bluuebunny/crossref_metadata_2025 huggingface dataset:
Venous Thromboembolism Risk and Thromboprophylaxis Among Hospitalized Patients
Authors: Ongen G , Yılmaz A , Cirak AK , Ersoy CY , Erden F , Altıntaş F , Yıldırım C , Güven H , Demir A , Kaynar L , Bastacı N , Demirtaş N
Published: September 2010

Objectives: To evaluate venous thromboembolism (VTE) risk and use of thromboprophylaxis in the acute care hospital setting. Methods: A total of 1701 patients hospitalized for acute or exacerbated chronic medical illnesses or elective major surgery at 11 different hospitals across Turkey were included in the study. Patients at risk and VTE prophylaxis application were retrospectively identified based on medical charts. Results: According to the American College of Chest Physicians (ACCP) criteria, overall 35.6% (606 of 1701) of the patients were identified to be at VTE risk. Venous thromboembolism-risk was observed in 64.9% of surgical and 23.8% of medical patients, the latter being lower than global Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) study results; while prophylaxis was prescribed in 39.0% and 38.5% of them, respectively. Contraindication to anticoagulant prophylaxis was observed in 8.7% of medical and 8.8% of surgical patients. Conclusions: VTE remains a risk factor among patients hospitalized across Turkey, since identification as well as prophylaxis of patients at VTE risk seems to be neglected.
Asymmetric syntactic and thematic reconfigurations in English speakers’ L2 Chinese resultative compound constructions
Authors: Boping Yuan  , Yang Zhao
Published: September 2010

This article reports on an empirical study investigating whether English speakers are able to reconstruct resultative compound structures in their second language (L2) grammars of Chinese. Results of an acceptability judgment test suggest that there are asymmetric developments in the syntactic and thematic structures of learners’ L2 Chinese resultative compounds. Syntactically, learners at intermediate and advanced stages behave native-like by allowing an activity predicate to select directly a result predicate, with the fusion of the two appearing to the left of the object, leading to the correct Chinese word order. However, they find it difficult to discard the L1-based thematic structures in their L2 Chinese. The asymmetric developments found in learners’ L2 Chinese resultative structures point to the necessity of making distinctions between syntactic and thematic developments in the study of L2 grammars.
Surrogate measurements for identifying newborns with low birth weight in a community with predominant non-hospital births
Authors: Olusanya Bolajoko O
Published: September 2010

This cross-sectional study explored the predictive utility of head circumference (HC) and crown—heel length (CHL) as surrogates for identifying birth weight < 2500g (LBW) and < 2000g (VLBW) in an inner-city community with predominant non-hospital births in Lagos, Nigeria. The accuracy of HC and CHL in detecting LBW infants was examined with discriminant analyses and receiver operating characteristic (ROC) curves. Of the 3869 singletons enrolled, 418 (10.8%) weighed < 2500g, 131 (3.4%) weighed < 2000g and 22 (0.6%) weighed < 1500g. Both predictors accurately classified 85.6 percent LBW and 91.9 percent VLBW. The optimum cut-off values for HC and CHL were 32.95cm and 45.95cm for LBW and 31.25cm and 44.85cm for VLBW respectively. HC was consistently more discriminatory than CHL for identifying both categories of LBW. In summary, HC and CHL showed satisfactory discrimination ability to detect LBW/VLBW infants and are potentially valuable as surrogates where birth weights cannot be obtained.
Building multi‐layered resilience in a malaria control programme in Dar es Salaam, Tanzania
Authors: Dongus Stefan , Pfeiffer Constanze , Metta Emmy , Mbuyita Selemani , Obrist Brigit
Published: September 2010

This study applied the multi‐layered social resilience framework in the context of an urban malaria control programme by using a qualitative approach. It was found that exchange between and within administrative levels supported resilience‐building processes in terms of mosquito breeding site elimination. ‘Reactive’ and ‘proactive’ capacities were successfully built among programme staff. However, more potential could be tapped among local leaders and household members, by increasing their competence in eliminating breeding sites of malaria vectors. Improving the communication skills of the programme’s field workers might support such processes. Together with local leaders, they could act as multipliers of sensitisation messages.
Livelihood, malaria and resilience
Authors: Obrist Brigit , Mayumana Iddy , Kessy Flora
Published: September 2010

