bluuebunny/crossref_metadata_2025 huggingface dataset:
A Prospective Outcome Study of Neonatal Cerebral Sinovenous Thrombosis
Authors: Moharir Mahendranath D. , Shroff Manohar , Pontigon Ann-Marie , Askalan Rand , Yau Ivanna , MacGregor Daune , deVeber Gabrielle A.
Published: June 2011

Neonatal cerebral sinovenous thrombosis is a frequent contributor to neonatal mortality and morbidity. Treatment is controversial, and reported clinical outcomes vary widely. Newborns with radiologically confirmed neonatal cerebral sinovenous thrombosis from 1992 to 2009 were prospectively followed in our Children’s Stroke Clinic for standardized outcomes, including the Pediatric Stroke Outcome Measure. Outcomes were available in 90 of 104 (87%) neonates. Early outcomes included cerebral sinovenous thrombosis-associated death (5) and thrombus propagation (15 [6 associated with new venous infarcts]). Lack of anticoagulation predicted propagation (RR = 13; P = .0007). Complete thrombus recanalization occurred in 90% by 3 months. Late outcomes (median, 2.5 years) were epilepsy (15) and neurological disability (50), which included moderate-severe language (43), sensorimotor (38), and cognitive/behavioral (24) deficits. Overall, 61% had poor outcome (death/any deficit). Concurrent neurological comorbidity at diagnosis (odds ratio = 2.8; P = .029) predicted poor outcome. Clinical trials are urgently needed to establish more effective treatment strategies.
Cellular Mechanisms of Neurovascular Damage and Repair After Stroke
Authors: Arai Ken , Lok Josephine , Guo Shuzhen , Hayakawa Kazuhide , Xing Changhong , Lo Eng H.
Published: June 2011

The biological processes underlying stroke are complex, and patients have a narrow repertoire of therapeutic opportunities. After the National Institutes of Health (NIH) convened the Stroke Progress Review Group in 2001, stroke research shifted from having a purely neurocentric focus to adopting a more integrated view wherein dynamic interactions between all cell types contribute to function and dysfunction in the brain. This so-called “neurovascular unit” provides a conceptual framework that emphasizes cell–cell interactions between neuronal, glial, and vascular elements. Under normal conditions, signaling within the neurovascular unit helps maintain homeostasis. After stroke, cell–cell signaling is disturbed, leading to pathophysiology. More recently, emerging data now suggest that these cell–cell signaling mechanisms may also mediate parallel processes of neurovascular remodeling during stroke recovery. Because plasticity is a signature feature of the young and developing brain, these concepts may have special relevance to how the pediatric brain responds after stroke.
Body Mass Index and Long-Term Mortality in an Elderly Mediterranean Population
Authors: Zunzunegui Maria Victoria , Sanchez Maria Teresa , Garcia Angela , Ribera Casado Jose Manuel , Otero Angel
Published: June 2011

Objectives: To describe the relationship of body mass index and mortality in older adults, examining the influence of sex and cardiovascular morbidity. Methods: Sixteen-year cohort of a population sample of 1,008 people aged 65 and over. BMI mortality hazard ratios are estimated controlling for age, sex, education, physical activity, smoking, chronic conditions, and ADL (activities of daily living) disability. Results: At baseline the median BMI is 26.8 (Interquartile range: 24.2-29.7 Kg/m2). Findings show that during 16 years there were 672 deaths. The U-shaped curve of the mortality hazard by BMI is wide. The minimum mortality occur at BMI = 30.5 Kg/m2. Findings show that men had lower mortality risk with increasing BMI and that cardiovascular disease was associated with high mortality in the low-BMI category. Discussion: Underweight is a risk factor for mortality among elderly people, whereas overweight and mild obesity are associated with the lowest mortality particularly among men and those with cardiovascular morbidity.
Surplus Distribution in Microfinance
Authors: Périlleux Anaïs , Hudon Marek , Bloy Eddy
Published: June 2011

How do microfinance institutions (MFIs) allocate their surplus to stakeholders? This article shows that this allocation process varies depending on the MFI ownership structure. Nonprofit organizations and shareholders-held MFIs exhibit a tendency to largely keep their surplus within the MFI as a self-financing margin (reserve accounts, future investments, and capital increase) rather than transferring it to their clients (interest rate decrease) and their employees (salary increase). The surplus distribution in COOPs is more in favor of providers and employees. Finally, the article discusses the importance of these findings for the evaluation of MFIs by policy makers.
Dynamic mechanical properties of polysiloxane-modified, castor oil-based polyurethane/epoxy interpenetrating polymer network composites
Authors: Chen Shoubing , Wang Qihua , Wang Tingmei
Published: June 2011

A series of hydroxyl-terminated poly dimethyl siloxane (HTPDMS)-modified polyurethane (PU)/epoxy resin (EP) graft interpenetrating polymer network (IPN) composites were prepared. The morphologies of impact fracture surfaces, tensile and impact strengths, damping properties as well as thermal stability properties of the HTPDMS modified IPN composites were studied systematically. The results revealed that the impact strength of the IPN composites could be significantly improved after the incorporation of HTPDMS, whereas the tensile strength of the composites was impaired when the HTPDMS content were more than 5%. The studies also showed that the addition of HTPDMS can improve the damping properties of pure PU/EP IPN and can improve the thermal decomposition temperature. It is expected that the modified IPN composites may be used as structural damping materials.
Colouring in the “black-box”: Alternative renderings of scientific visualisations in two comic book cosmologies
Authors: Locke Simon
Published: June 2011

