bluuebunny/crossref_metadata_2025 huggingface dataset:
Incremental Learning and Memory Consolidation of Whole Body Human Motion Primitives
Authors: Kulić Dana , Nakamura Yoshihiko
Published: August 2009

The ability to learn during continuous and on-line observation would be advantageous for humanoid robots, as it would enable them to learn during co-location and interaction in the human environment. However, when motions are being learned and clustered on-line, there is a trade-off between classification accuracy and the number of training examples, resulting in potential misclassifications both at the motion and hierarchy formation level. This article presents an approach enabling fast on-line incremental learning, combined with an incremental memory consolidation process correcting initial misclassifications and errors in organization, to improve the stability and accuracy of the learned motions, analogous to the memory consolidation process following motor learning observed in humans. Following initial organization, motions are randomly selected for reclassification, at both low and high levels of the hierarchy. If a better reclassification is found, the knowledge structure is reorganized to comply. The approach is validated during incremental acquisition of a motion database containing a variety of full body motions.1
A Computational Model of Social-Learning Mechanisms
Authors: Lopes Manuel , Melo Francisco S. , Kenward Ben , Santos-Victor José
Published: August 2009

In this article we propose a computational model that describes how observed behavior can influence an observer’s own behavior, including the acquisition of new task descriptions. The sources of influence on our model’s behavior are: beliefs about the world’s possible states and actions causing transitions between them; baseline preferences for certain actions; a variable tendency to infer and share goals in observed behavior; and a variable tendency to act efficiently to reach rewarding states. Acting on these premises, our model is able to replicate key empirical studies of social learning in children and chimpanzees. We demonstrate how a simple artificial system can account for a variety of biological social transfer phenomena, such as goal-inference and over-imitation, by taking into account action constraints and incomplete knowledge about the world dynamics.
Oral Antithrombotic Inhibitors: Dabigatran Etexilate, Meeting an Unmet Need?
Authors: Hull Russell
Published: August 2009

Although effective, vitamin K antagonists (VKAs) are challenging to use because of their slow onset and offset of action, narrow therapeutic window, multiple dietary and drug interactions, and unpredictable anticoagulant effect. Accordingly, it is recognized that there is an unmet need for an oral thrombotic inhibitor that does not require monitoring and has a rapid onset of action. There is also an unmet need in the field of thromboprophylaxis against venous thromboembolism (VTE) in high-risk patients. The topic of this Supplement is the evidence for the use of dabigatran in high-risk orthopedic patients, namely patients with hip and knee athroplasty. An oral therapy with an immediate reliable and predictable anticoagulant effect without the need for coagulation monitoring and without any long-term hepatic or safety concerns will be a major advance in the management of patients with various thrombotic disorders.
Taking Control of Sex?
Authors: Garlick Steve
Published: August 2009

It is widely acknowledged that gender is a key category in pornography, yet the relation of the latter to contemporary masculinities remains relatively obscure. Although there is a substantial critical literature on the positioning and treatment of women in pornography, the connection between the consumption of pornographic images and the social construction of hegemonic masculinity has been more often presumed than examined. This lacuna becomes more apparent when juxtaposed with the profusion and proliferation of Internet porn in recent years. Rather than enter into existing antiporn or proporn debates, this article seeks to pose a different set of questions about the relationship between masculinity, technology, and pornography. It suggests that the Internet produces a qualitative change in the way in which viewers are affected by pornography and that this has implications for contemporary gender relations. Beyond men’s control over women’s bodies, Internet porn participates in the larger drama of a technological confrontation between men and nature—one in which control and the meaning of masculinity is perpetually at stake.
‘Empty Nets’
Authors: Allen Christopher S.
Published: August 2009

The Social Democratic parties of Germany and Sweden were part of ‘third way’ movements common to such political parties during the mid-1990s. By continuing to moderate their positions and move away from their traditional bases towards the centre, they seemed to embody — a generation later — a second embracing of Kirchheimer’s ‘catch-all’ party thesis. But unlike its 1960s’ incarnation, each of them in the mid-1990s disregarded their left flanks and saw considerable growth of both Green and Left (former communist) parties fill the policy space that social democracy had relinquished. Both parties no longer lead their governments. This article suggests that the decline of social democracy in Germany and Sweden can be understood by a nuanced interpretation of the Kirchheimer thesis. Ultimately, it is argued that the failure of both parties to maintain electoral dominance results, paradoxically, from their overemphasis on the political centre, which left a lucrative space for left-wing parties to occupy especially in a PR setting. Kirchheimer helps us understand this pattern, because the focus on the centre leaves an ideologically moribund electorate that created space for Left parties to institutionally renew or adapt themselves to address the needs of these forgotten voters. This central hypothesis, along with others that derive from the catch-all thesis, is tested empirically with historical analysis and electoral and opinion data.
Holding Their Own
Authors: Spoon Jae-Jae
Published: August 2009

