bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexible and multistable pattern generation by evolving constrained plastic neurocontrollers
Authors: Hoinville Thierry , Tapia Siles Cecilia , Hénaff Patrick
Published: May 2011

In evolutionary robotics, plastic neural network models proved to be promising for evolving adaptive behaviors. In particular, neurocontrollers incorporating hebbian synapses have been shown to be useful for implementing conflicting sub-behaviors. Numerous interesting complex tasks assume such flexibility. However, those evolved controllers often exhibit behavioral instability, as simulation time is extended beyond the short limit used during evolution. In this paper, we propose constrained plastic models inspired by neural homeostasis phenomena, in order to evolve flexible and stable pattern generators for single-legged locomotion. Comparative results show that constrained controllers perform better than unconstrained ones in both terms of evolvability and behavioral stability. Functional analyses of the best evolved controller unveil the adaptivity, robustness and homeostasis arising from the statically constrained plasticity. Interestingly, homeostasis evolved implicitly without relying on any active homeostatic mechanisms and is implemented through hebbian plasticity, usually considered destabilizing.
Big Questions Facing Vocational Psychology: A Cognitive Information Processing Perspective
Authors: Reardon Robert C. , Lenz Janet G. , Sampson James P. , Peterson Gary W.
Published: May 2011

This article draws upon the authors’ experience in developing cognitive information processing theory in order to examine three important questions facing vocational psychology and assessment: (a) Where should new knowledge for vocational psychology come from? (b) How do career theories and research find their way into practice? and (c) What is the nature of career development and vocational choice in a global economy? Topics include the interdisciplinary nature of knowledge in this field, the extensive information provided by established career theories and applications, the ongoing need to inform practice through theory and research, the transformation and dissemination of knowledge from the laboratory to the field, and the common themes among education and work issues in a global economy.
New Cross-Cultural Perspectives on Marriage Transactions
Authors: Huber Brad R. , Danaher William F. , Breedlove William L.
Published: May 2011

This article refines and extends previous cross-cultural research on marriage transactions (e.g., bride wealth, dowry). The authors begin by expanding the standard cross-cultural typology of marriage transactions. They identify six additional kinds of transactions (e.g., groom wealth, groom service) and show that many societies of the Human Relations Area Files (HRAF) probability sample have two or more types of transactions. Next, the authors take a Darwinian approach to marriage transactions. Differences in male and female reproductive strategies account for the general pattern of the bride’s family materially benefitting from marriage at the expense of the groom’s family. Kin selection theory explains why wealth devolves from the parents of the couple to the bride and groom. Finally, the authors examine evidence that the type of kin relied on by members of a society and the prevalence of polygyny also influence marriage transactions in predictable ways.
Modelling the dependence of goals scored by opposing teams in international soccer matches
Authors: McHale Ian , Scarf Phil
Published: May 2011

This paper presents models for the number of goals scored by opposing teams in international soccer matches. The bivariate discrete distributions employed are defined in terms of the marginal distributions and a dependence copula. This copula representation allows dependence in the bivariate distribution to be modelled in a flexible manner by specifying a suitable family of copula functions and fitting this to the bivariate data using maximum likelihood. Marginal means are modelled with match covariates. The nature of the dependence in the number of goals scored is complex, and we develop the idea that the strength of dependence depends on the competitive balance of a match. Our analysis suggests that for games between closely matched teams, the overall dependence is low, and that the dependence becomes increasingly negative as the competitiveness of a match decreases. In this way, we relate dependence to competitive balance and suggest a method to measure the latter quantity. The models developed here may also offer better forecasts than those offered by match outcome models with independent marginal distributions.
Rosiglitazone improves endothelial function in patients with type 2 diabetes treated with insulin
Authors: Naka Katerina K , Papathanassiou Katerina , Bechlioulis Aris , Pappas Konstantinos , Kazakos Nikolaos , Kanioglou Chryssanthi , Papafaklis Michail I , Kostoula Aggeliki , Vezyraki Patra , Makriyiannis Demetrios , Tsatsoulis Agathocles , Michalis Lampros K
Published: May 2011

An increased incidence of myocardial infarction with rosiglitazone in patients with type 2 diabetes mellitus (T2DM) has been reported. This study aimed to assess the effect of rosiglitazone on endothelial function, assessed by flow-mediated dilation (FMD), in 34 patients with advanced T2DM treated with insulin without known cardiovascular disease. Patients were randomised into two groups: no additional treatment was given in 17 patients, while 17 patients were given rosiglitazone for 6 months. Addition of rosiglitazone significantly reduced glycosylated haemoglobin (HbA1c) ( p < 0.0005) and fasting glucose ( p < 0.05) and improved FMD ( p < 0.005). No significant changes were observed in the insulin-only group. The single independent predictor of FMD improvement was rosiglitazone treatment ( p = 0.048). These results show that, in patients with advanced T2DM treated with insulin, addition of rosiglitazone may have a beneficial effect on endothelial function. Further research is needed to investigate why this beneficial effect does not translate into improved cardiovascular prognosis in these patients.
Multiple Health Behavior Change: Game On or Time Out?
Authors: Terre Lisa
Published: May 2011

This review discusses evidence-based perspectives on multiple health behavior change and related interventions. Future directions for inquiry and practice also are addressed.
Suboptimal Exercise Compliance: Common Barriers to an Active Lifestyle and Counseling Strategies to Overcome Them
Authors: Brinks Jenna , Franklin Barry A.
Published: May 2011