Two somewhat contrasting views of public uses of scientific visualisations argue that they are “black-boxed” with meaning given by the scientific community or they are “polysemic” with meaning given by the context of presentation. This paper argues that whether they are treated as black-boxed or not and in what manner this is done is itself part of the meaning given by context. Thus, “black-boxing” is done not only by scientists but also by members of the public. The argument is illustrated by reference to two recent comic books, Dave Sim’s Cerebus and Alan Moore’s Promethea, in which the authors present cosmological visions of the universe using scientific visualisations to create a sense of realism. From analysis of their use of images of planet Earth and the human foetus it is argued that, although the images are black-boxed, the authors re-work them aesthetically to suit their specific moral and cosmological views.
Supporting Work Effort of SSDI Beneficiaries
Authors: Chambless Catherine E. , Julnes George , McCormick Sara T. , Reither Anne
Published: June 2011

Few SSDI (Social Security Disability Insurance) beneficiaries in the United States ever increase earnings to the point of leaving SSDI, a source of growing concern both because of the costs of the program and because some beneficiaries can feel trapped in relative poverty by the need to retain SSDI benefits. One barrier to exit is the “cash cliff,” the abrupt loss of monthly benefits once earnings rise beyond the limits for eligibility. A four-state random assignment policy experiment was funded by the Social Security Administration (SSA) to explore implementation of a gradual reduction of cash benefits as earnings rise (i.e., the “benefit offset”). The project in Utah, one of the four states, found positive impacts of the policy on employment outcomes for certain groups of participants. More important, however, were the lessons learned in Utah for implementing policy initiatives with vulnerable populations such as those with disabilities. These lessons learned are in the areas of partnering among service agencies, enhancing communication, and implementing policy innovations in complex policy environments.
Predicting Seasonal Influenza Vaccination Among Hospital-Based Nurses
Authors: Marentette Theresa , El-Masri Maher M.
Published: June 2011

A descriptive cross-sectional online survey of a convenience sample of 202 hospital-based nurses was conducted to explore the factors associated with influenza vaccination. The findings suggest that the independent predictors of influenza vaccination were perception of job as a risk increasing factor (OR = 12.14; 95% CI [1.89, 78.08]), workplace vaccination clinics and campaigns (OR = 2.88; 95% CI [1.12, 7.38]), vaccination in the previous season (OR = 34.80; 95% CI [12.99, 93.28]), viewing vaccination as an inconvenience (OR = 0.22; 95% CI [0.07, 0.67]), and one’s belief that the immune system provides better protection than the vaccine (OR = 0.29; 95% CI [0.11, 0.77]). In conclusion, the findings support the existing literature with regards to low vaccination rates among health care providers. Furthermore, the identification of the predictors of influenza vaccination among nurses may assist administrators and policy makers with the implementation of evidence-based vaccination strategies.
Climate Proofing Infrastructure in Bangladesh: The Incremental Cost of Limiting Future Flood Damage
Authors: Dasgupta Susmita , Huq Mainul , Zahirul Huq Khan  , Sohel Masud Md. , Manjur Murshed Zahid Ahmed  , Mukherjee Nandan , Pandey Kiran
Published: June 2011

Bangladesh is one of the most flood prone countries in the world. Two thirds of the country is less than 5 m above sea level. Past monsoon flood records indicate that about 21% of the country is subject to annual flooding and an additional 42% is at risk of floods with varied intensity. Although annual regular flooding has traditionally been beneficial, providing nutrient-laden sediments and recharging groundwater aquifers, the country often experiences severe flooding during a monsoon that causes significant damage to crops and properties with adverse impacts on rural livelihoods and production. The 1998 flood inundated two thirds of the land area, resulting in damages and losses of over US$2 billion, or 4.8% of GDP. Climate models suggest increased precipitation, higher transboundary water flows, and sea-level rise will all increase the destructive power of monsoon floods. Using climate change scenarios out to 2050, hydrological and hydrodynamic models, this article estimates an incremental cost to climate-proof roads and railways, river embankments protecting productive agricultural lands, and drainage systems and erosion control measures for major towns of US$2,671 million initially and US$54 million in annual recurrent costs.
The Social Justice Roots of the Mentors in Violence Prevention Model and Its Application in a High School Setting
Authors: Katz Jackson , Heisterkamp H. Alan , Fleming Wm. Michael
Published: June 2011

The social justice roots and theory of the Mentors in Violence Prevention (MVP) model is presented, followed by an empirical study examining the influence of MVP in high school settings. Findings reveal students exposed to the MVP model are more likely to see forms of violence as being wrong and are more likely to take actions to intervene than students not exposed to the program. Findings support the premises on which MVP is founded.
Correlates of Adherence to a Telephone-Based Multiple Health Behavior Change Cancer Preventive Intervention for Teens
Authors: Mays Darren , Peshkin Beth N. , Sharff McKane E. , Walker Leslie R. , Abraham Anisha A. , Hawkins Kirsten B. , Tercyak Kenneth P.
Published: June 2011

