , Holzner Bernhard ,   the European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC-QLG)
Published: April 2011

Introduction

Within an ongoing project of the EORTC Quality of Life Group, we are developing computerized adaptive test (CAT) measures for the QLQ-C30 scales. These new CAT measures are conceptualised to reflect the same constructs as the QLQ-C30 scales. Accordingly, the Fatigue-CAT is intended to capture physical and general fatigue.

Methods

The EORTC approach to CAT development comprises four phases (literature search, operationalisation, pre-testing, and field testing). Phases I-III are described in detail in this paper. A literature search for fatigue items was performed in major medical databases. After refinement through several expert panels, the remaining items were used as the basis for adapting items and/or formulating new items fitting the EORTC item style. To obtain feedback from patients with cancer, these English items were translated into Danish, French, German, and Spanish and tested in the respective countries.

Results

Based on the literature search a list containing 588 items was generated. After a comprehensive item selection procedure focusing on content, redundancy, item clarity and item difficulty a list of 44 fatigue items was generated. Patient interviews (n = 52) resulted in 12 revisions of wording and translations.

Discussion

The item list developed in phases I-III will be further investigated within a field-testing phase (IV) to examine psychometric characteristics and to fit an item response theory model. The Fatigue CAT based on this item bank will provide scores that are backward-compatible to the original QLQ-C30 fatigue scale.
15 kDa Granulysin versus GM-CSF for monocytes differentiation: analogies and differences at the transcriptome level
Authors: Castiello Luciano , Stroncek David F , Finn Michael W , Wang Ena , Marincola Francesco M , Clayberger Carol , Krensky Alan M , Sabatino Marianna
Published: April 2011

Background

Granulysin is an antimicrobial and proinflammatory protein with several isoforms. While the 9 kDa isoform is a well described cytolytic molecule with pro-inflammatory activity, the functions of the 15 kDa isoform is less well understood. Recently it was shown that 15 kDa Granulysin can act as an alarmin that is able to activate monocytes and immature dendritic cells. Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) is a growth factor widely used in immunotherapy both forin vivoandex vivoapplications, especially for its proliferative effects.

Methods

We analyzed gene expression profiles of monocytes cultured with 15 kDa Granulysin or GM-CSF for 4, 12, 24 and 48 hours to unravel both similarities and differences between the effects of these stimulators.

Results

The analysis revealed a common signature induced by both factors at each time point, but over time, a more specific signature for each factor became evident. At all time points, 15 kDa Granulysin induced immune response, chemotaxis and cell adhesion genes. In addition, only 15 kDa Granulsyin induced the activation of pathways related to fundamental dendritic cell functions, such as co-stimulation of T-cell activation and Th1 development. GM-CSF specifically down-regulated genes related to cell cycle arrest and the immune response. More specifically, cytokine production, lymphocyte mediated immunity and humoral immune response were down-regulated at late time points.

Conclusion

This study provides important insights on the effects of a novel agent, 15 kDa granulysin, that holds promise for therapeutic applications aimed at the activation of the immune response.
Infectious clones of Tomato leaf curl Palampur virus with a defective DNA B and their pseudo-recombination with Tomato leaf curl New Delhi virus
Authors: Malik Aamir Humayun , Briddon Rob W , Mansoor Shahid
Published: April 2011

Background

Tomato leaf curl Palampur virus (ToLCPMV) is a bipartite begomovirus which has been reported from India and Iran but infectious clones have not been obtained. We have previously shown the association of Zucchini yellow mosaic virus (ZYMV), a potyvirus, with severe leaf curl disease of muskmelon in Pakistan. However, the severity of symptoms in the field and yield losses led us to believe that some other agent, such as a begomovirus, could be associated with the disease.

Results

A bipartite begomovirus associated with a severe yellow leaf curl disease on muskmelon in Pakistan has been characterized. Analysis of the complete nucleotide sequence of the DNA A and DNA B components of the begomovirus showed that it has the highest DNA sequence identity with ToLCPMV. However, the gene encoding the nuclear shuttle protein (NSP) was truncated in comparison to previously characterised isolates. Agrobacterium-mediated inoculation of Nicotiana benthamiana with the ToLCPMV clones obtained here did not result in symptoms. However, inoculation of plants with the DNA A component of ToLCPMV and the DNA B component of Tomato leaf curl New Delhi virus (ToLCNDV) lead to systemic infection with leaf curl symptoms. This suggested that the lack of infectivity of the ToLCPMV clones was due to the defect in DNA B. The DNA B of ToLCPMV was able to move systemically when inoculated with DNA A of the either virus. Agro-infiltration of muskmelon with the DNA A and DNA B components of ToLCPMV did not lead to symptomatic infection whereas inoculation with the DNA A with the DNA B of ToLCNDV resulted in a hypersensitive response (HR) along the veins. Additionally, agro-infiltration of muskmelon with a construct for the expression of the NSP gene of ToLCNDV under the control of the cauliflower mosaic virus 35S promoter induced a HR, suggesting that this is the gene causing the HR.

Conclusions

Both ToLCPMV and ZYMV are associated with muskmelon leaf curl disease in Pakistan. However, the ToLCPMV variant identified in association with ZYMV has a defective NSP. The results suggest that a variant with a defective NSP may have been selected for in muskmelon, as this protein is an avirulence determinant in this species, and possibly that infection requires the synergistic interaction with ZYMV.
Masitinib as an adjunct therapy for mild-to-moderate Alzheimer's disease: a randomised, placebo-controlled phase 2 trial
Authors: Piette François , Belmin Joël , Vincent Hélène , Schmidt Nicolas , Pariel Sylvie , Verny Marc , Marquis Caroline , Mely Jean , Hugonot-Diener Laurence , Kinet Jean-Pierre , Dubreuil Patrice , Moussy Alain , Hermine Olivier
Published: April 2011

Introduction

Neuroinflammation is thought to be important in Alzheimer's disease pathogenesis. Mast cells are a key component of the inflammatory network and participate in the regulation of the blood-brain barrier's permeability. Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. As the brain is rich in mast cells, the therapeutic potential of masitinib as an adjunct therapy to standard care was investigated.