In his seminal work, Kirchheimer (1966) argued that as larger parties transformed into catch-all parties we would see the disappearance of small parties. We know, however, that Green parties are one example of small parties that have persisted in many European party systems. In this article, I seek to explain this inconsistency. I argue that Kirchheimer did not anticipate the development and growth of the New Politics agenda or of Green parties. These parties, moreover, have endured because of their desire to gain electoral representation and maintain their distinct policy positions. To test this argument, I examine the electoral strategies and policy preferences of the British and French Green parties over the past decade. The results confirm my hypotheses. The findings not only update Kirchheimer’s theory, but also have important implications for our understanding of Green party behaviour and potential for longevity more generally.
Choosing screening instrument and cut-point on screening instruments. A comparison of methods
Authors: Søgaard Hans J.
Published: August 2009

Aims: This study analyzes decisive measures of efficiency of a test, receiver operating characteristic (ROC) analysis and QROC analysis combined with considerations about clinical, health-economic, and ethical aspects when choosing screening instruments. Methods: Analyses of Common Mental Disorders Screening Questionnaire (CMD-SQ) and its subscales SCL-SOM, Whiteley-7, SCL-ANX4, SCL-DEP6, SCL-8, plus combinations, for early detection of psychiatric disorders, are the subject for this analysis. In all, 46.4% of 2,414 new people with continuous sickness absence for more than eight weeks over one year in a well-defined Danish population of 120,000 inhabitants participated in the study. The study was performed as a two phase study. All 1,121 persons in Phase 1 filled in the CMD-SQ. In Phase 2, a random subsample of Phase 1 on 337, the people were further examined by a psychiatrist using SCAN as gold standard. The analyses were performed as weighted analyses on Phase 2. Results: From 17 analyses it was shown that the efficiency of a test, ROC analyses, and QROC analyses resulted in different optimal scales and cut-points. The random possibility of a positive test or negative test in the population is discussed for efficiency and ROC analyses. QROC analyses correct for this by the relative κ-values as decisive measures. However, QROC analyses may discard tests of value, all depending on the purpose of the test. Conclusions: In supplement to test statistics the capacity of services to follow up on screening, ethics, and health economy are issues that should be considered in deciding what rating scale and cut-point should be adopted.
Sports camp with six months of support from a local sports club as a treatment for childhood obesity
Authors: Nowicka Paulina , Lanke Jan , Pietrobelli Angelo , Apitzsch Erwin , Flodmark Carl-Erik
Published: August 2009

Aims: Although childhood obesity is becoming increasingly prevalent, treatment options are limited and the continued development of effective treatment strategies is necessary. It is equally important to explore involvement of other resources in society, such as sports associations. This study was designed to investigate the possibility of reducing the degree of obesity in obese children by focusing on physical activity as an intervention. Methods: Seventy-six children (40 boys) aged 8—12 years (mean age 10.5 years, mean body mass index (BMI) 28.9, standard deviation (SD) 3.0; mean BMI z-score 3.24, SD 0.49) were invited to participate in a one-week sports camp and six-month support system. After the camp a sports coach from a local sports club supported the child during participation in a chosen sport for six months. Weight, height, body composition (using dual energy x-ray absorptiometry and magnetic resonance imaging), and lifestyle (using a questionnaire) were measured at baseline and after 12 months. Data were pooled from two camps, one with a self-selected control group and one randomized controlled trial. Results: Twelve months after the camp the intervention group had a significant decrease in BMI z-score (baseline BMI z-score 3.22; follow up 3.10, p = 0.023). The control group also reduced their BMI z-score (baseline BMI z-score 3.27; follow up 3.18, p = 0.022). No differences were found in baseline values, follow-up values, or changes in BMI z-score between groups, nor between boys and girls. Conclusions: The focus on physical activity as an intervention had no effect on degree of obesity when compared with a waiting list control group.
Psychometric analysis of Common Mental Disorders — Screening Questionnaire (CMD-SQ) in long-term sickness absence
Authors: Søgaard Hans Jørgen , Bech Per
Published: August 2009

Aims: Mental disorders often go undetected in primary care, for persons awarded disability pension, and in sick-leave certificates. No validity tests of instruments for detection and measurement of mental disorders have been performed in long-term sickness absence (LSA). This is the aim of the present study for Common Mental Disorders — Screening Questionnaire (CMD-SQ). Methods: It is validity tested in a well-defined Danish population comprising all persons on continuous sickness absence just exceeding eight weeks. CMD-SQ is composed of SCL-SOM (somatization), Whiteley-7 (illness worry and conviction), SCL-ANX4 (anxiety), SCL-DEP6 (depression), SCL-8 (emotional disorder), and CAGE (alcohol dependency). Results: Of 2,414 incident persons on long-term sickness absence within one year, 1,121 participated in the study by filling in CMD-SQ and a subsample of 337 was diagnosed by a psychiatric examination including Present State Examination. Psychometric properties such as scalability and monotonicity, construct validity, and predictive validity were analyzed. Further change over time was analyzed. SCL-SOM and Whiteley-7 showed slight psychometric and screening statistics whereas a combined scale of SC-ANX4, SCL-DEP6, and SCL-8, called SCL-8AD, showed the best and excellent psychometric and screening statistics. Conclusions: SCL-8AD, a sub-scale of CMD-SQ, is a promising candidate for screening and measurement of mental disorders in long-term sickness absence.
Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity
Authors: Høi-Hansen Thomas , Pedersen-Bjergaard Ulrik , Andersen Rikke Due , Kristensen Peter Lommer , Thomsen Carsten , Kjær Troels , Høgenhaven Hans , Smed Annelise , Holst Jens Juul , Dela Flemming , Boomsma Frans , Thorsteinsson Birger
Published: August 2009

