bluuebunny/crossref_metadata_2025_split huggingface dataset:
Senescence and age‐specific trade‐offs between reproduction and survival in female Asian elephants
Authors: Robinson Matthew R. , Mar Khyne U , Lummaa Virpi 
Published: January 2012

AbstractAlthough studies on laboratory species and natural populations of vertebrates have shown reproduction to impair later performance, little is known of the age‐specific associations between reproduction and survival, and how such findings apply to the ageing of large, long‐lived species. Herein we develop a framework to examine population‐level patterns of reproduction and survival across lifespan in long‐lived organisms, and decompose those changes into individual‐level effects, and the effects of age‐specific trade‐offs between fitness components. We apply this to an extensive longitudinal dataset on female semi‐captive Asian timber elephants (Elephas maximus) and report the first evidence of age‐specific fitness declines that are driven by age‐specific associations between fitness components in a long‐lived mammal. Associations between reproduction and survival are positive in early life, but negative in later life with up to 71% of later‐life survival declines associated with investing in the production of offspring within this population of this critically endangered species.
Implications of sentinel lymph node mapping on nodal staging and prognosis in colorectal cancer
Authors: van der Zaag E. S. , Bouma W. H. , Peters H. M. , Bemelman W. A. , Buskens C. J. 
Published: January 2012

AbstractAim  Sentinel lymph node (SN) mapping for staging in colorectal cancer remains controversial and needs to be validated before it can be implemented in daily practice. We prospectively assessed the effect of SN mapping on nodal staging and its implication on survival in patients with colorectal cancer.Method  Between November 2005 and July 2009, 331 patients underwent a resection for colorectal cancer. In 189 patients (group A) an ex‐vivo SN procedure was performed with immunohistochemical analysis of the SN. Tumour cell deposits between 0.2 mm and 2.0 mm were referred to as micrometastases (pN1mi+). The remaining patients (n = 142, group B) had standard nodal staging. Multivariate Cox regression analysis was performed to identify prognostic factors for disease recurrence.Results  The average number of harvested lymph nodes was higher in group A than in group B (15.5 ± 7.3 vs 12.1 ± 5.2, P < 0.0001). After conventional staging, 81 (43%) patients of group A were judged to have nodal metastasis. This increased to 89 (47%) patients when immunohistochemically detected micrometastases were included. In group B, 50 (35%) patients had nodal metastasis. During follow up, a lower recurrence rate was seen in N0 patients after SN mapping compared with the conventional staging group (4%vs 15.2%, P = 0.04). The SN procedure (hazard ratio = 4.1) was an independent predictor of disease recurrence.Conclusion  The SN procedure results in a more accurate staging of patients with colorectal cancer. This is reflected by a better prognosis of N0 patients after SN mapping.
Correlation of circulating dehydroepiandrosterone with activated protein C generation and carotid intima‐media thickness in male patients with Type 2 diabetes
Authors: Suzuki T. , Yano Y. , Sakamoto M. , Uemura M. , Yasuma T. , Onishi Y. , Sasaki R. , Matsumoto K. , Hayashi T. , Maruyama‐Furuta N. , Akatsuka H. , Gabazza E. C. , Sumida Y. , Takei Y. 
Published: January 2012