Methods

A randomised, placebo-controlled, phase 2 study was performed in patients with mild-to-moderate Alzheimer's disease, receiving masitinib as an adjunct to cholinesterase inhibitor and/or memantine. Patients were randomly assigned to receive masitinib (n = 26) (starting dose of 3 or 6 mg/kg/day) or placebo (n = 8), administered twice daily for 24 weeks. The primary endpoint was change from baseline in the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) to assess cognitive function and the related patient response rate.

Results

The rate of clinically relevant cognitive decline according to the ADAS-Cog response (increase >4 points) after 12 and 24 weeks was significantly lower with masitinib adjunctive treatment compared with placebo (6% vs. 50% for both time points; P = 0.040 and P = 0.046, respectively). Moreover, whilst the placebo treatment arm showed worsening mean ADAS-Cog, Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory, and Mini-Mental State Examination scores, the masitinib treatment arm reported improvements, with statistical significance between treatment arms at week 12 and/or week 24 (respectively, P = 0.016 and 0.030; P = 0.035 and 0.128; and P = 0.047 and 0.031). The mean treatment effect according to change in ADAS-Cog score relative to baseline at weeks 12 and 24 was 6.8 and 7.6, respectively. Adverse events occurred more frequently with masitinib treatment (65% vs. 38% of patients); however, the majority of events were of mild or moderate intensity and transitory. Severe adverse events occurred at a similar frequency in the masitinib and placebo arms (15% vs. 13% of patients, respectively). Masitinib-associated events included gastrointestinal disorders, oedema, and rash.

Conclusions

Masitinib administered as add-on therapy to standard care during 24 weeks was associated with slower cognitive decline in Alzheimer's disease, with an acceptable tolerance profile. Masitinib may therefore represent an innovative avenue of treatment in Alzheimer's disease. This trial provides evidence that may support a larger placebo-controlled investigation.

Trial registration

Clinicaltrials.gov NCT00976118
Analysis of the Wilms' Tumor Suppressor Gene (WT1) in Patients 46,XY Disorders of Sex Development
Authors: Köhler B. , Biebermann H. , Friedsam V. , Gellermann J. , Maier R. F. , Pohl M. , Wieacker P. , Hiort O. , Grüters A. , Krude H.
Published: April 2011

Context:

The Wilms' tumor suppressor gene (WT1) is one of the major regulators of early gonadal and kidney development. WT1 mutations have been identified in 46,XY disorders of sex development (DSD) with associated kidney disease and in few isolated forms of 46,XY DSD.

Objective:

The objective of the study was the evaluation of WT1 mutations in different phenotypes of isolated 46,XY DSD and clinical consequences.

Design:

The design of the study was: 1) sequencing of the WT1 gene in 210 patients with 46,XY DSD from the German DSD network, consisting of 150 males with severe hypospadias (70 without cryptorchidism, 80 with at least one cryptorchid testis), 10 males with vanishing testes syndrome, and 50 raised females with partial to complete 46,XY gonadal dysgenesis; and 2) genotype-phenotype correlation of our and all published patients with 46,XY DSD and WT1 mutations.

Results:

We have detected WT1 mutations in six of 80 patients with severe hypospadias (7.5%) and at least one cryptorchid testis and in one of 10 patients with vanishing testes syndrome (10%). All patients except one developed Wilms' tumor and/or nephropathy in childhood or adolescence.

Conclusion:

WT1 analysis should be performed in newborns with complex hypospadias with at least one cryptorchid testis and in isolated 46,XY partial to complete gonadal dysgenesis. Kidney disease might not develop until later life in these cases. WT1 analysis is mandatory in all 46,XY DSD with associated kidney disease. WT1 analysis is not indicated in newborns with isolated hypospadias without cryptorchidism. Patients with WT1 mutations should be followed up closely because the risk of developing a Wilms' tumor, nephropathy, and/or gonadal tumor is very high.
Divalent cations regulate the folding and activation status of integrins during their intracellular trafficking
Authors: Tiwari Shweta , Askari Janet A. , Humphries Martin J. , Bulleid Neil J.
Published: April 2011

Integrins are divalent cation-dependent, αβ heterodimeric adhesion receptors that control many fundamental aspects of cell behaviour by bi-directional signalling between the extracellular matrix and intracellular cytoskeleton. The activation state of cell surface integrins is tightly regulated by divalent cation occupancy of the ligand-binding pocket and by interaction with cytoplasmic adaptor proteins, such as talin. These agents elicit gross conformational changes across the entire molecule, which specify the activation state. Much less is known about the activation state of newly synthesised integrins or the role of cations during the early folding and trafficking of integrins. Here we use a number of well-characterised, conformation-specific antibodies to demonstrate that β1-integrins adopt the bent, inactive conformation after assembly with α-integrins in the endoplasmic reticulum. Folding and assembly are totally dependent on the binding of Ca2+ ions. In addition, Ca2+ binding prevents integrin activation before its arrival at the cell surface. Activation at the cell surface occurs only following displacement of Ca2+ with Mg2+ or Mn2+. These results demonstrate the essential roles played by divalent cations to facilitate folding of the β-integrin subunit, to prevent inappropriate intracellular integrin signalling, and to activate ligand binding and signalling at the cell surface.