Adherence to a structured exercise program provides numerous health benefits, including reductions in body weight, fat stores, and blood pressure, improved blood glucose management and lipid/lipoprotein profiles, increased cardiorespiratory fitness, decreased cardiovascular risk, and enhanced psychosocial well-being. Despite these benefits, many individuals find it difficult to comply with a regular exercise program, predisposing them to an increased risk of chronic diseases and other medical conditions. Several barriers to participation in structured exercise, including time and financial constraints, psychosocial factors, and physical limitations, contribute to low adherence rates. Accordingly, health care professionals should use varied counseling strategies to assist their patients in overcoming habitual physical inactivity and our increasingly hypokinetic lifestyle. Motivational interviewing, goal setting, using stages of readiness to change, and identifying physical/psychosocial limitations are effective ways for helping patients to achieve the health and fitness benefits of structured exercise, increased lifestyle physical activity, or both.
Infection control nurses’ perceptions of managing MRSA in the community
Authors: Randle Jacqueline , Bellamy Elaine
Published: May 2011

In the United Kingdom (UK), the majority of hospitalised patients colonised with meticillin resistant Staphylococcus aureus (MRSA) prior to or on admission to hospital are prescribed decolonisation treatment and isolated with appropriate precautions to reduce the risk of cross-transmission. However, MRSA colonisation in patients who have not completed decolonisation therapy does not prevent discharge or transfer to community healthcare facilities and current guidelines do not recommend routine community treatment and follow-up of patients. This qualitative study examines the perceptions of six senior infection prevention and control nurses in relation to the management of MRSA colonisation in the community. Data were collected using semi-structured interviews, and findings suggest that gaps exist in current service provision for patients colonised with MRSA who are discharged to community healthcare settings. Respondents perceived that this was due to a number of

factors including: practice being shaped by targets, compliance with guidelines, and the split in hospital and community providers. We suggest that current guidelines should be modified to provide follow-up for patients colonised with MRSA who are discharged to community healthcare settings.
Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs
Authors: Ulrichts Hans , Silence Karen , Schoolmeester Anne , de Jaegere Peter , Rossenu Stefaan , Roodt Jan , Priem Sofie , Lauwereys Marc , Casteels Peter , Van Bockstaele Femke , Verschueren Katrien , Stanssens Patrick , Baumeister Judith , Holz Josefin-Beate
Published: May 2011

Neutralizing the interaction of the platelet receptor gpIb with VWF is an attractive strategy to treat and prevent thrombotic complications. ALX-0081 is a bivalent Nanobody which specifically targets the gpIb-binding site of VWF and interacts avidly with VWF. Nanobodies are therapeutic proteins derived from naturally occurring heavy-chain–only Abs and combine a small molecular size with a high inherent stability. ALX-0081 exerts potent activity in vitro and in vivo. Perfusion experiments with blood from patients with acute coronary syndrome on standard antithrombotics demonstrated complete inhibition of platelet adhesion after addition of ALX-0081, while in the absence of ALX-0081 residual adhesion was observed. In a baboon efficacy and safety model measuring acute thrombosis and surgical bleeding, ALX-0081 showed a superior therapeutic window compared with marketed antithrombotics. Pharmacokinetic and biodistribution experiments demonstrated target-mediated clearance of ALX-0081, which leads to a self-regulating disposition behavior. In conclusion, these preclinical data demonstrate that ALX-0081 combines a high efficacy with an improved safety profile compared with currently marketed antithrombotics. ALX-0081 has entered clinical development.
Self-reported fever, treatment actions and malaria infection prevalence in the northern states of Sudan
Authors: Elmardi Khalid A , Noor Abdisalan M , Githinji Sophie , Abdelgadir Tareg M , Malik ElFatih M , Snow Robert W
Published: May 2011

Background

The epidemiology of fevers and their management in areas of low malaria transmission in Africa is not well understood. The characteristics of fever, its treatment and association with infection prevalence from a national household sample survey in the northern states of Sudan, an area that represents historically low parasite prevalence, are examined in this study.

Methods

In October-November 2009, a cluster sample cross-sectional household malaria indicator survey was undertaken in the 15 northern states of the Sudan. Data on household assets and individual level information on age, sex, whether the individual had a fever in the last 14 days and on the day of survey, actions taken to treat the fever including diagnostic services and drugs used and their sources were collected. Consenting household members were asked to provide a finger-prick blood sample and examined for malaria parasitaemia using a rapid diagnostic test (RDT). All proportions and odds ratios were weighted and adjusted for clustering.

Results

Of 26,471 respondents 19% (n = 5,299) reported a history of fever within the last two weeks prior to the survey and 8% had fever on the day of the survey. Only 39% (n = 2,035) of individuals with fever in last two weeks took any action, of which 43% (n = 875) were treated with anti-malarials. About 44% (n = 382) of malaria treatments were done using the nationally recommended first-line therapy artesunate+sulphadoxine-pryrimethamine (AS+SP) and 13% (n = 122) with non-recommended chloroquine or SP. Importantly 33.9% (n = 296) of all malaria treatments included artemether monotherapy, which is internationally banned for the treatment of uncomplicated malaria. About 53% of fevers had some form of parasitological diagnosis before treatment. On the day of survey, 21,988 individuals provided a finger-prick blood sample and only 1.8% were found positive forPlasmodium falciparum. Infection prevalence was higher among individuals who had fever in the last two weeks (OR = 3.4; 95%CI = 2.6 - 4.4, p < 0.001) or reported fever on the day of survey (OR = 6.2; 95%CI = 4.4 - 8.7, p < 0.001) compared to those without a history of fever.