This study examined factors associated with teens’ adherence to a multiple health behavior cancer preventive intervention. Analyses identified predictors of trial enrollment, run-in completion, and adherence (intervention initiation, number of sessions completed). Of 104 teens screened, 73% ( n = 76) were trial eligible. White teens were more likely to enroll than non-Whites (χ2[1] df = 4.49, p = .04). Among enrolled teens, 76% ( n = 50) completed the run-in; there were no differences between run-in completers and noncompleters. A majority of run-in completers (70%, n = 35) initiated the intervention, though teens who initiated the intervention were significantly younger than those who did not ( p < .05). The mean number of sessions completed was 5.7 ( SD = 2.6; maximum = 8). After adjusting for age, teens with poorer session engagement (e.g., less cooperative) completed fewer sessions (B = −1.97, p = .003, R2 = .24). Implications for adolescent cancer prevention research are discussed.
The Life and Form of the City: An Interview with Bill Hillier
Authors: Westin Sara
Published: June 2011

What are the relations between urban form and social and economic processes in the city? Or more importantly: How can we come to terms with these relations? These questions — fundamental not only for social scientists across the disciplines, but indeed also for architectural theorists — make up the underlying themes of this interview with Bill Hillier, professor of Architectural and Urban Morphology, Bartlett School, University College London. The interview was conducted at his office in the spring of 2008 and the purpose was to discuss Professor Hillier’s ideas on space, urbanity and the theory of space syntax put forward in his well-known book Space is the Machine from 1996. The conversation also provides interesting insights into Professor Hillier’s thoughts on the relation between the human mind and her material surroundings.
Disclaimers, dichotomies and disappearances in international business textbooks: A postcolonial deconstruction
Authors: Fougère Martin , Moulettes Agneta
Published: June 2011

In this article, we draw on a postcolonial sensibility to deconstruct how culture is discussed in mainstream international business textbooks. Through this deconstruction we show: (1) how the initial disclaimers that call for cultural sensitivity can be seen as pointing to the opposite of what they claim, which leads us to question the cultural sensitivity notion from ethical and political standpoints; (2) how the cultural dichotomies that form the core of the discussions always tend to silence the suppressed ‘other’ features on each side, which leads us to point to the much more ambivalent nature of culture and the hybrid spaces that can be created through cultural translation; (3) how (colonial) history is conspicuously absent from the arguments about ‘cultural’ underdevelopment and thus haunts the text. We conclude the article by suggesting the development of alternative types of international business textbook material on culture.
Speaking and remembering in one or two languages: bilingual vs. monolingual lexicalization and memory for motion events
Authors: Filipović Luna
Published: June 2011

The aim of this study is to test whether balanced English–Spanish bilingual speakers behave like monolinguals in each of their languages when describing and remembering complex motion events. The semantic domain in question is motion, because some components (namely the manner of motion) are more difficult to lexicalize in Spanish than in English because of typological constraints (see Filipović, 2007; Slobin, 1996, 1997; Talmy, 1985). As a result, performance on a recognition task involving motion verbs could be expected to vary depending on the language used in the experiment. English and Spanish monolinguals and bilinguals performed the recognition task. Results from the monolinguals indicate that there is a language effect based on this typological difference. Specifically, English monolingual speakers performed significantly better than their Spanish peers in the recognition task in both of our conditions, i.e., with verbalization and without verbalization. The bilingual results on the other hand strongly suggest that these speakers tend to adhere to a single lexicalization pattern that is acceptable in both languages, which is the Spanish one in this case. We discuss further implications of these results for language processing and for memory of motion events in general.
Chinese meets Malay meets English: origins of Singaporean English word-final high tone
Authors: Ng E-Ching
Published: June 2011

This article investigates the origins of the word-final high tone in Chinese speakers’ Colloquial Singaporean English (CSE). Uniquely among Chinese Englishes, high tone is not attracted to stress, but to word-final position, e.g., hiˈ biscus [LˈMH]. Since this tonal pattern has no convincing match in Singapore’s major Chinese varieties, the author proposes that its ultimate source is indigenous Malay speakers’ phrase-final intonational rise. New recordings provide evidence for transfer via the formerly widespread Malay-based pidgin known as Bazaar Malay, reinforced by the Baba Malay creole of earlier Chinese settlers as well as Indian English. This proposed path of transmission from indigenous Malay > Bazaar Malay > Chinese CSE begs two questions: why did transfer occur from a non-native language, and why did the final high boundary tone become more frequent with each transfer? The author discusses these issues in the light of findings from SLA, third language acquisition, and creole studies, which show that the emergence of this highly marked feature was in fact favoured by a number of known constraints on transfer. Thus CSE tone provides not only a test case for rigorous investigation within a highly multilingual context, but also appears to constitute the first documented case of L2 to L3 prosodic transfer.
Ambient affiliation: A linguistic perspective on Twitter
Authors: Zappavigna Michele
Published: June 2011