In various parts of Sub‐Saharan Africa, malaria is endemic in areas where rain‐fed agriculture implies seasonal mobility from villages to paddy fields. Contributing to the small but growing literature on livelihood and malaria, this article examines the ways in which social actors mobilise, combine and transform capitals on the household and community levels to obtain malaria treatment. It emphasises the structuring force of cultural capital and argues that farmers of the Kilombero Valley in Tanzania develop a remarkable resilience to malaria. However, in spite of all their efforts, the web of resilience they are able to create remains rather weak and should be strengthened through intersectoral collaboration between government and civil society organisations and innovative interventions.
Adult protection: The processes and outcomes of adult protection referrals in two English local authorities
Authors: Cambridge Paul , Beadle-Brown Julie , Milne Alisoun , Mansell Jim , Whelton Beckie
Published: September 2010

• Summary: This article examines the processes and outcomes of adult protection referrals in two local authorities in England using adult protection monitoring data collected between 1998 and 2005, identifying learning for the use and development of adult protection monitoring.

• Findings: Associations were found between aspects of process and outcome in adult protection case management; police and regulatory agency involvement increased over time, over four-fifths of referrals resulted in investigations which were associated with higher levels of inter-agency involvement, abuse was confirmed for over two-fifths of referrals, there was significant territorial variation across a range of process and outcome measures and specialist adult protection coordinators were associated with higher levels of monitoring and post-abuse work. The study concluded that more work is needed to improve and standardize adult protection monitoring data if it is to more effectively inform case management and inter-authority comparisons.

• Applications: The evidence from the study suggests that adult protection monitoring data can be used to help review and organize adult protection work at agency, team and case levels and is consequently of potential value to team managers, social workers and specialist co-ordinators working in adult protection.
International education in a national context: Introducing the International Baccalaureate Middle Years Programme in Dutch public schools
Authors: Visser Alderik
Published: September 2010

Some bilingual secondary schools in the Netherlands have introduced or are introducing the International Baccalaureate (IB) Middle Years Programme (MYP).The implementation of this international scheme at (semi-) public national Dutch schools proves anything but unproblematic. Based on a series of questionnaires filled out by school managers and MYP coordinators at other national schools offering IB programmes worldwide, the author has tried to gain insight into some of the conditions under which international education could become a success in (Dutch) national schools.
Exploring adolescents’ thinking about globalization in an international education program
Authors: Myers John P.
Published: September 2010

This research examined US high school students’ thinking about economic and cultural globalization during their participation in an international education program. The findings mapped the students’ categories for the two aspects of globalization and showed that the students’ positions were shaped by relatively stable narratives characterizing the phenomenon. In general, the ethnic minority students were found to have more critical perspectives. Suggestions based on the findings for improving the teaching of globalization in international education programs are described.
The Effects of Differential Interviewer Incentives on a Field Data Collection Effort
Authors: Rosen Jeffrey , Murphy Joe , Peytchev Andy , Riley Sarah , Lindblad Mark
Published: September 2010

Surveys routinely offer incentives to motivate respondents and increase the likelihood of their participation, yet surprisingly little is known about the effectiveness of interviewer incentives. If interviewer incentives increase interviewers’ success in gaining cooperation, they could help address declining survey response rates. In this article, we present the results of an experiment testing the effectiveness of interviewer incentives in the form of cash bonuses for each successfully completed field interview. We did not find evidence that higher payments to interviewers for each completion led to increased effort on the part of interviewers nor did they lead to higher levels of success in securing respondent cooperation. These findings suggest that per complete interviewer incentives may not be cost effective in reducing survey nonresponse.
Legislating Versus Campaigning: The Legislative Behavior of Higher Office-Seekers
Authors: Nicoll Victor Jennifer
Published: September 2010

How does a campaign for higher office affect legislators’ behavior on the floor of the House? I argue that legislators with progressive ambition have incentives to demonstrate policy specialization; however, these incentives are mitigated when ambitious legislators campaign for higher office. I develop a measure of policy specialization from floor speeches and test hypotheses with data from the careers of five classes of representatives in the U.S. House. Results show that higher office-seekers demonstrate greater specialization, except when they run for higher office.
64-Slice MDCT Angiography of Upper Extremity in Assessment of Native Hemodialysis Access
Authors: Wasinrat Jitladda , Siriapisith Thanongchai , Thamtorawat Somrach , Tongdee Trongtum
Published: September 2010