Conclusion

Across the northern states of the Sudan, the period prevalence of fever is low. The proportion of fevers that are likely to be malaria is very low. Consequently, parasitological diagnosis of all fevers before treatment is an appropriate strategy for malaria case-management. Improved regulation and supervision of health workers is required to increase the use of diagnostics and remove the practice of prescribing artemisinin monotherapy.
Porous Organic Nanolayers for Coating of Solid-state Devices
Authors: Vidyala Sri D , Asghar Waseem , Iqbal Samir M
Published: May 2011

Background

Highly hydrophobic surfaces can have very low surface energy and such low surface energy biological interfaces can be obtained using fluorinated coatings on surfaces. Deposition of biocompatible organic films on solid-state surfaces is attained with techniques like plasma polymerization, biomineralization and chemical vapor deposition. All these require special equipment or harsh chemicals. This paper presents a simple vapor-phase approach to directly coat solid-state surfaces with biocompatible films without any harsh chemical or plasma treatment. Hydrophilic and hydrophobic monomers were used for reaction and deposition of nanolayer films. The monomers were characterized and showed a very consistent coating of 3D micropore structures.

Results

The coating showed nano-textured surface morphology which can aid cell growth and provide rich molecular functionalization. The surface properties of the obtained film were regulated by varying monomer concentrations, reaction time and the vacuum pressure in a simple reaction chamber. Films were characterized by contact angle analysis for surface energy and with profilometer to measure the thickness. Fourier Transform Infrared Spectroscopy (FTIR) analysis revealed the chemical composition of the coated films. Variations in the FTIR results with respect to different concentrations of monomers showed the chemical composition of the resulting films.

Conclusion

The presented approach of vapor-phase coating of solid-state structures is important and applicable in many areas of bio-nano interface development. The exposure of coatings to the solutions of different pH showed the stability of the coatings in chemical surroundings. The organic nanocoating of films can be used in bio-implants and many medical devices.
Validation of the japanese version of the sarcoidosis health questionnaire: A cross-sectional study
Authors: Tanizawa Kiminobu , Handa Tomohiro , Nagai Sonoko , Oga Toru , Kubo Takeshi , Ito Yutaka , Watanabe Kizuku , Aihara Kensaku , Chin Kazuo , Mishima Michiaki , Izumi Takateru
Published: May 2011

Background

Although impaired health-related quality of life (HRQOL) has been reported in patients with sarcoidosis, there is currently no sarcoidosis-specific questionnaire in Japan. The 29-item Sarcoidosis Health Questionnaire (SHQ), originally developed in the United States, is the only sarcoidosis-specific HRQOL questionnaire currently available. The primary aim of this study was to develop and validate a Japanese version of the SHQ.

Findings

The SHQ was translated into Japanese following the forward-backward procedure. The reliability and validity of the Japanese version of the SHQ were examined. One hundred twenty-two Japanese patients with biopsy-proven sarcoidosis were evaluated by the SHQ, the Medical Outcomes Study 36-item short form (SF-36), the St. George's Respiratory Questionnaire (SGRQ), chest radiography, an electrocardiogram, laboratory blood tests, pulmonary function tests, an echocardiogram, and assessments of dyspnea and depressive symptoms. The SHQ was found to have acceptable levels of internal consistency (Cronbach's coefficient α values = 0.68 to 0.91). SHQ scores correlated significantly with scores on the SF-36 and SGRQ. The domain or total scores on the SHQ also significantly correlated with serum levels of the soluble interleukin-2 receptor, the percentage of the predicted forced vital capacity, pulmonary arterial systolic pressure, dyspnea, and depressive symptoms. Also, the SHQ scores of patients who had one or two organ systems affected by sarcoidosis were significantly different from those of patients who had three or more organ systems involvement.

Conclusions

The Japanese version of the SHQ can be used to assess the HRQOL of patients with sarcoidosis.
Socio-demographic association of multiple modifiable lifestyle risk factors and their clustering in a representative urban population of adults: a cross-sectional study in Hangzhou, China
Authors: Lv Jun , Liu Qingmin , Ren Yanjun , Gong Ting , Wang Shengfeng , Li Liming ,   the Community Interventions for Health (CIH) collaboration
Published: May 2011

Background

To plan long-term prevention strategies and develop tailored intervention activities, it is important to understand the socio-demographic characteristics of the subpopulations at high risk of developing chronic diseases. This study aimed to examine the socio-demographic characteristics associated with multiple lifestyle risk factors and their clustering.

Methods

We conducted a simple random sampling survey to assess lifestyle risk factors in three districts of Hangzhou, China between 2008 and 2009. A two-step cluster analysis was used to identify different health-related lifestyle clusters based on tobacco use, physical activity, fruit and vegetable consumption, and out-of-home eating. Multinomial logistic regression was used to model the association between socio-demographic factors and lifestyle clusters.

Results

A total of 2016 eligible people (977 men and 1039 women, ages 18-64 years) completed the survey. Three distinct clusters were identified from the cluster analysis: an unhealthy (UH) group (25.7%), moderately healthy (MH) group (31.1%), and healthy (H) group (43.1%). UH group was characterised by a high prevalence of current daily smoking, a moderate or low level of PA, low FV consumption with regard to the frequency or servings, and more occurrences of eating out. H group was characterised by no current daily smoking, a moderate level of PA, high FV consumption, and the fewest times of eating out. MH group was characterised by no current daily smoking, a low or high level of PA, and an intermediate level of FV consumption and frequency of eating out. Men were more likely than women to have unhealthy lifestyles. Adults aged 50-64 years were more likely to live healthy lifestyles. Adults aged 40-49 years were more likely to be in the UH group. Adults whose highest level of education was junior high school or below were more likely to be in the UH group. Adults with a high asset index were more likely to be in the MH group.