This article explores how language is used to build community with the microblogging service, Twitter (www.twitter.com). Systemic Functional Linguistic (SFL), a theory of language use in its social context, is employed to analyse the structure and meaning of ‘tweets’ (posts to Twitter) in a corpus of 45,000 tweets collected in the 24 hours after the announcement of Barak Obama’s victory in the 2008 US presidential elections. This analysis examines the evaluative language used to affiliate in tweets. The article shows how a typographic convention, the hashtag, has extended its meaning potential to operate as a linguistic marker referencing the target of evaluation in a tweet (e.g. #Obama). This both renders the language searchable and is used to upscale the call to affiliate with values expressed in the tweet. We are currently witnessing a cultural shift in electronic discourse from online conversation to such ‘searchable talk’.
The niches of interpersonal media: Relationships in time and space
Authors: Dimmick John , Feaster John Christian , Ramirez Artemio
Published: June 2011

According to the theory of the niche, media must differentiate themselves along resource dimensions that allow for their survival to compete and coexist within a resource space. Within this study, contacts with personal relationships are framed as a key resource domain over which channels of interpersonal communication (interpersonal media) compete to occupy niches within the resource spaces of social networks. One hundred and forty-two college undergraduates completed a time/space diary for a randomly assigned weekday in which they recorded their contacts or ‘bundles’ with members of their personal social network. Analysis of the data shows that interpersonal media coexist because they are differentiated from each other in the contacts they allow with different relationships at different times and locations. Although evidence is found regarding heavy competition among the media under analysis, each is used in different time/space/network relationship contexts.
Long-term exercise attenuates blood pressure responsiveness and modulates kidney angiotensin II signalling and urinary sodium excretion in SHR
Authors: Ciampone Silmara , Borges Rafael , de Lima Ize P , Mesquita Flávia F , Cambiucci Elizabeth C , Gontijo José AR
Published: June 2011

Observations have been made regarding the effects of long-term exercise training on blood pressure, renal sodium handling and renal renin–angiotensin–aldosterone (RAS) intracellular pathways in conscious, trained Okamoto–Aoki spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKy) normotensive rats, compared with appropriate age-matched sedentary SHR and WKy. To evaluate the influence of exercise training on renal function and RAS, receptors and intracellular angiotensin II (AngII) pathway compounds were used respectively, and lithium clearance and western blot methods were utilised. The current study demonstrated that increased blood pressure in SHR was blunted and significantly reduced by long-term swim training between the ages of 6 and 16 weeks. Additionally, the investigators observed an increased fractional urinary sodium excretion in trained SHR (SHRT) rats, compared with sedentary SHR (SHRS), despite a significantly decreased creatinine clearance (CCr). Furthermore, immunoblotting analysis demonstrated a decreased expression of AT1R in the entire kidney of TSHR rats, compared with SSHR. Conversely, the expression of the AT2R, in both sedentary and trained SHR, was unchanged. The present study may indicate that, in the kidney, long-term exercise exerts a modulating effect on AngII receptor expression. In fact, the present study indicates an association of increasing natriuresis, reciprocal changes in renal AngII receptors and intracellular pathway proteins with the fall in blood pressure levels observed in TSHR rats compared with age-matched SSHR rats.
Aliskiren reduces prorenin receptor expression and activity in cultured human aortic smooth muscle cells
Authors: Ferri Nicola , Greco Carolina Magdalen , Maiocchi Giuseppe , Corsini Alberto
Published: June 2011

Introduction: The recent discovery of a specific receptor for renin/prorenin (PRR) has added new interest to the potential pharmacological actions of aliskiren, the first direct renin inhibitor.

Materials and methods: In the present study, to gain new insights into the pharmacological properties of aliskiren, we investigated the effect of aliskiren on PRR expression and activity in cultured human smooth muscle cells (HSMCs).

Results: Co-incubation of HSMCs with angiotensinogen (ANG) (1.5× 10-7M) and prorenin (10-8–10-7M) resulted in an efficient production (within 4h) of angiotensin I, almost completely inhibited by 10-5M aliskiren (-86.0 ± 14.0%). In HSMCs stimulated with both ANG and prorenin, a 24h incubation with aliskiren (10-6–10-5M) resulted in a concentration-dependent reduction of PRR mRNA levels (IC50 4.6 × 10-6M). The cell surface expression of PRR determined by flow cytometry analysis was also reduced after incubation with aliskiren in a concentration-dependent manner. The lower levels of PRR were associated with a reduced expression of TGF-β, PAI-1 and type I collagen mRNA.