Objective: To compare multidetector row computed tomographic (MDCT) angiography with conventional digital subtraction angiography (DSA) in the evaluation of vascular access stenoses in hemodialysis patients. Materials and methods: Twenty-one consecutive patients were imaged with MDCT angiography and subsequent DSA. The superficial vein of leg was used as the route for intravenous administration. The vascular stenosis was assessed in not significant (<50% stenosis), moderate stenosis (50%-74% stenosis), severe stenosis (75%-99%), and total occlusion (100%). The accuracy, sensitivity, specificity, positive, and negative predictive values were calculated for significant vascular stenosis using DSA as the standard reference. Results: The sensitivity and specificity of MDCT angiography for the detection of significant hemodialysis vascular access were 100% (95% CI, 89.3%-100%) and 94.8% (95% CI, 89.1%-97.6%), respectively. The positive and negative predictive values were 84.2% (95% CI, 68.1%-93.4%) and 100% (95% CI, 95.8%-100%), respectively. The accuracy of MDCT angiography for detection of significant stenoses was 95.9% (95% CI, 91.4%-97.0%). Conclusions: MDCT angiography provides excellent correlation in vascular stenosis as compared with DSA in hemodialysis access. Complete assessment of entire vascular segments could be performing with MDCT angiography in planning before endovascular intervention or surgical correction.
Kinematic Variables Quantifying Upper-Extremity Performance After Stroke During Reaching and Drinking From a Glass
Authors: Murphy Margit Alt , Willén Carin , Sunnerhagen Katharina S.
Published: September 2010

Background. Three-dimensional kinematic analysis provides quantitative and qualitative assessment of upper-limb motion and is used as an outcome measure to evaluate impaired movement after stroke. The number of kinematic variables used, however, is diverse, and models for upper-extremity motion analysis vary. Objective. The authors aim to identify a set of clinically useful and sensitive kinematic variables to quantify upper-extremity motor control during a purposeful daily activity, that is, drinking from a glass. Methods. For this purpose, 19 participants with chronic stroke and 19 healthy controls reached for a glass of water, took a sip, and placed it back on a table in a standardized way. An optoelectronic system captured 3-dimensional kinematics. Kinematical parameters describing movement time, velocity, strategy and smoothness, interjoint coordination, and compensatory movements were analyzed between groups. Results. The majority of kinematic variables showed significant differences between study groups. The number of movement units, total movement time, and peak angular velocity of elbow discriminated best between healthy participants and those with stroke as well as between those with moderate (Fugl-Meyer scores of 39-57) versus mild (Fugl-Meyer scores of 58-64) arm impairment. In addition, the measures of compensatory trunk and arm movements discriminated between those with moderate and mild stroke impairment. Conclusion. Kinematic analysis in this study identified a set of movement variables during a functional task that may serve as an objective assessment of upper-extremity motor performance in persons who can complete a task, such as reaching and drinking, after stroke.
A Novel Approach to Ambulatory Monitoring
Authors: Prajapati Sanjay K. , Gage William H. , Brooks Dina , Black Sandra E. , McIlroy William E.
Published: September 2010

Background. Promoting whole body activities, such as walking, can help improve recovery after stroke. However, little information exists regarding the characteristics of daily walking in patients enrolled in rehabilitation poststroke. The objectives of this study were to: (1) examine the quantity of walking and duration of individual bouts of walking during an inpatient day, (2) compare standard laboratory symmetry measures with measures of symmetry captured throughout the day, and (3) investigate the association between quantity of walking and indices of stroke severity. Methods. The study examined ambulatory activity among 16 inpatients with subacute stroke who were bilaterally instrumented with a wireless accelerometer above the ankle for approximately 8 continuous hours. Results. On average, patients demonstrated 47.5 minutes (standard deviation [SD] = 26.6 minutes) of total walking activity and walking bout durations of 54.4 s (SD = 21.5 s). A statistically significant association was found between the number of walking bouts to total walking time ( r = .76; P = .006) and laboratory gait speed ( r = .51; P = .045) and between laboratory gait speed and balance impairment ( r = .60; P = .013). Also, a significant increase in gait asymmetry was observed during day-long measurement compared with the standard laboratory-based assessment ( P = .006). Conclusions. Rather modest amounts of daily walking were found for these ambulatory inpatients, consistent with previous reports about patients after stroke. Bouts of walking were short in duration, and the gait was more asymmetrical, compared with a standard gait assessment. Unobtrusive monitoring of daily walking exposes the characteristics and temporal qualities of poststroke ambulation.
Maximal killing of lymphoma cells by DNA damage–inducing therapy requires not only the p53 targets Puma and Noxa, but also Bim
Authors: Happo Lina , Cragg Mark S. , Phipson Belinda , Haga Jon M. , Jansen Elisa S. , Herold Marco J. , Dewson Grant , Michalak Ewa M. , Vandenberg Cassandra J. , Smyth Gordon K. , Strasser Andreas , Cory Suzanne , Scott Clare L.
Published: September 2010