Introduction. High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patients with low RAS activity. Materials and methods. Nine patients with type 1 diabetes and high and nine with low RAS activity were subjected to hypoglycaemia and euglycaemia in a cross-over study using an intravenous insulin infusion protocol. Cognitive function, electroencephalography, auditory evoked potentials and hypoglycaemic symptoms were recorded.

Results. At a hypoglycaemic nadir of 2.2 (SD 0.3) mmol/L the high RAS group displayed significant deterioration in cognitive performance during hypoglycaemia in the three most complex reaction time tasks. In the low RAS group, hypoglycaemia led to cognitive dysfunction in only one reaction time task. The high RAS group reported lower symptom scores during hypoglycaemia than the low RAS group, suggesting poorer hypoglycaemia awareness. Conclusion. High RAS activity is associated with increased cognitive dysfunction and blunted symptoms during mild hypoglycaemia compared to low RAS activity. This may explain why high RAS activity is a risk factor for severe hypoglycaemia in type 1 diabetes.
Association of angiotensin-converting enzyme intron 16 insertion/deletion polymorphism with history of foetal loss
Authors: Bukreeva Larisa , Grigorov Alexander , Kiesewetter Holger , Hoppe Berthold
Published: August 2009

Introduction. The angiotensin-converting enzyme (ACE) intron 16 insertion/deletion (I/D) polymorphism is associated with ACE activity and has been discussed as a risk factor for pre-eclampsia. Disturbances of uteroplacental circulation are involved in the pathogenesis of pre-eclampsia. In this study, we tested whether the ACE I/D genotype is associated with history of foetal loss (FL) or uteroplacental dysfunction (UPD).

Patients and methods. ACE I/D genotype was determined in 312 women presenting with a history of FL and 112 women admitted because of UPD. The association of the ACE I/D genotype with FL or UPD was assessed in a case-control study using 527 patients with diagnoses other than FL or UPD. To exclude potential biases due to associations of this genotype with other diagnoses, we additionally performed a case-control study using 553 healthy controls. Results. ACE I/D genotype was significantly associated with history of FL in both case-control studies (patient controls: odds ratio 1.52, p<0.02; healthy controls: odds ratio 1.48, p=0.02). There was no evidence for allele-dose dependency. No association of the ACE I/D genotype with UPD could be detected.

Conclusions. The ACE I/D genotype exhibits a statistically significant association with a history of FL. These results corroborate an involvement of the renin-angiotensin system in pregnancy complications.
Thermal Resistance Properties of Paratrooper Clothing
Authors: Shekar R. Indu , Kotresh T.M. , Subbulakshmi M.S. , Vijayalakshmi S.N. , Prasad A.S. Krishna
Published: August 2009

Combat free fall paratroopers’ (CFF) protective clothing, comprising of non-woven insulating material, inherently flame retardant Nomex fabric and cotton fabric combinations are studied under simulated conditions of conduction and sweat using Thermolobo-II technique. The results show that Non—woven insulating materials exhibit high thermal resistance in dry contact method under moderate wind velocity, whereas the thermal resistance values measured under wet conditions is significantly lower. The effect of air layer thickness, permeability and other important parameters, such as porosity, surface area have also been considered and correlated to assess the overall performance of protective clothing ensemble.
Clinical Librarian Attendance at General Surgery Quality of Care Rounds (Morbidity and Mortality Conference)
Authors: Greco Elisa , Englesakis Marina , Faulkner Amy , Trojan Boguslawa , Rotstein Lorne E. , Urbach David R.
Published: August 2009

Quality of Care rounds, also known as Mortality and Morbidity conferences, are an important and time-honored forum for quality audit in clinical surgery services. The authors created a modification to their hospital’s Quality of Care rounds by incorporating a clinical librarian, who assisted residents in conducting literature reviews related to clinical topics discussed during the rounds. The objective of this article is to describe the authors’ experience with this intervention. The clinical librarian program has greatly improved the Quality of Care rounds by aiding in literature searches and quality of up-to-date, evidence-based presentations.
Feasibility of a High Intrathoracic Esophagogastric Anastomosis Without Thoracic Access After Laparoscopic-Assisted Transhiatal Esophagectomy: A Pilot Experimental Study
Authors: Bintintan Vasile V. , Mehrabi Arianeb , Fonouni Hamidreza , Esmaeilzadeh Majid , Müller-Stich Beat P. , Funariu Gheorghe , Ciuce Constantin , Gutt Carsten N.
Published: August 2009