Conclusions: These results suggest a direct pharmacological action of aliskiren on PRR expression and its signalling pathway in HSMCs. This reported action of aliskiren may reveal a new scenario of the pharmacological properties of aliskiren.
Intertextuality in Old Testament Research
Authors: Miller Geoffrey D.
Published: June 2011

All biblical scholars are familiar with the term ‘intertextuality’, but few can agree on the nature of the concept or how readers should identify intertextual relationships among texts. Some scholars employ a purely synchronic approach when reading texts together, emphasizing the autonomy of the reader in attributing meaning to textual connections. Other scholars pursue a more diachronic approach, seeking to uncover the specific links to precursor texts that the author wants readers to perceive. Within and between these two groups, disagreements also persist over how to differentiate legitimate intertextual connections from coincidental similarities, as well as how to exegete interrelated texts in light of their connections. This article surveys literature from the past twenty years that aims to answer these questions. None of these answers have brought about consensus, and perhaps the best solution is to label some of these studies by a name other than ‘intertextuality’.
The Gospel of Peter: Directions and Issues in Contemporary Research
Authors: Foster Paul
Published: June 2011

Following a period of virtual neglect, interest in the Gospel of Peter has blossomed over the last three to four decades. In part this reflects the wider phenomenon of increased study of non-canonical texts, but more specifically this is also related to various theories that have suggested that traditions in this text may pre-date the forms of parallel traditions found in the canonical gospels. This article surveys three major issues that have surrounded the Gospel of Peter. These are: (i) its relationship to the canonical gospels; (ii) the identification of other fragmentary texts as manuscript witnesses to the text; (iii) the Christology and wider theological profile of the text.
The Identity of Jesus in the Gospel of Mark: Past and Present Proposals
Authors: Johansson Daniel
Published: June 2011

Focusing on the question whether the Markan Jesus is viewed as a divine figure or a merely human being, this article surveys the various interpretations of the Christology of the Gospel of Mark from the late nineteenth century to the present date. Three broad periods are detected. The first is characterized by a combination of a low Christology with a high estimation of Mark as history. After the publication of Wrede’s Messiasgeheimnis this changes, and for various reasons the majority of scholars view Mark’s Jesus as a superhuman being. A new shift takes place around 1970 when the Markan Jesus again is seen as a merely human being. While this still remains the majority position there is far from a consensus in this regard, and present Markan scholarship seems to be more divided than ever before.
Religious Experience in New Testament Research
Authors: Batluck Mark
Published: June 2011

Initiated by Gunkel in 1888, and again by Dunn in 1970, research on religious experience in the New Testament has developed into four distinct streams, all of which address the matter from a different vantage point. Mystical/revelatory experience examines early Christian texts that are ecstatic or disclose new information to the recipient. A second group equates religious experience with encounters of the Holy Spirit.Thirdly, historical Jesus studies investigates historical dimensions of the religious experience described in the Gospels. Fourthly, others address religious experience categorically, trying to account for the grand scope and effect of religious experience recorded in the writings of the New Testament. Each approach offers a great deal to scholars and will be a fruitful line of inquiry in studies to come.
Major League Baseball Attendance and the Role of Fantasy Baseball
Authors: Nesbit Todd M. , King-Adzima Kerry A.
Published: June 2011

Many explanations exist for the resurgence of the Major League Baseball (MLB) fan base following the 1994-1995 strike. The most prevalent explanations include the 1998 McGuire-Sosa homerun race and Cal Ripken Jr.’s consecutive games record. While such explanations certainly impacted fan interest in the sport, it is remiss to ignore the impact of online fantasy baseball leagues, which surfaced in 1997. This article examines the extent to which participating in a fantasy baseball league influences the MLB game attendance. The results strongly suggest that fantasy baseball participation positively influences MLB game attendance.
The Impact of Hospital Volume on the Development of Infectious Complications After Elective Abdominal Aortic Surgery in the Medicare Population
Authors: Vogel Todd R. , Dombrovskiy Viktor Y. , Graham Alan M. , Lowry Stephen F.
Published: June 2011

Objective: A relationship exists between higher hospital volume and lower mortality, yet the impact of hospital volume on infectious complications after elective abdominal aortic aneurysm (AAA) repair is unknown. Methods: The Medicare database (2005-2007) was utilized. Top 10% for volume were categorized as high-volume (HV) and compared to low-volume (LV) centers for infectious complications and utilization. Results: A total of 42 155 endovascular aneurysm repair (EVAR) and 17 210 open AAA were identified. Mortality in HV was significantly lower than in LV after EVAR and open AAA. After EVAR, HV had lower than LV rates of overall infection (3.10% vs 3.51%; P = .021), PNA (0.94% vs 1.27%, P = .002), and sepsis (0.31% vs 0.45%; P = .03). Length of stay (LOS) and total hospital charges were significantly lower at HV compared to LV after both EVAR and open AAA. Conclusion: For Medicare beneficiaries, undergoing elective AAA repair at hospitals performing higher volume significantly reduced postoperative infectious complications and hospital resource utilization. Further analysis identifying systematic reasons for disparities may offer cost savings and improve outcomes.
Hypoglycaemia is more frequent in type 2 diabetic patients with co-morbid vascular disease: an analysis of the DiaRegis registry
Authors: Gitt Anselm K , Bramlage Peter , Binz Christiane , Krekler Michael , Plate Tanja , Deeg Evelin , Tschöpe Diethelm ,   (for the DiaRegis Study Group)
Published: June 2011

Background: Patients with type-2 diabetes are at risk for treatment- and disease-related complications. Little is known about the interrelation of hypoglycaemia and co-morbid vascular disease (VD), defined as coronary heart disease, stroke and peripheral arterial disease.

Hypothesis: Hypoglycaemia is associated with co-morbid VD in diabetic patients.