DNA-damaging chemotherapy is the backbone of cancer treatment, although it is not clear how such treatments kill tumor cells. In nontransformed lymphoid cells, the combined loss of 2 proapoptotic p53 target genes, Puma and Noxa, induces as much resistance to DNA damage as loss of p53 itself. In Eμ-Myc lymphomas, however, lack of both Puma and Noxa resulted in no greater drug resistance than lack of Puma alone. A third B-cell lymphoma-2 homology domain (BH)3-only gene, Bim, although not a direct p53 target, was up-regulated in Eμ-Myc lymphomas incurring DNA damage, and knockdown of Bim levels markedly increased the drug resistance of Eμ-Myc/Puma−/−Noxa−/− lymphomas both in vitro and in vivo. Remarkably, c-MYC–driven lymphoma cell lines from Noxa−/−Puma−/−Bim−/− mice were as resistant as those lacking p53. Thus, the combinatorial action of Puma, Noxa, and Bim is critical for optimal apoptotic responses of lymphoma cells to 2 commonly used DNA-damaging chemotherapeutic agents, identifying Bim as an additional biomarker for treatment outcome in the clinic.
Notch/Delta4 signaling inhibits human megakaryocytic terminal differentiation
Authors: Poirault-Chassac Sonia , Six Emmanuelle , Catelain Cyril , Lavergne Mélanie , Villeval Jean-Luc , Vainchenker William , Lauret Evelyne
Published: September 2010

The effects of Notch signaling on human megakaryocytic and erythroid differentiation were investigated by exposing human CD34+ progenitor cells to an immobilized chimeric form of the Notch ligand, Delta-like4 (Dll4Fc). Exposure of human cord blood CD34+ cells to Dll4Fc induced a modest enhancement of erythroid cell production. Conversely, under megakaryocytic culture conditions, Dll4Fc strongly impaired platelet production by reducing the generation of mature CD41a+CD42b+ megakaryocytes (MKs) and platelet-forming cells. The inhibitory activity of Dll4 on terminal MK differentiation was confirmed by culturing CD34+ cells onto Dll-4–expressing stroma cells (engineered to express the membrane-anchored form of Dll4). The reduced production of mature CD41a+CD42+ cells was rescued by inhibiting Notch signaling either with the N-N-(3,5-difluorophenacetyl-L-alanyl)-S-phenylglycine t-butyl ester γ-secretase inhibitor or the dominant-negative version of Mastermind. Dll4 impaired the generation of mature CD41a+CD42b+ cells and proplatelet formation without affecting earlier steps of MK differentiation, such as production of megakaryocytic/erythroid progenitors and colony-forming units–MKs. This blockade was accompanied by a modulation of the transcriptional program of megakaryocytic differentiation. All these results indicate that Dll4/Notch signaling inhibits human terminal MK differentiation.
Tumor vaccine composed of C-class CpG oligodeoxynucleotides and irradiated tumor cells induces long-term antitumor immunity
Authors: Cerkovnik Petra , Novakovic Barbara Jezersek , Stegel Vida , Novakovic Srdjan
Published: September 2010

Background

An ideal tumor vaccine should activate both effector and memory immune response against tumor-specific antigens. Beside the CD8+ T cells that play a central role in the generation of a protective immune response and of long-term memory, dendritic cells (DCs) are important for the induction, coordination and regulation of the adaptive immune response. The DCs can conduct all of the elements of the immune orchestra and are therefore a fundamental target and tool for vaccination. The present study was aimed at assessing the ability of tumor vaccine composed of C-class CpG ODNs and irradiated melanoma tumor cells B16F1 followed by two additional injections of CpG ODNs to induce the generation of a functional long-term memory response in experimental tumor model in mice (i.p. B16F1).