Introduction. The aim of the present study was to evaluate the feasibility of a technique that uses solely the transhiatal approach to create a high intrathoracic esophagogastric anastomosis after laparoscopic transhiatal resection of the distal esophagus. Method. Using a laparoscopic approach, the esophagi of 10 midsized pigs were dissected and transected as high as possible in the thorax, and the anvil of a circular stapler was introduced perorally into the esophageal stump. Through a midline short laparotomy, the circular stapler was inserted into the gastric tube and advanced through the hiatus to be connected with the anvil and create the anastomosis. Results. Development of the technique was completed within the first 6 experiments. The last 4 operations were entirely successful, standardized, and easily reproducible. Conclusion. The technique is feasible in this experimental setting. Further studies are required to establish if there is a clinical role for this technique in esophageal surgery.
Help-Seeking Behaviors of Men Sexual Assault Survivors
Authors: Masho Saba W. , Alvanzo Anika
Published: August 2009

Men sexual assault is a serious public health issue that is mostly underreported and unrecognized. Despite serious deleterious effects of sexual assault, most men victims do not seek professional help. This study was conducted to examine predictors of help-seeking practices among 91 men sexual assault survivors from a population-based survey. The study showed only 17.6% of the victims sought professional help. Logistic regression analysis demonstrated that physical injury (OR = 6.58, 95% CI = 1.08-40.19), perpetration by family or friend (OR = 6.42, 95% CI = 1.47-28.04), history of rape before the age of 18 (OR = 0.43, 95% CI = 0.11-1.69), and threat at the time of incident (OR = 7.08, 95% CI = 1.52-33.03) were significant predictors of help-seeking practices. This study confirms that the majority of men sexual assault victims do not seek professional help. Victims with physical injury or threat were more likely to seek help. Further study should investigate barriers for help-seeking practices. Efforts should be made to reach men with a history of sexual assault.
Low Rates of Vasectomy Among Minorities: A Result of Differential Receipt of Counseling?
Authors: Borrero Sonya , Moore Charity G. , Creinin Mitchell D. , Ibrahim Said A.
Published: August 2009

Male sterilization is a highly effective contraceptive method that is underused especially among minorities. This analysis examined the association between race/ethnicity and receipt of sterilization counseling. This study used data collected by the 2002 National Survey of Family Growth. The analysis included men 15 to 44 years old who had not undergone sterilization. The outcome was receipt of sterilization counseling in the 12 months prior to interview, and the primary predictor was race/ethnicity. Sociodemographic characteristics, history of fathering an unintended birth, intention for more children, and access to health care were examined as confounders. Sixty-one (1.7%) men reported receiving sterilization counseling. Although counseling was reported more commonly by Black and Hispanic men compared with White men, the rates were not significantly different (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 0.8-7.1 and OR = 1.9, 95% CI = 0.9-4.1, respectively). In this nationally representative sample of men aged 15 to 44 years, there were exceedingly low rates of sterilization counseling for all men regardless of race/ethnicity.
Natural nanoclays: applications and future trends – a Chilean perspective
Authors: Calabi Floody M. , Theng B. K. G. , Reyes P. , Mora M. L.
Published: August 2009

Because of their large potential for agricultural, industrial and medicinal applications, nanomaterials have been the focus of much research during the past few decades. Nanoclays are natural nanomaterials that occur in the clay fraction of soil, among which montmorillonite and allophane are the most important species. Montmorillonite is a crystalline hydrous phyllosilicate (layer silicate). Organically-modified montmorillonites or ‘organoclays’, formed by intercalation of quaternary ammonium cations, have long been used as rheological modifiers and additives in paints, inks, greases and cosmetics and as carriers and delivery systems for the controlled release of drugs. Perhaps the largest single usage of organoclays over recent years has been in the manufacture of polymer-clay nanocomposites. These organic–inorganic hybrid materials show superior mechanical, thermal and gas-barrier properties. Organoclays are also useful in pollution control and water treatment. Allophane is a non-crystalline aluminosilicate derived from the weathering of volcanic ash. A large proportion of the agricultural land in Chile is covered by volcanic soils,the clay fraction of which is dominated by allophane. Consisting of nanosize (3.5–5.0 nm) hollow spherules, allophane is a suitable support material for enzyme immobilization. Allophane is also effective at adsorbing phenolic compounds and colour from kraft mill effluents and phosphate from water and wastewater.
Comparison of the mineralogical effects of an experimental forest fire on a goethite/ferrihydrite soil with a topsoil that contains hematite, maghemite and goethite
Authors: Nørnberg P. , Vendelboe A. L. , Gunnlaugsson H. P. , Merrison J. P. , Finster K. , Jensen S. K
Published: August 2009