Methods: DiaRegis is a prospective registry that included patients with type-2 diabetes in 2009/2010. Metric variables are displayed as median and quartiles. For the comparison of patients with or without VD Odds Ratios (OR) were determined from univariate analyses and adjusted for differences in patient characteristics (multivariable analysis).

Results: Data on hypoglycaemia and VD within the last 12 months were available for 3741 patients (98.2%) with a median (IQR) age of 65.9 (57.6–72.9) years; 46.7% were female. VD patients ( n = 909; 24.3%) were older (70.7 vs 63.9 years; p < 0.0001), less often female (33.6% vs 50.9%; p < 0.0001) and had had diabetes for a longer duration (6.4 vs 5.4 years; p < 0.0001). Mean cholesterol (total, HDL and LDL) was also slightly lower ( p < 0.0001). Glycaemic control (HbA1c, fasting and postprandial glucose) was comparable. VD patients received less metformin (80.7 vs 85.2%; p < 0.01) and more sulfonylureas (31.8 vs 27.6%; p < 0.05). There was an increased incidence of symptomatic hypoglycaemia with or without requiring help and with a need for medical assistance. After adjusting a number of baseline variables the rates of symptomatic hypoglycaemias with help remained significantly increased (OR 3.73 (95% CI 1.31–10.65) in patients with VD.

Conclusions: As hypothesized there is a strong association between the incidence of hypoglycaemia and vascular disease at comparable glycaemic control, which confirms prior randomized controlled trial data suggesting an interrelationship between hypoglycaemia and vascular disease.
Individuation Motivation and Face Experience Can Operate Jointly to Produce the Own-Race Bias
Authors: Young Steven G. , Hugenberg Kurt
Published: June 2011

The own-race bias (ORB) is the tendency for perceivers to better recognize own-race than cross-race (CR) faces. Perceptual approaches to understanding this effect suggest that perceivers typically have low levels of processing experience with CR faces, resulting in poor recognition memory. However, social–cognitive models have demonstrated that perceiver motivation can also influence CR recognition accuracy. The current work bridges these two literatures by exploring how participants' CR experience might facilitate the ability to recognize CR faces when combined with perceiver motivation. In Experiment 1, we demonstrate that motivation translates into superior CR recognition only for perceivers who have relatively extensive prior experience with individuating CR faces. In Experiment 2, we find that a lack of experience with CR faces can be overcome in situations where perceivers are highly motivated to individuate CR faces.
Aripiprazole use combined with depot antipsychotic medication: two cases demonstrating its ability to reduce prolactin levels in an adolescent forensic hospital
Authors: Hill Simon A. , Khan Al Aditya , Wetherill Marion
Published: June 2011

Many patients maintained on depot medication have raised prolactin levels, which can lead to a range of long-term medical problems. The addition of aripiprazole can reduce prolactin levels and restore sexual function in these patients. The cases described demonstrate the potential role of aripiprazole in a forensic setting.
Vilazodone: a brief pharmacological and clinical review of the novel serotonin partial agonist and reuptake inhibitor
Authors: Schwartz Thomas L. , Siddiqui Umar A. , Stahl Stephen M.
Published: June 2011

Background: Vilazodone is the latest US Food and Drug Administration approved antidepressant agent available in the USA. Its putative mechanism of antidepressant action enhances the release of serotonin across the brain’s serotonergic pathways specifically by inhibiting the serotonin transporter, similar to a selective serotonin reuptake inhibitor (SSRI), and simultaneously stimulating serotonin-1a receptors via partial agonism, similar to the anxiolytic buspirone. This combined activity in the single vilazodone agent has been termed by the authors as being a serotonin partial agonist and reuptake inhibitor or (SPARI).

Methods: A MEDLINE and Internet search was conducted and the resultant preclinical and clinical evidence was reviewed . The authors attempt to review laboratory data, animal model data and human trial data to develop a translational theory on the mechanism of antidepressant action of this agent and also its adverse effect potential.

Results: Randomized, controlled empirical data for vilazodone have gained it approval for treating major depressive disorder. It combines two well known pharmacodynamic mechanisms of serotonergic action into a novel agent. Although no head-to-head studies against other antidepressants have been published, the efficacy data for vilazodone appear comparable to other known antidepressants, with similar gastrointestinal side effects to SSRI or serotonin norepinephrine reuptake inhibitor (SNRI) antidepressants, but possibly with a lower incidence of sexual side effects and weight gain.