Conclusions

This study suggests that Chinese urban people who are middle-aged, men, and less educated are most likely to be part of the cluster with a high-risk profile. Those groups will contribute the most to the future burden of major chronic disease and should be targeted for early prevention programs.
Loss of the receptor tyrosine kinase Axl leads to enhanced inflammation in the CNS and delayed removal of myelin debris during Experimental Autoimmune Encephalomyelitis
Authors: Weinger Jason G , Brosnan Celia F , Loudig Olivier , Goldberg Michael F , Macian Fernando , Arnett Heather A , Prieto Anne L , Tsiperson Vladislav , Shafit-Zagardo Bridget
Published: May 2011

Background

Axl, together with Tyro3 and Mer, constitute the TAM family of receptor tyrosine kinases. In the nervous system, Axl and its ligand Growth-arrest-specific protein 6 (Gas6) are expressed on multiple cell types. Axl functions in dampening the immune response, regulating cytokine secretion, clearing apoptotic cells and debris, and maintaining cell survival. Axl is upregulated in various disease states, such as in the cuprizone toxicity-induced model of demyelination and in multiple sclerosis (MS) lesions, suggesting that it plays a role in disease pathogenesis. To test for this, we studied the susceptibility of Axl-/- mice to experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis.

Methods

WT and Axl-/- mice were immunized with myelin oligodendrocyte glycoprotein (MOG)35-55peptide emulsified in complete Freund's adjuvant and injected with pertussis toxin on day 0 and day 2. Mice were monitored daily for clinical signs of disease and analyzed for pathology during the acute phase of disease. Immunological responses were monitored by flow cytometry, cytokine analysis and proliferation assays.

Results

Axl-/- mice had a significantly more severe acute phase of EAE than WT mice. Axl-/- mice had more spinal cord lesions with larger inflammatory cuffs, more demyelination, and more axonal damage than WT mice during EAE. Strikingly, lesions in Axl-/- mice had more intense Oil-Red-O staining indicative of inefficient clearance of myelin debris. Fewer activated microglia/macrophages (Iba1+) were found in and/or surrounding lesions in Axl-/- mice relative to WT mice. In contrast, no significant differences were noted in immune cell responses between naïve and sensitized animals.

Conclusions

These data show that Axl alleviates EAE disease progression and suggests that in EAE Axl functions in the recruitment of microglia/macrophages and in the clearance of debris following demyelination. In addition, these data provide further support that administration of the Axl ligand Gas6 could be therapeutic for immune-mediated demyelinating diseases.
From the Western Alps across Central Europe: Postglacial recolonisation of the tufa stream specialist Rhyacophila pubescens (Insecta, Trichoptera)
Authors: Engelhardt Christine HM , Haase Peter , Pauls Steffen U
Published: May 2011

Background

Dispersal rates, i.e. the effective number of dispersing individuals per unit time, are the product of dispersal capacity, i.e. a species physiological potential for dispersal, dispersal behaviour, i.e. the decision to leave a habitat patch in favour of another, and connectivity of occupied habitat. Thus, dispersal of species that are highly specialised to a certain habitat is limited by habitat availability. Species inhabiting very stable environments may also adopt a sedentary life-style. Both factors should lead to strong genetic differentiation in highly specialised species inhabiting stable environments. These two factors apply to our model speciesRhyacophila pubescensa highly specialised freshwater insect that occurs in tufa springs, a very stable habitat.

Results

We examined the genetic population structure and phylogeography using range-wide mtCOI sequence and AFLP data from 333 individuals ofR. pubescens. We inferred the location of Pleistocene refugia and postglacial colonisation routes ofR. pubescens, and examined ongoing local differentiation. Our results indicate intraregional differentiation with a high number of locally endemic haplotypes, that we attributed to habitat specificity and low dispersal rates ofR. pubescens. We observed high levels of genetic diversity south of the Alps and genetic impoverishment north of the Alps. Estimates of migrants placed the refugium and the source of the colonisation in the Dauphiné Alps (SW Alps).

Conclusions

This is the first example of an aquatic insect with a colonisation route along the western margin of the Alps to the Central European highlands. The study also shows that specialisation to a stable environment may have promoted a behavioural shift to decreased dispersal rates, leading to stronger local population differentiation than in less specialised aquatic insects. Alternatively, the occurrence of highly specialised tufa spring habitats may have been more widespread in the past, leading to range regression and fragmentation among present dayR. pubescenspopulations.
Monoclonal antibody-based serological methods for detection of Cucumber green mottle mosaic virus
Authors: Shang Haili , Xie Yan , Zhou Xueping , Qian Yajuan , Wu Jianxiang
Published: May 2011

Background

Cucumber green mottle mosaic virus (CGMMV), a member of the genusTobamovirus, can be transmitted by seeds and infects many cucurbit species, causing serious yield losses in cucumber and watermelon plants. In this paper, five serological methods including antigen-coated plate enzyme-linked immunosorbent assay (ACP-ELISA), triple antibody sandwich enzyme-linked immunosorbent assay (TAS-ELISA), Dot-immunobinding assay (DBIA), direct tissue blot immunoassay (DTBIA) and immunocapture reverse transcriptase polymerase chain reaction (IC-RT-PCR) were described for detection and diagnosis of CGMMV.