Diabet. Med. 29, e41–e46 (2012)AbstractAims  Dehydroepiandrosterone exerts a protective effect against cardiovascular diseases. However, the relationship of dehydroepiandrosterone with the anticoagulant factor activated protein C, generated by the thrombin–thrombomodulin complex on vascular endothelial cells, remains unknown. This study aimed at studying the relationship between dehydroepiandrosterone and activated protein C generation in patients with Type 2 diabetes.Methods  Sixty‐two male patients with Type 2 diabetes were enrolled in this study. Data obtained from 40 healthy male subjects were used as controls. The plasma levels of dehydroepiandrosterone, the activated protein C–protein C inhibitor complex, high‐sensitivity C‐reactive protein and monocyte chemoattractant protein‐1 were measured by enzyme immunoassays. Carotid intima‐media thickness was measured by ultrasonography.Results  The plasma levels of dehydroepiandrosterone (5.15 ± 2.81 vs. 3.76 ± 2.16 ng/ml; P < 0.005) and the activated protein C–protein C inhibitor complex (1.90 ± 1.07 vs. 1.02 ± 0.51 ng/ml; P < 0.001) were significantly lower in patients with diabetes than in normal subjects. Univariate analysis showed a significant correlation of the plasma level of dehydroepiandrosterone with that of the activated protein C–protein C inhibitor complex (r = 0.48, P < 0.001), high‐sensitivity C‐reactive protein (r = −0.30, P < 0.05) and with the mean intima‐media thickness (r = −0.28, P < 0.05) in patients with diabetes. Stepwise multiple regression analysis showed that the plasma level of dehydroepiandrosterone is significantly correlated with the plasma levels of the activated protein C–protein C inhibitor complex (F = 18.06) and high‐sensitivity C‐reactive protein (F = 4.94). There was no correlation between the plasma levels of dehydroepiandrosterone and monocyte chemoattractant protein‐1.Conclusions  These results suggest that lower circulating levels of dehydroepiandrosterone are associated with decreased activated protein C generation and higher intima‐media thickness in patients with Type 2 diabetes.
Targeted treatment of invasive fungal infections accelerates healing of foot wounds in patients with Type 2 diabetes
Authors: Chellan G. , Neethu K , Varma A. K. , Mangalanandan T. S. , Shashikala S. , Dinesh K. R. , Sundaram K. R. , Varma N. , Jayakumar R. V. , Bal A. , Kumar H. 
Published: January 2012

Diabet. Med. 29, e255‐e262 (2012)AbstractAim  To test the hypothesis that fluconazole plus standard care is superior to the standard care for diabetic foot wounds infected with deep‐seated fungal infections.Methods  We carried out a randomized, controlled, open‐label, parallel‐arm study in 75 patients with both fungal and bacterial infections in deep tissues of diabetic foot wounds. Thirty‐seven patients (control group) were given standard care (surgical debridement + culture‐specific antibiotics + offloading + glycaemic control) and 38 patients (treatment group) were given fluconazole 150 mg daily plus standard care. Wound surface area was measured every 2 weeks until the endpoints (complete epithelialization or skin grafting) were met.Results  By week 4, the mean wound surface area reduced to 27.3 from 111.5 cm2 in the treatment group, as opposed to 67.1 from 87.3 cm2 in the control group. Subsequently, the mean wound surface areas were remarkably smaller in the treatment group compared with the control group, and statistically significant differences (P ≤ 0.05) in mean wound surface area were observed between the treatment group and the control group at week 6. However, no statistically significant (P ≤ 0.47) difference in complete healing was observed between the treatment group and the control group, 20 vs. 24. The mean wound healing time for the treatment group was 7.3 weeks, whereas for the control group it was 11.3 weeks (P ≤ 0.022). Similarly, the probability of wound healing in the treatment group was 50 vs. 20% in the control group at week 10.Conclusions  Fluconazole plus standard care was superior to standard care alone in accelerating wound reduction among patients with diabetes with deep‐seated fungal infections in diabetic foot wounds. Those in the treatment group who did heal, healed more quickly (P ≤ 0.022), but overall healing was not different.
Regional differences in the prevalence of known Type 2 diabetes mellitus in 45–74 years old individuals: Results from six population‐based studies in Germany (DIAB‐CORE Consortium)
Authors: Schipf S. , Werner A. , Tamayo T. , Holle R. , Schunk M. , Maier W. , Meisinger C. , Thorand B. , Berger K. , Mueller G. , Moebus S. , Bokhof B. , Kluttig A. , Greiser K. H. , Neuhauser H. , Ellert U. , Icks A. , Rathmann W. , Völzke H. 
Published: January 2012