Discussion: Vilazodone will lend itself to the current armamentarium in the treatment of major depressive disorder and may hold promise for patients who cannot tolerate other antidepressants. Its unique SPARI mechanism of action could also be efficacious for patients who do not respond to SSRI or SNRI antidepressant monotherapies.
RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG
Authors: Yuan Lei , Sacharidou Anastasia , Stratman Amber N. , Le Bras Alexandra , Zwiers Peter J. , Spokes Katherine , Bhasin Manoj , Shih Shou-ching , Nagy Janice A. , Molema Grietje , Aird William C. , Davis George E. , Oettgen Peter
Published: June 2011

ERG is a member of the ETS transcription factor family that is highly enriched in endothelial cells (ECs). To further define the role of ERG in regulating EC function, we evaluated the effect of ERG knock-down on EC lumen formation in 3D collagen matrices. Blockade of ERG using siRNA completely interferes with EC lumen formation. Quantitative PCR (QPCR) was used to identify potential downstream gene targets of ERG. In particular, we identified RhoJ as the Rho GTPase family member that is closely related to Cdc42 as a target of ERG. Knockdown of ERG expression in ECs led to a 75% reduction in the expression of RhoJ. Chromatin immunoprecipitation and transactivation studies demonstrated that ERG could bind to functional sites in the proximal promoter of the RhoJ gene. Knock-down of RhoJ similarly resulted in a marked reduction in the ability of ECs to form lumens. Suppression of either ERG or RhoJ during EC lumen formation was associated with a marked increase in RhoA activation and a decrease in Rac1 and Cdc42 activation and their downstream effectors. Finally, in contrast to other Rho GTPases, RhoJ exhibits a highly EC-restricted expression pattern in several different tissues, including the brain, heart, lung, and liver.
Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up
Authors: Cappellini M. Domenica , Bejaoui Mohamed , Agaoglu Leyla , Canatan Duran , Capra Marcello , Cohen Alan , Drelichman Guillermo , Economou Marina , Fattoum Slaheddine , Kattamis Antonis , Kilinc Yurdanur , Perrotta Silverio , Piga Antonio , Porter John B. , Griffel Louis , Dong Victor , Clark Joan , Aydinok Yesim
Published: June 2011

Patients with β-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged ≥ 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received ≥ 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with ≥ 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ± 11.2 mg Fe/g dry weight (dw; n = 103; P < .001) and 3.1 ± 7.9 mg Fe/g dw (n = 68; P < .001) in the deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n = 196; P < .001) and 371 ng/mL (n = 147; P < .001), respectively, after ≥ 4 years' exposure. Investigator-assessed, drug-related adverse events, including increased blood creatinine (11.2%), abdominal pain (9.0%), and nausea (7.4%), were generally mild to moderate, transient, and reduced in frequency over time. No adverse effect was observed on pediatric growth or adolescent sexual development. This first prospective study of long-term deferasirox use in pediatric and adult patients with β-thalassemia suggests treatment for ≤ 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials.gov as #NCT00171210.
Neurexophilin 1 suppresses the proliferation of hematopoietic progenitor cells
Authors: Kinzfogl John , Hangoc Giao , Broxmeyer Hal E.
Published: June 2011

Neurexin I α (NRXN1α) and Dystroglycan (DAG1) are membrane receptors which serve as mutual ligands in the neuronal system. Neurexophilins (NXPHs) bind NRXN1α. NRXN1α was expressed in primitive populations in human CB (huCB) and murine BM (muBM). DAG1 is ubiquitously expressed in hematopoietic tissue; however, osteoblasts appear to be sites of very high expression within muBM. High concentrations of NXPH were found in huCB plasma and murine lineage-positive splenocytes. We evaluated effects of these molecules on huCB and muBM hematopoietic progenitor cells (HPCs) and HSCs. At both a single and population cell level in vitro, we found that NXPH1 was a potent inhibitor of HPC proliferation acting through NRXN1α an effect down-modulated by DAG1. Injection of recombinant NXPH1 in vivo resulted in myelo- and lymphosuppression in the BM, with absolute numbers and cycling status of functional and phenotypically defined HPCs dose- and time-dependently decreased. Competitive HSC transplantations showed no change in the long-term repopulating activity of HSCs from mice exposed to recombinant NXPH1. These results demonstrate the presence and function of a regulated signaling axis in hematopoiesis centered on NRXN1α and its modulation by DAG1 and NXPH1.
Modeling the evolution of ETV6-RUNX1–induced B-cell precursor acute lymphoblastic leukemia in mice
Authors: van der Weyden Louise , Giotopoulos George , Rust Alistair G. , Matheson Louise S. , van Delft Frederik W. , Kong Jun , Corcoran Anne E. , Greaves Mel F. , Mullighan Charles G. , Huntly Brian J. , Adams David J.
Published: June 2011

The t(12;21) translocation that generates the ETV6-RUNX1 (TEL-AML1) fusion gene, is the most common chromosomal rearrangement in childhood cancer and is exclusively associated with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The translocation arises in utero and is necessary but insufficient for the development of leukemia. Single-nucleotide polymorphism array analysis of ETV6-RUNX1 patient samples has identified multiple additional genetic alterations; however, the role of these lesions in leukemogenesis remains undetermined. Moreover, murine models of ETV6-RUNX1 ALL that faithfully recapitulate the human disease are lacking. To identify novel genes that cooperate with ETV6-RUNX1 in leukemogenesis, we generated a mouse model that uses the endogenous Etv6 locus to coexpress the Etv6-RUNX1 fusion and Sleeping Beauty transposase. An insertional mutagenesis screen was performed by intercrossing these mice with those carrying a Sleeping Beauty transposon array. In contrast to previous models, a substantial proportion (20%) of the offspring developed BCP-ALL. Isolation of the transposon insertion sites identified genes known to be associated with BCP-ALL, including Ebf1 and Epor, in addition to other novel candidates. This is the first mouse model of ETV6-RUNX1 to develop BCP-ALL and provides important insight into the cooperating genetic alterations in ETV6-RUNX1 leukemia.
Reprogramming of EBV-immortalized B-lymphocyte cell lines into induced pluripotent stem cells
Authors: Choi Su Mi , Liu Hua , Chaudhari Pooja , Kim Yonghak , Cheng Linzhao , Feng Jian , Sharkis Saul , Ye Zhaohui , Jang Yoon-Young
Published: June 2011