Results

Using the purified CGMMV particles as immunogens, six murine monoclonal antibodies (MAbs) were produced. Five serological methods were established using the MAb 4H1 and detection sensitivity was compared using purified preparations and infected-plant tissue extracts. The detection sensitivity of ACP-ELISA was 0.16 ng of purified CGMMV, whereas TAS-ELISA was more sensitive than ACP-ELISA with a minimum detection of 0.04 ng of purified CGMMV. The sensitivities of TAS-ELISA and DBIA were similar for detecting CGMMV in infected-plant tissue extracts, and were four times higher than ACP-ELISA. The IC-RT-PCR was the most sensitive method, which could detect as little as 0.1 pg of purified virus. The detection sensitivity of IC-RT-PCR for CGMMV-infected plant tissues was about 400 times higher than that of TAS-ELISA and DBIA.

Conclusions

The established ACP-ELISA, TAS-ELISA, DBIA and DTBIA are suitable for routine CGMMV detection of large-scale samples in the field survey, while IC-RT-PCR is more sensitive and suitable for acquiring information about the viral genome.
Design and evaluation of a multi-epitope assembly Peptide (MEAP) against herpes simplex virus type 2 infection in BALB/c mice
Authors: Wang Xingsheng , Xie Guangyan , Liao Jianming , Yin Dengke , Guan Wenyan , Pan Mingjie , Li Jingnian , Li Yuexi
Published: May 2011

Background

Human herpes simplex virus (HSV) 1 and 2 causes oral, ocular, or genital infections, which remains a significant health problem worldwide. HSV-1 and -2 infections in humans range from localized skin infections of the oral, ocular, and genital regions to severe and often disseminated infections in immunocompromised hosts. Epitope based vaccination is a promising mean to achieve protective immunity and to avoid infections with Human herpes simplex virus type 2 (HSV-2).

Methods

The twelve selected epitopes, six B cell epitopes from different glycoprotein of HSV-2 (amino acid residues 466-473 (EQDRKPRN) from envelope glycoprotein B, 216-223 (GRTDRPSA) from C, 6-18 (DPSLKMADPNRFR) from D, 483-491 (DPPERPDSP) from E, 572-579 (EPPDDDDS) from G and 286-295 (CRRRYRRPRG) from I glycoprotein of HSV-2), four CD4+T cell epitopes (amino acid residues 21-28 (NLPVLDQL) from D, 162-177 (KDVTVSQVWFGHRYSQ) from B, 205-224 (KAYQQGVTVDSIGMLPRFIP) from D and 245-259 (KPPYTSTLLPPELSD) from D) and two CD8+T cell epitopes (amino acid residues 10-20 (KMADPNRFRGK) from D and 268-276 (ALLEDPAGT) from D), are responsible for the elicitation of the neutralizing antibodies and cytotoxic T lymphocytes (CTLs) that impart protective immunity to the host. In this study, all above epitopes were inserted into the extracellular fragment (amino acid residues 1-290) of HSV-2 glycoprotein D to construct multi-epitope assembly peptides (MEAPs) by replacing some non-epitope amino acid sequences. The epitope independency of the MEAPs was predicted by three-dimensional software algorithms. The gene of the selected MEAP was expressed inE.coliBL21(DE3), and its protective efficacy against HSV-2 infection was assessed in BALB/c mice.

Results

The MEAP, with each inserted epitopes independently displayed on the molecule surface, was selected as candidate proteins. The results showed that the MEAP was highly immunogenic and could elicit high titer neutralizing antibodies and cell-mediated immune responses.

Conclusions

The MEAP provided complete protection against infection with HSV-2 in mice, which indicates that it might be a potential candidate vaccine against HSV-2.
Laparoscopic insertion of pelvic tissue expander to prevent radiation enteritis prior to radiotherapy for prostate cancer
Authors: McKay Gary D , Wong Karen , Kozman Daniel R
Published: May 2011

Radiation enteritis is a significant complication of external beam radiotherapy (EBRT) to the pelvis, particularly in patients having high dose radiotherapy (>80 Gy) and in those with a low pelvic peritoneal reflection allowing loops of small bowel to enter the radiation field. Laparoscopic insertion and subsequent removal of a pelvic tissue expander before and after external beam radiotherapy is a relatively convenient, safe and effective method for displacing loops of bowel out of the pelvis. We report on a patient with prostate cancer who ordinarily would not have been a candidate for EBRT due to loops of bowel low in the pelvis. With laparoscopic insertion and subsequent removal of a tissue expander, he was able to have radiotherapy to the prostate without developing radiation enteritis.
Degenerative processes in bioprosthetic mitral valves in juvenile pigs
Authors: Honge Jesper L , Funder Jonas A , Pedersen Torben B , Kronborg Mads B , Hasenkam J Michael
Published: May 2011

Background

Glutaraldehyde-treated bioprosthetic heart valves are commonly used for replacement of diseased heart valves. However, calcification and wear limit their durability, and the development of new and improved bioprosthetic valve designs is needed and must be evaluated in a reliable animal model. We studied glutaraldehyde-treated valves 6 months after implantation to evaluate bioprosthetic valve complications in the mitral position in juvenile pigs.

Materials

The study material comprised eight, 5-month old, 60-kg pigs. All pigs received a size 27, glutaraldehyde-treated, stented, Carpentier-Edwards S.A.V. mitral valve prosthesis. After six months, echocardiography was performed, and the valves explanted for gross examination, high resolution X-ray, and histological evaluation.