Diabet. Med. 29, e88–e95 (2012)AbstractAim  In Germany, regional data on the prevalence of Type 2 diabetes mellitus are lacking for health‐care planning and detection of risk factors associated with this disease. We analysed regional variations in the prevalence of Type 2 diabetes and treatment with antidiabetic agents.Methods  Data of subjects aged 45–74 years from five regional population‐based studies and one nationwide study conducted between 1997 and 2006 were analysed. Information on self‐reported diabetes, treatment, and diagnosis of diabetes were compared. Type 2 diabetes prevalence estimates (95% confidence interval) from regional studies were directly standardized to the German population (31 December 2007).Results  Of the 11 688 participants of the regional studies, 1008 had known Type 2 diabetes, corresponding to a prevalence of 8.6% (8.1–9.1%). For the nationwide study, a prevalence of 8.2% (7.3–9.2%) was estimated. Prevalence was higher in men (9.7%; 8.9–10.4%) than in women (7.6%; 6.9–8.3%). The regional standardized prevalence was highest in the east with 12.0% (10.3–13.7%) and lowest in the south with 5.8% (4.9–6.7%). Among persons with Type 2 diabetes, treatment with oral antidiabetic agents was more frequently reported in the south (56.9%) and less in the northeast (46.0%), whereas treatment with insulin alone was more frequently reported in the northeast (21.6%) than in the south (16.4%).Conclusion  The prevalence of known Type 2 diabetes showed a southwest‐to‐northeast gradient within Germany, which is in accord with regional differences in the distribution of risk factors for Type 2 diabetes. Furthermore, the treatment with antidiabetic agents showed regional differences.
Innovation for Inclusive Growth: Towards a Theoretical Framework and a Research Agenda
Authors: George Gerard , McGahan Anita M. , Prabhu Jaideep 
Published: January 2012

abstractInclusive innovation, which we define as innovation that benefits the disenfranchised, is a process as well as a performance outcome. Consideration of inclusive innovation points to inequalities that may arise in the development and commercialization of innovations, and also acknowledges the inequalities that may occur as a result of value creation and capture. We outline opportunities for the development of theory and empirical research around this construct in the fields of entrepreneurship, strategy, and marketing. We aim for a synthesis in views of inclusive innovation and call for future research that deals directly with value creation and the distributional consequences of innovation.
The Rural Creative Class: Counterurbanisation and Entrepreneurship in the Danish Countryside
Authors: Herslund Lise 
Published: January 2012

AbstractThe paper discusses why well educated urban dwellers choose to move to rural areas and start micro businesses, the problems they face, how they try to solve these problems and the implications for rural development. With a dwelling far from the city, the well‐educated in‐migrants start businesses which seek to combine a less stressful everyday life with a continued career. In the start‐up phase, the majority of businesses is in the knowledge sectors, within media and business services, and is oriented towards the metropolitan market. Few businesses seek to private services for the local market. After some years in the countryside, however, the businesses evolve into ‘regional lifestyle businesses’. They remain within the urban sector but have now adapted themselves to the regional market in order to minimise time spent on meeting customers in the city. These rural entrepreneurs combine a small number of well‐established customers in the city with a broader array of services directed toward the regional market. Although their impact on the local rural area is minimal, they operate over a larger regional area, extending networks and providing ‘organisational energy’.
Clinical and radiological differences in posterior reversible encephalopathy syndrome between patients with preeclampsia‐eclampsia and other predisposing diseases
Authors: Liman T. G. , Bohner G. , Heuschmann P. U. , Scheel M. , Endres M. , Siebert E. 
Published: January 2012

Background:  Posterior reversible encephalopathy syndrome (PRES) is a serious maternal complication in pregnancy, but data on the clinicoradiological differences to other etiologies of PRES are scarce. In this study, we aimed to investigate the clinical and imaging characteristics of PRES in preeclampsia‐eclampsia patients compared with other predisposing diseases in a large cohort.Methods:  We retrospectively reviewed the radiological report data bases between January 1999 and August 2010 for patients with PRES. Patients fulfilling the criteria for PRES after detailed investigation of clinical charts and imaging studies were separated into patients with eclampsia‐preeclampsia and other predisposing causes. Various imaging features at onset of symptoms and on follow‐up as well as clinical and paraclinical data were analyzed.Results:  A total of 24 patients with preeclampsia‐eclampsia associated PRES and 72 patients with PRES of other predisposing causes were included into the study. In preeclampsia‐eclampsia patients, headaches were significantly more frequent as initial PRES‐related symptom (P < 0.001), whereas altered mental state was significantly less frequent (P = 0.001). Thalamus, midbrain, and pons affection was significantly less frequent in preeclampsia‐eclampsia associated PRES (P = 0.01). Preeclampsia‐eclampsia patients had significantly less severe edema, less cytotoxic edema, hemorrhage and contrast enhancement, while more frequent complete resolution of edema and less frequent residual structural lesions were seen on follow‐up imaging.Conclusion:  In our PRES cohort, we found major clinicoradiological differences between preeclampsia‐eclampsia and other predisposing causes pointing toward a less severe course of disease in preeclampsia‐eclampsia.
Saturated long‐chain fatty acids activate inflammatory signaling in astrocytes
Authors: Gupta Sunita , Knight Alecia G. , Gupta Shruti , Keller Jeffrey N. , Bruce‐Keller Annadora J. 
Published: January 2012