EBV-immortalized B lymphocyte cell lines have been widely banked for studying a variety of diseases, including rare genetic disorders. These cell lines represent an important resource for disease modeling with the induced pluripotent stem cell (iPSC) technology. Here we report the generation of iPSCs from EBV-immortalized B-cell lines derived from multiple inherited disease patients via a nonviral method. The reprogramming method for the EBV cell lines involves a distinct protocol compared with that of patient fibroblasts. The B-cell line–derived iPSCs expressed pluripotency markers, retained the inherited mutation and the parental V(D)J rearrangement profile, and differentiated into all 3 germ layer cell types. There was no integration of the reprogramming-related transgenes or the EBV-associated genes in these iPSCs. The ability to reprogram the widely banked patient B-cell lines will offer an unprecedented opportunity to generate human disease models and provide novel drug therapies.
Antifibrotic activities of pirfenidone in animal models
Authors: Schaefer C.J. , Ruhrmund D.W. , Pan L. , Seiwert S.D. , Kossen K.
Published: June 2011

Pirfenidone is an orally active small molecule that has recently been evaluated in large clinical trials for the treatment of idiopathic pulmonary fibrosis, a fatal disease in which the uncontrolled deposition of extracellular matrix leads to progressive loss of lung function. This review describes the activity of pirfenidone in several well-characterised animal models of fibrosis in the lung, liver, heart and kidney. In these studies, treatment-related reductions in fibrosis are associated with modulation of cytokines and growth factors, with the most commonly reported effect being reduction of transforming growth factor-β. The consistent antifibrotic activity of pirfenidone in a broad array of animal models provides a strong preclinical rationale for the clinical characterisation of pirfenidone in pulmonary fibrosis and, potentially, other conditions with a significant fibrotic component.
Towards a better diagnosis of idiopathic pulmonary fibrosis
Authors: Valeyre D.
Published: June 2011

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias, and poses significant clinical challenges. IPF diagnosis is based on clear-cut computed tomography (CT) and histopathological criteria, in an appropriate clinical context. The diagnostic criteria include: 1) exclusion of known causes of interstitial lung disease (including connective tissue disease); 2) usual interstitial pneumonia pattern on high-resolution CT in patients not subjected to surgical lung biopsy; and 3) specific combinations of high-resolution CT with pathological patterns in case of surgical lung biopsy. Improved diagnosis of IPF may help physicians to reduce the delay before an accurate diagnosis is made and increase patient awareness and access to adequate information, follow-up and treatment.
Follow-up and nonpharmacological management of the idiopathic pulmonary fibrosis patient
Authors: Egan J.J.
Published: June 2011

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal form of diffuse interstitial lung disease. Management of IPF requires an orderly approach, with regular evaluations and implementation of both pharmacological and nonpharmacological treatments. Pulmonary rehabilitation can relieve patients from the distressing symptoms of IPF and improve quality of life. Oxygen therapy is central to treatment of all patients. Lung transplantation enhances survival in selected patients. Mechanical ventilation may be used in patients with acute exacerbations, but the prognosis is poor in these cases. Palliative care focuses on symptom management, advance directives and end-of-life planning. Patient support groups may also play an important role.
MiR-204 regulates cardiomyocyte autophagy induced by ischemia-reperfusion through LC3-II
Authors: Xiao Jian , Zhu Xiaoyan , He Bin , Zhang Yufeng , Kang Bo , Wang Zhinong , Ni Xin
Published: June 2011

Background

Autophagy plays a significant role in myocardial ischemia-reperfusion (IR) injury. So it is important to inhibit autophagy to protect cardiomyocytes besides anti-apoptosis. MiRNA has been demonstrated to protect cardiomyocytes against apoptosis during IR, while whether it has anti-autophagy effect has not been known. The aim of this study was to investigate whether miR-204 regulated autophagy by regulating LC3-II protein, which is the marker of autophagosome during myocardial IR injury.

Methods

Adult SD rats were randomized to Control and IR groups. IR group was treated with 30 min ischemia by ligating the left anterior descending coronary artery, followed by 2 h reperfusion by loosing the ligation. The expression of miR-204 was measured by RT-PCR, and LC3 protein was measured by western-blot.

Results

We found that IR induced cardiomyocytes autophagy, together with down-regulation of miR-204 and up-regulation of LC3-II protein. And, we have found that LC3-II protein was regulated by miR-204, using the method of transferring miR-204 mimic or AMO-204 into the cardiomyocytes, before.

Conclusions

These studies provided evidence that miR-204 played an important role in regulating autophagy through LC3-IIprotein during IR.