A long-standing unresolved puzzle related to the Danish temperate humid climate is the presence of extended areas with large Fe contents, where goethite and ferrihydrite are present in the topsoil along with hematite and maghemite. Hematite and, particularly, maghemite would normally be interpreted as the result of high temperature as found after forest fires. However, a body of evidence argues against these sites having been exposed to fire. In an attempt to get closer to an explanation of this Fe mineralogy, an experimental forest fire was produced. The results showed a clear mineralogical zonation down to 10 cm depth. This was not observed at the natural sites, which contained a mixture of goethite/ferrihydrite, hematite and maghemite down to 20 cm depth. The experimental forest fire left charcoal and ashes at the topsoil, produced high pH and decreased organic matter content, all of which is in contrast to the natural sites. The conclusion from this work is that the mineralogy of these sites is not consistent with exposure to forest fire, but may instead result from long-term transformation in a reducing environment, possibly involving microbiology.
Enhancement of vascular progenitor potential by protein kinase A through dual induction of Flk-1 and Neuropilin-1
Authors: Yamamizu Kohei , Kawasaki Kyoko , Katayama Shiori , Watabe Tetsuro , Yamashita Jun K.
Published: August 2009

Fine tuning of vascular endothelial growth factor (VEGF) signaling is critical in endothelial cell (EC) differentiation and vascular development. Nevertheless, the system for regulating the sensitivity of VEGF signaling has remained unclear. Previously, we established an embryonic stem cell culture reproducing early vascular development using Flk1 (VEGF receptor-2)+ cells as common progenitors, and demonstrated that cyclic adenosine monophosphate (cAMP) enhanced VEGF-induced EC differentiation. Here we show that protein kinase A (PKA) regulates sensitivity of Flk1+ vascular progenitors to VEGF signaling for efficient EC differentiation. Blockade of PKA perturbed EC differentiation and vascular formation in vitro and ex vivo. Overexpression of constitutive active form of PKA (CA-PKA) potently induced EC differentiation and vascular formation. Expression of Flk1 and Neuropilin-1 (NRP1), which form a selective and sensitive receptor for VEGF165, was increased only in CA-PKA–expressing progenitors, enhancing the sensitivity of the progenitors to VEGF165 by more than 10 times. PKA activation induced the formation of a VEGF165, Flk1, and NRP1 protein complex in vascular progenitors. These data indicate that PKA regulates differentiation potential of vascular progenitors to be endothelial competent via the dual induction of Flk1 and NRP1. This new-mode mechanism regulating “progenitor sensitivity” would provide a novel understanding in vascular development and regeneration.
The role of the human cytomegalovirus UL111A gene in down-regulating CD4+ T-cell recognition of latently infected cells: implications for virus elimination during latency
Authors: Cheung Allen K. L. , Gottlieb David J. , Plachter Bodo , Pepperl-Klindworth Sandra , Avdic Selmir , Cunningham Anthony L. , Abendroth Allison , Slobedman Barry
Published: August 2009

The capacity of human cytomegalovirus (HCMV) to establish and maintain a latent infection from which it can later reactivate ensures its widespread distribution in the population, but the mechanisms enabling maintenance of latency in the face of a robust immune system are poorly understood. We examined the role of the HCMV UL111A gene, which encodes homologs of the immunosuppressive cytokine interleukin-10 in the context of latent infection of myeloid progenitor cells. A UL111A deletion virus was able to establish, maintain, and reactivate from experimental latency in a manner comparable with parental virus, but major histocompatibility complex class II levels increased significantly on the surfaces of cells infected with the deletion virus. Importantly, there was an increase in both allogeneic and autologous peripheral blood mononuclear cells and CD4+ T-cell responses to UL111A deletion virus-infected myeloid progenitors, indicating that loss of the capacity to express viral interleukin-10 during latency results in latently infected cells becoming more readily recognizable by a critical arm of the immune response. The detection of a viral gene that suppresses CD4+ T-cell recognition of latently infected cells identifies an immune evasion strategy that probably enhances the capacity of HCMV to persist in a latent state within the human host.
Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts
Authors: Le Dieu Rifca , Taussig David C. , Ramsay Alan G. , Mitter Richard , Miraki-Moud Faridah , Fatah Rewas , Lee Abigail M. , Lister T. Andrew , Gribben John G.
Published: August 2009