Results

It has been shown that the functional memory response in vaccinated mice persists for at least 60 days after the last vaccination. Repeated vaccination also improves the survival of experimental animals compared to single vaccination, whereas the proportion of animals totally protected from the development of aggressive i.p. B16F1 tumors after vaccination repeated three times varies between 88.9%-100.0%. Additionally, the long-term immune memory and tumor protection is maintained over a prolonged period of time of at least 8 months. Finally, it has been demonstrated that following the vaccination the tumor-specific memory cells predominantly reside in bone marrow and peritoneal tissue and are in a more active state than their splenic counterparts.

Conclusions

In this study we demonstrated that tumor vaccine composed of C-class CpG ODNs and irradiated tumor cells followed by two additional injections of CpG ODNs induces a long-term immunity against aggressive B16F1 tumors.
Adenoviral delivery of pan-caspase inhibitor p35 enhances bystander killing by P450 gene-directed enzyme prodrug therapy using cyclophosphamide+
Authors: Doloff Joshua C , Su Ting , Waxman David J
Published: September 2010

Background

Cytochrome P450-based suicide gene therapy for cancer using prodrugs such as cyclophosphamide (CPA) increases anti-tumor activity, both directly and via a bystander killing mechanism. Bystander cell killing is essential for the clinical success of this treatment strategy, given the difficulty of achieving 100% efficient gene delivery in vivo using current technologies. Previous studies have shown that the pan-caspase inhibitor p35 significantly increases CPA-induced bystander killing by tumor cells that stably express P450 enzyme CYP2B6 (Schwartz et al, (2002) Cancer Res. 62: 6928-37).

Methods

To further develop this approach, we constructed and characterized a replication-defective adenovirus, Adeno-2B6/p35, which expresses p35 in combination with CYP2B6 and its electron transfer partner, P450 reductase.

Results

The expression of p35 in Adeno-2B6/p35-infected tumor cells inhibited caspase activation, delaying the death of the CYP2B6 "factory" cells that produce active CPA metabolites, and increased bystander tumor cell killing compared to that achieved in the absence of p35. Tumor cells infected with Adeno-2B6/p35 were readily killed by cisplatin and doxorubicin, indicating that p35 expression is not associated with acquisition of general drug resistance. Finally, p35 did not inhibit viral release when the replication-competent adenovirus ONYX-017 was used as a helper virus to facilitate co-replication and spread of Adeno-2B6/p35 and further increase CPA-induced bystander cell killing.

Conclusions

The introduction of p35 into gene therapeutic regimens constitutes an effective approach to increase bystander killing by cytochrome P450 gene therapy. This strategy may also be used to enhance other bystander cytotoxic therapies, including those involving the production of tumor cell toxic protein products.
Epidemiologic surveillance of nosocomial infections in a Pediatric Intensive Care Unit of a developing country
Authors: Becerra María R , Tantaleán José A , Suárez Víctor J , Alvarado Margarita C , Candela Jorge L , Urcia Flor C
Published: September 2010

Background

Nosocomial Infections (NI) are a frequent and relevant problem. The purpose of this study was to determine the epidemiology of the three most common NI in a Pediatric Intensive Care Unit from a developing country.

Methods

We performed a prospective study in a single Pediatric Intensive Care Unit during 12 months. Children were assessed for 3 NI: bloodstream infections (BSI), ventilator-associated pneumonia (VAP) and urinary tract infections (UTI), according to Center for Disease Control criteria. Use of devices (endotracheal tube [ETT], central venous catheter [CVC] and urinary catheter [UC]) was recorded.

Results

Four hundred fourteen patients were admitted; 81 patients (19.5%) developed 85 NIs. Density of incidence of BSI, VAP and UTI was 18.1, 7.9 and 5.1/1000 days of use of CVC, ETT and UC respectively. BSI was more common in children with CVCs than in those without CVCs (20% vs. 4.7%, p < 0.05). Candida spp. was the commonest microorganism in BSI (41%), followed by Coagulase-negative Staphylococcus (17%). Pseudomonas (52%) was the most common germ for VAP and Candida (71%) for UTI. The presence of NI was associated with increased mortality (38.2% vs. 20.4% in children without NI; p < 0.001) and the median length of ICU stay (23 vs. 6 days in children without NI; p < 0.001). Children with NI had longer average hospital stay previous to diagnosis of this condition (12.3 vs. 6 days; p < 0.001).