Results

Five pigs survived the follow-up period. Preexplant echocardiography revealed a median peak and mean velocity of 1.61 m/s (range: 1.17-2.00) and 1.20 (SD = ±0.25), respectively, and a median peak and mean pressure difference of 10.42 mmHg (range: 5.83-16.55) and 6.51 mmHg (SD = ±2.57), respectively. Gross examination showed minor thrombotic depositions at two commissures in two valves and at all three commissures in three valves. High resolution X-ray imaging revealed different degrees of calcification in all explanted valves, primarily in the commissural and belly areas. In all valves, histological evaluation demonstrated various degrees of fibrous sheath formation, limited immunological infiltration, and no overgrowth of host endothelium.

Conclusions

Bioprosthetic glutaraldehyde-treated mitral valves can be implanted into the mitral position in pigs and function after 6 months. Echocardiographic data, calcification, and histological examinations were comparable to results obtained in sheep models and human demonstrating the suitability of the porcine model.
Pharmacological strategies to reduce pruritus during postoperative epidural analgesia after lumbar fusion surgery - a prospective randomized trial in 150 patients
Authors: Gulle Eva , Skärvinge Carola , Runberg Karin , Robinson Yohan , Olerud Claes
Published: May 2011

Background

Epidural analgesia with bupivacain, epinephrine and fentanyl provides excellent pain control after lumbar fusion surgery, but pruritus and motor block are frequent side effects. Theoretically epidural ropivacain combined with oral oxycodone could decrease the incidence of these side effects. The two regimens were compared in a prospective randomized trial.

Patients and methods

150 patients (87 women) treated with posterior instrumented lumbar fusion were included. The mean age was 51 +/- 11 years. 76 were randomized to bupivacain, epinephrine and fentanyl (group B) and 74 to ropivacain and oxycodone (group R). Pruritus, motor block and pain were measured 6 hours after surgery, thereafter 6 times per day for 5 days. Any pain breakthrough episode was registered whenever it occurred.

Results

The epidural treatment could be performed in 143 patients (72 in group B and 71 in group R). Disturbing pruritus occurred in 53 patients in group B compared to 12 in group R (p < 0.0001). Motor blockade was most frequent on day 1, occurring in 45% of the patients with no difference between the groups. Both regimes gave good pain control with average VAS under 40, but the pain relief was statistically better in group B. The number of pain breakthrough episodes did not differ between the groups.

Conclusions

Pruritus could be reduced with a combination of epidural ropivacain and oral oxycodone, at the price of a slightly higher pain level. Ropivacaine was not found to be superior to bupivacaine with regard to motor blocks.
The net cost of incorporating resistance testing into HIV/AIDS treatment in South Africa: a Markov model with primary data
Authors: Rosen Sydney , Long Lawrence , Sanne Ian , Stevens Wendy S , Fox Matthew P
Published: May 2011

Background

Current guidelines for providing antiretroviral therapy (ART) in South Africa's public sector programme call for switching patients from first‐line to second‐line treatment upon virologic failure as indicated by two consecutive viral loads above 5000 copies/ml, but without laboratory evidence of viral resistance. We modelled the net cost of adding resistance testing for patients with virological failure and retaining patients without resistance on first‐line therapy, rather than switching all failures to second‐line therapy.

Methods

Costs were estimated for three scenarios: routine maintenance (standard care without resistance testing, switch all failures to second line); resistance testing (resistance test for patients with failure, switch those with resistance); and limited testing (resistance test for patients with failure in the first three years, switch those with resistance). A Markov model was used to estimate the cost of each arm over five years after first line initiation. Rates of treatment failure, viral resistance and treatment costs were estimated with primary data from a large HIV treatment cohort at a public facility in Johannesburg. Future costs were discounted at 3%.

Results

Virological failure rates over five years were 19.8% in routine maintenance and 20.2% in resistance testing and limited testing; 16.8% and 11.4% of failures in routine and limited testing, respectively, did not have any resistance mutations, resulting in 3.1% and 2.0% fewer patients switching to second‐line ART by the end of five years. Treatment costs were estimated at US$526 and $1268 per patient per year on first‐line and second‐line therapy, respectively; a resistance test cost $242. The total average cost per patient over five years was $2780 in routine maintenance; $2775 in resistance testing; and $2763 in limited testing.

Conclusions

Incorporating resistance testing into treatment guidelines in South Africa is potentially cost‐neutral and can identify other reasons for failure, conserve treatment options, and generate information about emerging resistance patterns.
Randomized, Double-Blind, Placebo-Controlled, Phase II Trial of Sorafenib and Erlotinib or Erlotinib Alone in Previously Treated Advanced Non–Small-Cell Lung Cancer
Authors: Spigel David R. , Burris Howard A. , Greco F. Anthony , Shipley Dianna L. , Friedman Elke K. , Waterhouse David M. , Whorf Robert C. , Mitchell R. Brian , Daniel Davey B. , Zangmeister Jeffrey , Bass J. David , Hainsworth John D.
Published: May 2011

Purpose

Sorafenib, an oral multikinase inhibitor, has shown preliminary activity in non–small-cell lung cancer (NSCLC). Patients with advanced NSCLC were treated with erlotinib with or without sorafenib in this multicenter phase II trial.