J. Neurochem. (2012) 120, 1060–1071.AbstractThis study describes the effects of long‐chain fatty acids on inflammatory signaling in cultured astrocytes. Data show that the saturated fatty acid palmitic acid, as well as lauric acid and stearic acid, trigger the release of TNFα and IL‐6 from astrocytes. Unsaturated fatty acids were unable to induce cytokine release from cultured astrocytes. Furthermore, the effects of palmitic acid on cytokine release require Toll‐like receptor 4 rather than CD36 or Toll‐like receptor 2, and do not depend on palmitic acid metabolism to palmitoyl‐CoA. Inhibitor studies revealed that pharmacologic inhibition of p38 or p42/44 MAPK pathways prevents the pro‐inflammatory effects of palmitic acid, whereas JNK and PI3K inhibition does not affect cytokine release. Depletion of microglia from primary astrocyte cultures using the lysosomotropic agent l‐leucine methyl ester revealed that the ability of palmitic acid to trigger cytokine release is not dependent on the presence of microglia. Finally, data show that the essential ω‐3 fatty acid docosahexaenoic acid acts in a dose‐dependent manner to prevent the actions of palmitic acid on inflammatory signaling in astrocytes. Collectively, these data demonstrate the ability of saturated fatty acids to induce astrocyte inflammation in vitro. These data thus raise the possibility that high levels of circulating saturated fatty acids could cause reactive gliosis and brain inflammation in vivo, and could potentially participate in the reported adverse neurologic consequences of obesity and metabolic syndrome.
Linkage of cardiac gene expression profiles and ETS2 with lifespan variability in rats
Authors: Sheydina Anna , Volkova Maria , Jiang Liqun , Juhasz Ondrej , Zhang Jing , Tae Hyun‐Jin , Perino Maria G. , Wang Mingyi , Zhu Yi , Lakatta Edward G. , Boheler Kenneth R. 
Published: January 2012

SummaryLongevity variability is a common feature of aging in mammals, but the mechanisms responsible for this remain largely unknown. Using microarray datasets coupled with prediction analysis of microarrays (PAM), we identified a set of 252 cardiac transcripts predictive of relative lifespan in Wistar and Fisher 344 rats. Prediction analysis of microarrays ‘tests’ of rat heart transcriptomes from a third longer lived Fisher × Norway Brown rat strain validated the predictive value of this gene subset. The expression patterns of these genes were highly conserved, and corresponding promoter regions were employed to identify common cis–elements and trans‐activating factors implicated in their control. Specifically, four transcription factors (Max, Ets2, Erg, and Msx2) present in heart displayed longevity‐dependent, strain‐independent changes in abundance, but only ETS2 had an expression profile that directly correlated with the relative lifespan gene set. In heart, ETS2 was prevalent in cardiomyocytes (CMs) and showed a high degree of myocyte‐to‐myocyte variability predominantly in adult rat hearts prior to the exponential increase in the rate of mortality. Exclusively in this group, elevated ETS2 significantly overlapped with TUNEL staining in heart myocytes. In response to sympathetic stimuli, ETS2 is also up‐regulated, and functionally, adenovirus‐mediated over‐expression of ETS2 promotes apoptosis‐inducing factor‐mediated, caspase‐independent programmed necrosis exclusively in CMs that can be fully inhibited by the PARP‐1 inhibitor DPQ. We conclude that variations in ETS2 abundance in hearts of adult rodents and the associated loss of CMs contribute at least partially, to the longevity variability observed during normal aging of rats through activation of programmed necrosis.
Motivations and barriers in using distributed supply chain simulation
Authors: Mustafee Navonil , Taylor Simon , Katsaliaki Korina , Dwivedi Yogesh , Williams Michael 
Published: January 2012