Conclusions

One of every 5 children acquires an NI in the PICU. Its presence was associated with increased mortality and length of stay. At the same time a longer stay was associated with an increased risk of developing NI.
Design of splints based on the NiTi alloy for the correction of joint deformities in the fingers
Authors: Puértolas Sergio , Pérez-García José M , Gracia Luis , Cegoñino José , Ibarz Elena , Puértolas José A , Herrera Antonio
Published: September 2010

Background

The proximal interphalange joint (PIP) is fundamental for the functional nature of the hand. The contracture in flexion of the PIP, secondary to traumatisms or illnesses leads to an important functional loss. The use of correcting splints is the common procedure for treating this problem. Its functioning is based on the application of a small load and a prolonged stress which can be dynamic, static progressive or static serial.

It is important that the therapist has a splint available which can release a constant and sufficient force to correct the contracture in flexion. Nowadays NiTi is commonly used in bio-engineering, due to its superelastical characteristics. The experience of the authors in the design of other devices based on the NiTi alloy, makes it possible to carry out a new design in this work - the production of a finger splint for the treatment of the contracture in flexion of the PIP joint.

Methods

Commercial orthosis have been characterized using a universal INSTRON 5565 machine. A computational simulation of the proposed design has been conducted, reproducing its performance and using a model "ad hoc" for the NiTi material. Once the parameters have been adjusted, the design is validated using the same type of test as those carried out on commercial orthosis.

Results and Discussion

For commercial splint the recovering force falls to excessively low values as the angle increases. Angle curves for different lengths and thicknesses of the proposed design have been obtained, with a practically constant recovering force value over a wide range of angles that vary between 30° and 150° in every case. Then the whole treatment is possible with only one splint, and without the need of progressive replacements as the joint recovers.

Conclusions

A new model of splint based on NiTi alloy has been designed, simulated and tested comparing its behaviour with two of the most regularly used splints. Its uses is recommended instead of other dynamic orthosis used in orthopaedics for the PIP joint. Besides, its extremely simple design, makes its manufacture and use on the part of the specialist easier.
Periodic pattern detection in sparse boolean sequences
Authors: Junier Ivan , Hérisson Joan , Képès François
Published: September 2010

Background

The specific position of functionally related genes along the DNA has been shown to reflect the interplay between chromosome structure and genetic regulation. By investigating the statistical properties of the distances separating such genes, several studies have highlighted various periodic trends. In many cases, however, groups built up from co-functional or co-regulated genes are small and contain wrong information (data contamination) so that the statistics is poorly exploitable. In addition, gene positions are not expected to satisfy a perfectly ordered pattern along the DNA. Within this scope, we present an algorithm that aims to highlight periodic patterns in sparse boolean sequences, i.e. sequences of the type 010011011010... where the ratio of the number of 1's (denoting here the transcription start of a gene) to 0's is small.

Results

The algorithm is particularly robust with respect to strong signal distortions such as the addition of 1's at arbitrary positions (contaminated data), the deletion of existing 1's in the sequence (missing data) and the presence of disorder in the position of the 1's (noise). This robustness property stems from an appropriate exploitation of the remarkable alignment properties of periodic points in solenoidal coordinates.

Conclusions

The efficiency of the algorithm is demonstrated in situations where standard Fourier-based spectral methods are poorly adapted. We also show how the proposed framework allows to identify the 1's that participate in the periodic trends, i.e. how the framework allows to allocate a positional score to genes, in the same spirit of the sequence score. The software is available for public use at http://www.issb.genopole.fr/MEGA/Softwares/iSSB_SolenoidalApplication.zip.
Prediction of quantitative phenotypes based on genetic networks: a case study in yeast sporulation
Authors: Shen Li , Chepelev Iouri , Liu Jie , Wang Wei
Published: September 2010

Background

An exciting application of genetic network is to predict phenotypic consequences for environmental cues or genetic perturbations. However, de novo prediction for quantitative phenotypes based on network topology is always a challenging task.

Results

Using yeast sporulation as a model system, we have assembled a genetic network from literature and exploited Boolean network to predict sporulation efficiency change upon deleting individual genes. We observe that predictions based on the curated network correlate well with the experimentally measured values. In addition, computational analysis reveals the robustness and hysteresis of the yeast sporulation network and uncovers several patterns of sporulation efficiency change caused by double gene deletion. These discoveries may guide future investigation of underlying mechanisms. We have also shown that a hybridized genetic network reconstructed from both temporal microarray data and literature is able to achieve a satisfactory prediction accuracy of the same quantitative phenotypes.