Patients and Methods

Key eligibility criteria included the following: stage IIIB or IV NSCLC; one to two prior regimens; Eastern Cooperative Oncology Group performance status of 0 to 2; and measurable disease. Patients were randomly assigned 2:1 to sorafenib (400 mg orally twice a day) plus erlotinib (150 mg orally daily) or placebo plus erlotinib and stratified by squamous/nonsquamous histology and prior bevacizumab. Treatment efficacy, measured by progression-free survival (PFS) and overall response rate (ORR), was compared. Treatment of 168 patients allowed detection of 40% improvement in the historical PFS of 2.2 months with single-agent erlotinib.

Results

One hundred sixty-eight patients enrolled from February 2008 to February 2009. Clinical characteristics of the two groups were similar. ORRs for sorafenib/erlotinib and placebo/erlotinib were 8% and 11%, respectively (P = .56); disease control rates were 54% and 38%, respectively (P = .056). Median PFS was 3.38 months for sorafenib/erlotinib versus 1.94 months for placebo/erlotinib (hazard ratio, 0.86; 95% CI, 0.60 to 1.22; P = .196). Seventy-two patients consented to analyses of tumor epidermal growth factor receptor (EGFR). In 67 patients with EGFR wild-type (WT) tumors, median PFS was 3.38 months for sorafenib/erlotinib versus 1.77 months for placebo/erlotinib (P = .018); median overall survival (OS) was 8 months for sorafenib/erlotinib versus 4.5 months for placebo/erlotinib (P = .019). An OS advantage for sorafenib/erlotinib was suggested among 43 patients with fluorescent in situ hybridization (FISH) EGFR-negative tumors (P = .064). Both regimens were tolerable, with modest toxicity increase with sorafenib.

Conclusion

Although there was little difference in ORR or PFS, subset analyses in EGFR WT and EGFR FISH–negative patients suggest a benefit for the combination of erlotinib/sorafenib compared with single-agent erlotinib with respect to PFS and OS.
Effect of Amifostine on Survival Among Patients Treated With Radiotherapy: A Meta-Analysis of Individual Patient Data
Authors: Bourhis Jean , Blanchard Pierre , Maillard Emilie , Brizel David M. , Movsas Benjamin , Buentzel Jens , Langendijk Johannes A. , Komaki Ritsuko , Swan Leong Swan , Levendag Peter , Pignon Jean Pierre
Published: May 2011

Purpose

Controversy exists regarding whether or not amifostine might reduce the efficacy of cancer treatment. The aim of this meta-analysis was to evaluate the impact of amifostine on overall survival (OS) and progression-free survival (PFS) in patients treated with radiotherapy or chemoradiotherapy.

Material and Methods

Updated data from individual patients with non–small-cell lung cancer, head and neck squamous cell carcinoma, and pelvic cancer treated with radiotherapy or chemoradiotherapy and randomly assigned to amifostine or not were included. The primary end point was OS.

Results

Twenty-two randomized trials (2,279 patients) were potentially eligible. Data were available for 16 trials (1,554 patients), but four trials (435 patients) were excluded after data checking. Ultimately 12 trials and 1,119 patients were analyzed. A total of 431 patients were treated with radiotherapy alone (three trials), and 688 patients were treated with chemoradiotherapy (nine trials). Thirty-three percent of patients had lung cancers, 65% had head and neck cancers, and 2% had pelvic carcinomas. Ninety-one percent of patients had locally advanced disease (early stage, 9%). Median follow-up was 5.2 years. The hazard ratio (HR) of death was 0.98 (95% CI, 0.84 to 1.14; P = .78). On the basis of 11 trials (1,091 patients), the HR of progression, relapse, or death was 1.05 (95% CI, 0.90 to 1.22; P = .53). The tests for heterogeneity were not significant (P ≥ .73), and there was no significant variation of treatment effect according to sex, age, tumor site, stage, histology, locoregional treatment, or type of administration for either end point.

Conclusion

Amifostine did not reduce OS and PFS in patients treated with radiotherapy or chemoradiotherapy.
Prognostic Significance ofASXL1Mutations in Patients With Myelodysplastic Syndromes
Authors: Thol Felicitas , Friesen Inna , Damm Frederik , Yun Haiyang , Weissinger Eva M. , Krauter Jürgen , Wagner Katharina , Chaturvedi Anuhar , Sharma Amit , Wichmann Martin , Göhring Gudrun , Schumann Christiane , Bug Gesine , Ottmann Oliver , Hofmann Wolf-Karsten , Schlegelberger Brigitte , Heuser Michael , Ganser Arnold
Published: May 2011

Purpose

To study the incidence and prognostic impact of mutations in Additional sex comb-like 1 (ASXL1) in a large cohort of patients with myelodysplastic syndrome (MDS).

Patients, Materials, and Methods

Overall, 193 patients with MDS and 65 healthy volunteers were examined for ASXL1 mutations by direct sequencing and for expression levels of ASXL1. The prognostic impact of ASXL1 mutation and expression levels was evaluated in the context of other clinical and molecular prognostic markers.

Results

Mutations in ASXL1 occurred with a frequency of 20.7% in MDS (n = 40 of 193) with 70% (n = 28) of mutations being frameshift mutations and 30% (n = 12) being heterozygous point mutations leading to translational changes. ASXL1 mutations were correlated with an intermediate-risk karyotype (P = .002) but not with other clinical parameters. The presence of ASXL1 mutations was associated with a shorter overall survival for frameshift and point mutations combined (hazard ratio [HR], 1.744; 95% CI, 1.08 to 2.82; P = .024) and for frameshift mutations only (HR, 2.06; 95% CI, 1.21 to 3.50; P = .008). ASXL1 frameshift mutations were associated with a reduced time to progression of acute myeloid leukemia (AML; HR 2.35; 95% CI, 1.17 to 4.74; P = .017). In multivariate analysis, when considering karyotype, transfusion dependence, and IDH1 mutation status, ASXL1 frameshift mutations remained an independent prognostic marker in MDS (overall survival: HR, 1.85; 95% CI, 1.03 to 3.34; P = .040; time to AML progression: HR, 2.39; 95% CI, 1.12 to 5.09; P = .024).