Understanding how the immune system in patients with cancer interacts with malignant cells is critical for the development of successful immunotherapeutic strategies. We studied peripheral blood from newly diagnosed patients with acute myeloid leukemia (AML) to assess the impact of this disease on the patients' T cells. The absolute number of peripheral blood T cells is increased in AML compared with healthy controls. An increase in the absolute number of CD3+56+ cells was also noted. Gene expression profiling on T cells from AML patients compared with healthy donors demonstrated global differences in transcription suggesting aberrant T-cell activation patterns. These gene expression changes differ from those observed in chronic lymphocytic leukemia (CLL), indicating the heterogeneous means by which different tumors evade the host immune response. However, in common with CLL, differentially regulated genes involved in actin cytoskeletal formation were identified, and therefore the ability of T cells from AML patients to form immunologic synapses was assessed. Although AML T cells could form conjugates with autologous blasts, their ability to form immune synapses and recruit phosphotyrosine signaling molecules to the synapse was significantly impaired. These findings identify T-cell dysfunction in AML that may contribute to the failure of a host immune response against leukemic blasts.
Bone marrow stem and progenitor cell contribution to neovasculogenesis is dependent on model system with SDF-1 as a permissive trigger
Authors: Madlambayan Gerard J. , Butler Jason M. , Hosaka Koji , Jorgensen Marda , Fu Dongtao , Guthrie Steven M. , Shenoy Anitha K. , Brank Adam , Russell Kathryn J. , Otero Jaclyn , Siemann Dietmar W. , Scott Edward W. , Cogle Christopher R.
Published: August 2009

Adult bone marrow (BM) contributes to neovascularization in some but not all settings, and reasons for these discordant results have remained unexplored. We conducted novel comparative studies in which multiple neovascularization models were established in single mice to reduce variations in experimental methodology. In different combinations, BM contribution was detected in ischemic retinas and, to a lesser extent, Lewis lung carcinoma cells, whereas B16 melanomas showed little to no BM contribution. Using this spectrum of BM contribution, we demonstrate the necessity for site-specific expression of stromal-derived factor-1α (SDF-1α) and its mobilizing effects on BM. Blocking SDF-1α activity with neutralizing antibodies abrogated BM-derived neovascularization in lung cancer and retinopathy. Furthermore, secondary transplantation of single hematopoietic stem cells (HSCs) showed that HSCs are a long-term source of neovasculogenesis and that CD133+CXCR4+ myeloid progenitor cells directly participate in new blood vessel formation in response to SDF-1α. The varied BM contribution seen in different model systems is suggestive of redundant mechanisms governing postnatal neovasculogenesis and provides an explanation for contradictory results observed in the field.
A randomized, controlled clinical trial of ketoprofen for sickle-cell disease vaso-occlusive crises in adults
Authors: Bartolucci Pablo , El Murr Tony , Roudot-Thoraval Françoise , Habibi Anoosha , Santin Aline , Renaud Bertrand , Noël Violaine , Michel Marc , Bachir Dora , Galactéros Frédéric , Godeau Bertrand
Published: August 2009

Vaso-occlusive crisis (VOC) is the primary cause of hospitalization of patients with sickle-cell disease. Treatment mainly consists of intravenous morphine, which has many dose-related side effects. Nonsteroidal antiinflammatory drugs have been proposed to provide pain relief and decrease the need for opioids. Nevertheless, only a few underpowered trials of nonsteroidal antiinflammatory drugs for sickle-cell VOC have been conducted, and conflicting results were reported. We conducted a phase 3, double-blind, randomized, placebo-controlled trial with ketoprofen (300 mg/day for 5 days), a nonselective cyclooxygenase inhibitor, for severe VOC in adults. A total of 66 VOC episodes were included. The primary efficacy outcome was VOC duration. The secondary end points were morphine consumption, pain relief, and treatment failure. Seven VOC episodes in each group were excluded from the analysis because of treatment failures. No significant between-group differences were observed for the primary outcome or the secondary end points. Thus, although ketoprofen was well-tolerated, it had no significant efficacy as treatment of VOC requiring hospitalization. These findings argue against its systematic use in this setting.
Stage-specific susceptibility of human erythroblasts to Plasmodium falciparum malaria infection
Authors: Tamez Pamela A. , Liu Hui , Fernandez-Pol Sebastian , Haldar Kasturi , Wickrema Amittha
Published: August 2009

Malaria parasites are known to invade and develop in erythrocytes and reticulocytes, but little is known about their infection of nucleated erythroid precursors. We used an in vitro cell system that progressed through basophilic, polychromatic, orthochromatic, and reticulocyte stages to mature erythrocytes. We show that orthochromatic cells are the earliest stages that may be invaded by Plasmodium falciparum, the causative agent of fatal human malaria. Susceptibility to invasion is distinct from intracellular survival and occurs at a time of extensive erythroid remodeling. Together these data suggest that the potential for complexity of host interactions involved in infection may be vastly greater than hitherto realized.
Automated threshold detection for auditory brainstem responses: comparison with visual estimation in a stem cell transplantation study
Authors: Bogaerts Sofie , Clements John D , Sullivan Jeremy M , Oleskevich Sharon
Published: August 2009

Background

Auditory brainstem responses (ABRs) are used to study auditory acuity in animal-based medical research. ABRs are evoked by acoustic stimuli, and consist of an electrical signal resulting from summated activity in the auditory nerve and brainstem nuclei. ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Traditionally, threshold has been assessed by visual estimation of a series of ABRs evoked by different sound intensities. Here we develop an automated threshold detection method that eliminates the variability and subjectivity associated with visual estimation.