Conclusions

This case study illustrates the value of predicting quantitative phenotypes based on genetic network and provides a generic approach.
Augmented inhibition of angiogenesis by combination of HER2 antibody chA21 and trastuzumab in human ovarian carcinoma xenograft
Authors: Zhang Anli , Shen Guodong , Zhao Ting , Zhang Guihong , Liu Jing , Song Lihua , Wei Wei , Bing Ling , Wu Zhengsheng , Wu Qiang
Published: September 2010

Background

chA21 is a novel tumor-inhibitory antibody which recognized subdomain I of HER2 extracellular domain with an epitope distinct from other HER2 antibodies. Previously, we demonstrated that chA21 inhibits human ovarian carcinoma cell line SKOV-3 growth in vitro and in vivo study. In this study, we further investigated the anti-angiogenic efficacy combination of chA21 with trastuzumab in SKOV-3 xenograft model.

Methods

Nude mice were s.c. challenged with SKOV-3 cells and received treatment of chA21 alone, trastuzumab alone or both antibodies together twice a week for 21 days. Tumor volume and microvessel density (MVD) were evaluated. The effect of chA21 plus trastuzumab treament on vascular endothelial growth factor (VEGF) secretion, endothelial cells proliferation and migration, and the status of HER2 downstream pathway AKT/phosphorylated AKT (pAKT) were evaluated in vitro.

Results

In vivo study combination of chA21 with trastuzumab resulted in reduce tumor growth and angiogenesis than each monotherapy. In vitro study, the combination of chA21 with trastuzumab inhibits VEGF secretion, endothelial cells proliferation and migration. Furthermore, the combination treatment inhibits pAKT expression.

Conclusion

Our findings suggested that the combination of chA21 with trastuzumab can cause augmented inhibition of angiogenesis in SKOV-3 xenograft model. Inhibition of agniogenesis may through suppression of AKT pathway. The therapeutic benefits of combination chA21 with trastuzumab warrant further study in an attempt to make the translation into the clinic.
The Belgian MIRA (MabThera In Rheumatoid Arthritis) registry: clues for the optimization of rituximab treatment strategies
Authors: Vander Cruyssen Bert , Durez Patrick , Westhovens Rene , Kaiser Marie-Joelle , Hoffman Ilse , De Keyser Filip ,   The MIRA Study Group
Published: September 2010

Introduction

This study describes the results of the Belgian 'MabThera In Rheumatoid Arthritis (MIRA)' registry: effectiveness, safety and evaluation of the current retreatment practice on the background of the Belgian reimbursement criteria for rituximab.

Methods

All Belgian rheumatologists had the possibility to participate in the study. Patients entered the registry in November 2006 and the entry is still open.

Results

By mid-September 2009, 401 patients had entered the registry with a mean follow-up time of 70 weeks. Overall, DAS28-ESR decreased from 6.0 at baseline to 4.2 at week 16. Further decrease of disease activity was observed at the end of year 1 and year 2 with mean DAS28-ESR of 4.0 and 3.7 at these respective time points. More than 80% of patients showed a EULAR response at week 16. Patients could be retreated if they had DAS scores of > 3.2 at least 6 months after the previous course. Second and third courses were given in 224 and 104 patients, respectively. At month 6 after the second course, significantly lower DAS28-ESR values were observed compared to the first course. This was especially the case for patients who were retreated before they showed an obvious flare (DAS increase > 1.2).

Conclusions

This study describes the follow-up of a daily clinical practice cohort of 401 RA patients with long-standing refractory disease treated with rituximab. Relatively high DAS28 values at the start of each retreatment, compared to values 6 months after each treatment course, were noted. Moreover, further decrease of DAS28 scores after the second course was significantly more pronounced in those patients who didn't show an obvious flare. These two elements suggest that treatment of RA patients with rituximab could be optimized by earlier retreatment.
Breast tumor kinase and extracellular signal-regulated kinase 5 mediate Met receptor signaling to cell migration in breast cancer cells
Authors: Castro Nancy E , Lange Carol A
Published: September 2010

Introduction

Breast tumor kinase (Brk/protein tyrosine kinase 6 (PTK6)) is a nonreceptor, soluble tyrosine kinase overexpressed in the majority of breast tumors. Previous work has placed Brk downstream of epidermal growth factor receptor (ErbB) activation and upstream of extracellular signal-regulated kinase 5 (ERK5) and p38 mitogen-activated protein (MAP) kinases. Herein we investigate the regulation of Brk kinase activity and cell migration in response to treatment of keratinocytes (HaCaT cells) and breast cancer cell lines (MDA-MB-231 and T47D cells) with hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP), peptide ligands for Met and Ron receptors, respectively.