Conclusion

These results suggest that ASXL1 mutations are frequent molecular aberrations in MDS that predict an adverse prognostic outcome. Screening of patients for ASXL1 mutations might be useful for clinical risk stratification and treatment decisions in the future.
Phase I Study of Oral Azacitidine in Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, and Acute Myeloid Leukemia
Authors: Garcia-Manero Guillermo , Gore Steven D. , Cogle Christopher , Ward Renee , Shi Tao , MacBeth Kyle J. , Laille Eric , Giordano Heidi , Sakoian Sarah , Jabbour Elias , Kantarjian Hagop , Skikne Barry
Published: May 2011

Purpose

To determine the maximum-tolerated dose (MTD), safety, pharmacokinetic and pharmacodynamic profiles, and clinical activity of an oral formulation of azacitidine in patients with myelodysplastic syndromes (MDSs), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML).

Patients and Methods

Patients received 1 cycle of subcutaneous (SC) azacitidine (75 mg/m2) on the first 7 days of cycle 1, followed by oral azacitidine daily (120 to 600 mg) on the first 7 days of each additional 28-day cycle. Pharmacokinetic and pharmacodynamic profiles were evaluated during cycles 1 and 2. Adverse events and hematologic responses were recorded. Cross-over to SC azacitidine was permitted for nonresponders who received ≥ 6 cycles of oral azacitidine.

Results

Overall, 41 patients received SC and oral azacitidine (MDSs, n = 29; CMML, n = 4; AML, n = 8). Dose-limiting toxicity (grade 3/4 diarrhea) occurred at the 600-mg dose and MTD was 480 mg. Most common grade 3/4 adverse events were diarrhea (12.2%), nausea (7.3%), vomiting (7.3%), febrile neutropenia (19.5%), and fatigue (9.8%). Azacitidine exposure increased with escalating oral doses. Mean relative oral bioavailability ranged from 6.3% to 20%. Oral and SC azacitidine decreased DNA methylation in blood, with maximum effect at day 15 of each cycle. Hematologic responses occurred in patients with MDSs and CMML. Overall response rate (ie, complete remission, hematologic improvement, or RBC or platelet transfusion independence) was 35% in previously treated patients and 73% in previously untreated patients.

Conclusion

Oral azacitidine was bioavailable and demonstrated biologic and clinical activity in patients with MDSs and CMML.
Reading Bradley After Reading Laforgue: How Eliot Transformed Symbolist Poetics into a Paradigmatic Modernism
Authors: Altieri Charles
Published: May 2011

This essay asks how T. S. Eliot's dissertation work on F. H. Bradley influenced changes in his poetry: negatively from the self-consciousness attitudinizing of Laforguian analysis and positively to what a Bradleyan sense of “degrees of reality” might be said to sponsor. Bradley assumed the power he did in Eliot's thinking because he addressed many of the concerns Eliot had begun to develop from symbolist poetics, particularly its critiques of empiricism and its engagement in the infinite ironies involving the status of subjectivity. Bradley also transformed these concerns by constructing the isolated subject so that its associations with the social order become manifest. Because Eliot could show through Bradley that the world of relations is the actual substance that one lives for, he could derive concepts of humility and faith that had no place in his earlier poetics. The essay's test case is a reading of how The Waste Land fleshes out the potential in emphasizing the power of relations over the power of foundational thinking.
Bone reaction to a biomimetic third-generation hydroxyapatite coating and new surface treatment for the Symax hip stem
Authors: ten Broeke R. H. M. , Alves A. , Baumann A. , Arts J. J. C. , Geesink R. G. T.
Published: May 2011

Four uncemented Symax hip stems were extracted at three weeks and nine, 13 and 32 months, respectively, for reasons other than loosening. The reasons for implant removal were infection in two cases, recurrent dislocation in one and acetabular fracture in one. They were analysed to assess the effect and behaviour of an electrochemically deposited, completely resorbable biomimetic BONIT-hydroxyapatite (HA) coating (proximal part) and a DOTIZE surface treatment (distal part) using qualitative histology, quantitative histomorphometry and scanning electron microscopy (SEM). Early and direct bone-implant bonding with signs of active remodelling of bone and the HA coating were demonstrated by histology and SEM. No loose BONIT-HA particles or delamination of the coating were observed, and there was no inflammation or fibrous interposition at the interface.

Histomorphometry showed bone-implant contact varying between 26.5% at three weeks and 83.5% at 13 months at the HA-coated implant surface. The bone density in the area of investigation was between 24.6% at three weeks and 41.1% at 32 months. The DOTIZE surface treatment of the distal part of the stem completely prevented tissue and bone apposition in all cases, thereby optimising proximal stress transfer.

The overall features of this implant, in terms of geometry and surface texture, suggest a mechanically stable design with a highly active biomimetic coating, resulting in rapid and extensive osseo-integration, exclusively in the metaphyseal part of the stem. Early remodelling of the HA coating does not seem to have a detrimental effect on short-term bone-implant coupling. There were no adverse effects identified from either the BONIT-HA coating or the DOTIZE surface treatment.