Results

The automated method is a robust computational procedure that detects the sound level at which the peak amplitude of the evoked ABR signal first exceeds four times the standard deviation of the baseline noise. Implementation of the procedure was achieved by evoking ABRs in response to click and tone stimuli, under normal and experimental conditions (adult stem cell transplantation into cochlea). Automated detection revealed that the threshold shift from pre- to post-surgery hearing levels was similar in mice receiving stem cell transplantation or sham injection for click and tone stimuli. Visual estimation by independent observers corroborated these results but revealed variability in ABR threshold shifts and significance levels for stem cell-transplanted and sham-injected animals.

Conclusion

In summary, the automated detection method avoids the subjectivity of visual analysis and offers a rapid, easily accessible http://axograph.com/source/abr.html approach to measure hearing threshold levels in auditory brainstem response.
Psychotropic drugs up-regulate the expression of cholesterol transport proteins including ApoE in cultured human CNS- and liver cells
Authors: Vik-Mo Audun O , Fernø Johan , Skrede Silje , Steen Vidar M
Published: August 2009

Background

Disturbances in lipid homeostasis and myelination have been proposed in the pathophysiology of schizophrenia and bipolar disorder. We have previously shown that several antipsychotic and antidepressant drugs increase lipid biosynthesis through activation of the Sterol Regulatory Element-Binding Protein (SREBP) transcription factors, which control the expression of numerous genes involved in fatty acid and cholesterol biosynthesis. The aim of the present proof-of-principle study was to investigate whether such drugs also affect lipid transport and export pathways in cultured human CNS and liver cells.

Results

Quantitative PCR and immunoblotting were used to determine the level of lipid transport genes in human glioblastoma (GaMg) exposed to clozapine, olanzapine, haloperidol or imipramine. The effect of some of these drugs was also investigated in human astrocytoma (CCF-STTG1), neuroblastoma (SH-SY5Y) and hepatocellular carcinoma (HepG2) cells. We found significant transcriptional changes of cholesterol transport genes (ApoE, ABCA1, NPC1, NPC2, NPC1L1), which are predominantly controlled by the Liver X receptor (LXR) transcription factor. The up-regulation was observed after 24 to 48 hours of drug exposure, which is markedly delayed as compared to the drug-induced SREBP-controlled stimulation of lipid biosynthesis seen after 6 hours.

Conclusion

Our data show that stimulation of cellular lipid biosynthesis by amphiphilic psychotropic drugs is followed by a transcriptional activation of cholesterol transport and efflux pathways. Such effects may be relevant for both therapeutic effects and metabolic adverse effects of psychotropic drugs.
Attitudes, norms and controls influencing lifestyle risk factor management in general practice
Authors: Ampt Amanda J , Amoroso Cheryl , Harris Mark F , McKenzie Suzanne H , Rose Vanessa K , Taggart Jane R
Published: August 2009

Background

With increasing rates of chronic disease associated with lifestyle behavioural risk factors, there is urgent need for intervention strategies in primary health care. Currently there is a gap in the knowledge of factors that influence the delivery of preventive strategies by General Practitioners (GPs) around interventions for smoking, nutrition, alcohol consumption and physical activity (SNAP). This qualitative study explores the delivery of lifestyle behavioural risk factor screening and management by GPs within a 45–49 year old health check consultation. The aims of this research are to identify the influences affecting GPs' choosing to screen and choosing to manage SNAP lifestyle risk factors, as well as identify influences on screening and management when multiple SNAP factors exist.

Methods

A total of 29 audio-taped interviews were conducted with 15 GPs and one practice nurse over two stages. Transcripts from the interviews were thematically analysed, and a model of influencing factors on preventive care behaviour was developed using the Theory of Planned Behaviour as a structural framework.

Results

GPs felt that assessing smoking status was straightforward, however some found assessing alcohol intake only possible during a formal health check. Diet and physical activity were often inferred from appearance, only being assessed if the patient was overweight. The frequency and thoroughness of assessment were influenced by the GPs' personal interests and perceived congruence with their role, the level of risk to the patient, the capacity of the practice and availability of time. All GPs considered advising and educating patients part of their professional responsibility. However their attempts to motivate patients were influenced by perceptions of their own effectiveness, with smoking causing the most frustration. Active follow-up and referral of patients appeared to depend on the GPs' orientation to preventive care, the patient's motivation, and cost and accessibility of services to patients.