AbstractDiscrete event simulation (DES) is a technique that is used by analysts to take informed decisions regarding an existing or proposed system of interest.DESmodels typically represent the processes associated with various business units. However, in the case of supply chains more than one business unit may need to be modelled as different organisations may be responsible for various supply chain operations such as manufacturing, transport and logistics, distribution, warehouse operations, etc. Organisations can be protective about their internal processes and can have concerns regarding data/information security and privacy. Thus it could be argued that creating a singleDESsupply chain model representing the various inter‐organisational processes is usually not an option since this will run counter to organisational privacy. Further, issues such as data transfer, model composability and execution speed may also make a single model approach problematic. A potential solution could be to create several distinct and well‐definedDESmodels, each modelling the processes associated with one specific supply chain business unit, linked together over the internet. We refer to this possible distributed approach as Distributed Supply Chain Simulation (DSCS). Although this approach holds great promise, there are technical barriers in usingDSCS. The paper discusses the benefits and barriers of a distributed approach and then, using a healthcareDSCS, the technological feasibility is demonstrated. In conclusion, the paper argues that adopting a standardised approach toDSCSwill remove a major barrier to its use.
Epithelial Na+ channel activity in human airway epithelial cells: the role of serum and glucocorticoid‐inducible kinase 1
Authors: Watt Gordon B , Ismail Noor AS , Caballero Agustin Garcia , Land Stephen C , Wilson Stuart M 
Published: January 2012

BACKGROUND AND PURPOSE Glucocorticoids appear to control Na+ absorption in pulmonary epithelial cells via a mechanism dependent upon serum and glucocorticoid‐inducible kinase 1 (SGK1), a kinase that allows control over the surface abundance of epithelial Na+ channel subunits (α‐, β‐ and γ‐ENaC). However, not all data support this model and the present study re‐evaluates this hypothesis in order to clarify the mechanism that allows glucocorticoids to control ENaC activity.EXPERIMENTAL APPROACH Electrophysiological studies explored the effects of agents that suppress SGK1 activity upon glucocorticoid‐induced ENaC activity in H441 human airway epithelial cells, whilst analyses of extracted proteins explored the associated changes to the activities of endogenous protein kinase substrates and the overall/surface expression of ENaC subunits.KEY RESULTS Although dexamethasone‐induced (24 h) ENaC activity was dependent upon SGK1, prolonged exposure to this glucocorticoid did not cause sustained activation of this kinase and neither did it induce a coordinated increase in the surface abundance of α‐, β‐ and γ‐ENaC. Brief (3 h) exposure to dexamethasone, on the other hand, did not evoke Na+ current but did activate SGK1 and cause SGK1‐dependent increases in the surface abundance of α‐, β‐ and γ‐ENaC.CONCLUSIONS AND IMPLICATIONS Although glucocorticoids activated SGK1 and increased the surface abundance of α‐, β‐ and γ‐ENaC, these responses were transient and could not account for the sustained activation of ENaC. The maintenance of ENaC activity did, however, depend upon SGK1 and this protein kinase must therefore play an important but permissive role in glucocorticoid‐induced ENaC activation.
Risky Decision‐Making: An fMRI Study of Youth at High Risk for Alcoholism
Authors: Cservenka Anita , Nagel Bonnie J. 
Published: January 2012

Background:  Adolescents with a family history of alcoholism (FHP) are at risk for developing an alcohol use disorder (AUD), and some studies indicate that FHP individuals show deficits in executive functioning. The ability to make adaptive decisions is one aspect of successful executive functioning that is often measured during risk‐taking tasks; however, this behavior has not been examined in FHP youth. As impaired decision‐making could predispose FHP youth to make poor choices related to alcohol use, the current study examined the neural substrates of risk‐taking in FHP adolescents and their family history negative (FHN) peers.Methods:  Thirty‐one (18 FHP, 13 FHN) youth between 13 and 15 years old were included in this study. All youth had used little to no alcohol prior to study involvement. Functional magnetic resonance imaging was used to examine the neural substrates of risk‐taking during the Wheel of Fortune (WOF) decision‐making task (Ernst et al., 2004) in FHP and FHN youth.Results:  FHP youth did not differ from FHN youth in risk‐taking behavior, but showed less brain response during risky decision‐making in right dorsolateral prefrontal cortex and right cerebellar regions compared with FHN peers.Conclusions:  Despite no behavioral differences on the WOF decision‐making task, FHP youth exhibited atypical neural response during risk‐taking compared with FHN peers. Atypical brain activity, in regions implicated in executive functioning could lead to reduced cognitive control, which may result in risky choices regarding alcohol use. This could help explain the higher rates of AUDs seen in FHP adolescents. Further examination of risky behavior and associated brain response over the course of adolescence is necessary to characterize the vulnerabilities of FHP youth in the absence of alcohol abuse.