Conclusion

General practitioner attitudes, normative influences from both patients and the profession, and perceived external control factors (time, cost, availability and practice capacity) all influence management of behavioural risk factors. Provider education, community awareness raising, support and capacity building may improve the uptake of lifestyle modification interventions.
Comparison of rapid tests for detection of rifampicin-resistant Mycobacterium tuberculosis in Kampala, Uganda
Authors: Ogwang Sam , Asiimwe Benon B , Traore Hamidou , Mumbowa Francis , Okwera Alphonse , Eisenach Kathleen D , Kayes Susan , Jones-López Edward C , McNerney Ruth , Worodria William , Ayakaka Irene , Mugerwa Roy D , Smith Peter G , Ellner Jerrold , Joloba Moses L
Published: August 2009

Background

Drug resistant tuberculosis (TB) is a growing concern worldwide. Rapid detection of resistance expedites appropriate intervention to control the disease. Several technologies have recently been reported to detect rifampicin resistant Mycobacterium tuberculosis directly in sputum samples. These include phenotypic culture based methods, tests for gene mutations and tests based on bacteriophage replication. The aim of the present study was to assess the feasibility of implementing technology for rapid detection of rifampicin resistance in a high disease burden setting in Africa.

Methods

Sputum specimens from re-treatment TB patients presenting to the Mulago Hospital National TB Treatment Centre in Kampala, Uganda, were examined by conventional methods and simultaneously used in one of the four direct susceptibility tests, namely direct BACTEC 460, Etest, "in-house" phage test, and INNO- Rif.TB. The reference method was the BACTEC 460 indirect culture drug susceptibility testing. Test performance, cost and turn around times were assessed.

Results

In comparison with indirect BACTEC 460, the respective sensitivities and specificities for detecting rifampicin resistance were 100% and 100% for direct BACTEC and the Etest, 94% and 95% for the phage test, and 87% and 87% for the Inno-LiPA assay. Turn around times ranged from an average of 3 days for the INNO-LiPA and phage tests, 8 days for the direct BACTEC 460 and 20 days for the Etest. All methods were faster than the indirect BACTEC 460 which had a mean turn around time of 24 days. The cost per test, including labour ranged from $18.60 to $41.92 (USD).

Conclusion

All four rapid technologies were shown capable of detecting rifampicin resistance directly from sputum. The LiPA proved rapid, but was the most expensive. It was noted, however, that the LiPA test allows sterilization of samples prior to testing thereby reducing the risk of accidental laboratory transmission. In contrast the Etest was low cost, but slow and would be of limited assistance when treating patients. The phage test was the least reproducible test studied with failure rate of 27%. The test preferred by the laboratory personnel, direct BACTEC 460, requires further study to determine its accuracy in real-time treatment decisions in Uganda.
Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy
Authors: Chiappini Elena , Galli Luisa , Tovo Pier-Angelo , Gabiano Clara , Lisi Catiuscia , Bernardi Stefania , Viganò Alessandra , Guarino Alfredo , Giaquinto Carlo , Esposito Susanna , Badolato Raffaele , Di Bari Cesare , Rosso Raffaella , Genovese Orazio , Masi Massimo , Mazza Antonio , de Martino Maurizio
Published: August 2009

Background

Early highly active antiretroviral therapy (HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking.

Methods

We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range [IQR]:4.21–7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided.

Results

Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71–5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4+ T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4+ T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001).

Conclusion

Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed.
Population normative data for the 10/66 Dementia Research Group cognitive test battery from Latin America, India and China: a cross-sectional survey
Authors: Sosa Ana Luisa , Albanese Emiliano , Prince Martin , Acosta Daisy , Ferri Cleusa P , Guerra Mariella , Huang Yueqin , Jacob KS , de Rodriguez Juan Llibre , Salas Aquiles , Yang Fang , Gaona Ciro , Joteeshwaran AT , Rodriguez Guillermina , de la Torre Gabriela Rojas , Williams Joseph D , Stewart Robert
Published: August 2009

Background

1) To report site-specific normative values by age, sex and educational level for four components of the 10/66 Dementia Research Group cognitive test battery; 2) to estimate the main and interactive effects of age, sex, and educational level by site; and 3) to investigate the effect of site by region and by rural or urban location.

Methods

Population-based cross-sectional one phase catchment area surveys were conducted in Cuba, Dominican Republic, Venezuela, Peru, Mexico, China and India. The protocol included the administration of the Community Screening Instrument for Dementia (CSI 'D', generating the COGSCORE measure of global function), and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) verbal fluency (VF), word list memory (WLM, immediate recall) and recall (WLR, delayed recall) tests. Only those free of dementia were included in the analysis.

Results

Older people, and those with less education performed worse on all four tests. The effect of sex was much smaller and less consistent. There was a considerable effect of site after accounting for compositional differences in age, education and sex. Much of this was accounted for by the effect of region with Chinese participants performing better, and Indian participants worse, than those from Latin America. The effect of region was more prominent for VF and WLM than for COGSCORE and WLR.

Conclusion

Cognitive assessment is a basic element for dementia diagnosis. Age- and education-specific norms are required for this purpose, while the effect of gender can probably be ignored. The basis of cultural effects is poorly understood, but our findings serve to emphasise that normative data may not be safely generalised from one population to another with quite different characteristics. The minimal effects of region on COGSCORE and WLR are reassuring with respect to the cross-cultural validity of the 10/66 dementia diagnosis, which uses only these elements of the 10/66 battery.