Methods

In vitro kinase assays were performed to directly measure Brk kinase activity in response to MET and RON ligands. Transfection of Brk-targeted RNAi was used to knock down endogenous Brk or ERK5 in multiple cell lines. Kinase activities (downstream of MET signaling) were assayed by Western blotting using total and phospho-specific antibodies. Boyden chamber assays were used to measure cell migration in response to manipulation of Brk and downstream MET effectors. Rescue experiments were performed by knock down of endogenous Brk using RNAi (targeting the untranslated region (3′-UTR)) and transient transfection (re-expression) of either wild-type or kinase-inactive Brk.

Results

Brk gene silencing revealed that HGF, but not MSP, induced robust Brk-dependent cell migration. Brk and ERK5 copurified in HGF-induced protein complexes, and Brk/ERK5 complexes formed independently of Brk kinase activity. ERK5 was required for breast cancer cell but not keratinocyte cell migration, which became ERK1/2-dependent upon ERK5 knockdown. Notably, rescue experiments indicated that the kinase activity of Brk was not required for HGF-induced cell migration. Further, expression of either wild-type or kinase-inactive Brk in Brk-null MDA-MB-435 cells activated ERK5 and conferred increased HGF-induced cell migration.

Conclusions

These results have identified Brk and ERK5 as important downstream effectors of Met signaling to cell migration. Targeting ERK5 kinase activity or inhibiting the formation of Brk/ERK5 complexes may provide an additional means of blocking cell migration associated with breast cancer progression to metastasis.
Moveout analysis of wave-equation extended images
Authors: Yang Tongning , Sava Paul
Published: September 2010

Conventional velocity analysis applied to images produced by wave-equation migration with a crosscorrelation imaging condition uses moveout information from space lags or focusing information from time lag. However, more robust velocity-estimation methods can be designed to simultaneously take advantage of the semblance and focusing information provided by migrated images. Such a velocity estimation requires characterization of the moveout surfaces defined jointly for space- and time-lags extended images. The analytic solutions to the moveout surfaces can be derived by solving the system of equations representing the shifted source and receiver wavefields. The superposition of the surfaces from many experiments (shots) is equivalent to the envelope for the family of the individual surface. The envelopeforms a shape that can be characterized as a cone in the extended space of depth, space lag, and time lag. When imaged with the correct velocity, the apex of the cone is located at the correct reflection depth and at zero space and time lags. When imaged with the incorrect velocity, the apex of the cone shifts in the depth direction and along the time-lag axis. The characteristics of the cones are directly related to the quality of the velocity model. Thus, their analysis provides a rich source of information for velocity model-building. Synthetic examples verify the derived formulas characterizing the moveout surfaces. The analytic formulas match the numeric experiments well, demonstrating the accuracy of the formulas. Based on information provided by the extended imaging condition, future application for velocity updates can benefit from the robustness of the depth-focusing analysis and of the high resolution of the semblance analysis.
The Inositol Phosphatase SHIP2 Negatively Regulates Insulin/IGF-I Actions Implicated in Neuroprotection and Memory Function in Mouse Brain
Authors: Soeda Yoshiyuki , Tsuneki Hiroshi , Muranaka Hayato , Mori Norihiko , Hosoh Shuji , Ichihara Yoshinori , Kagawa Syota , Wang Xu , Toyooka Naoki , Takamura Yusaku , Uwano Teruko , Nishijo Hisao , Wada Tsutomu , Sasaoka Toshiyasu
Published: September 2010

Impairment of insulin and IGF-I signaling in the brain is one of the causes of dementia associated with diabetes mellitus and Alzheimer’s disease. However, the precise pathological processes are largely unknown. In the present study, we found that SH2-containing inositol 5′-phosphatase 2 (SHIP2), a negative regulator of phosphatidylinositol 3,4,5-trisphosphate-mediated signals, is widely expressed in adult mouse brain. When a dominant-negative mutant of SHIP2 was expressed in cultured neurons, insulin signaling was augmented, indicating physiological significance of endogenous SHIP2 in neurons. Interestingly, SHIP2 mRNA and protein expression levels were significantly increased in the brain of type 2 diabetic db/db mice. To investigate the impact of increased expression of SHIP2 in the brain, we further employed transgenic mice overexpressing SHIP2 and found that increased amounts of SHIP2 induced the disruption of insulin/IGF-I signaling through Akt. Neuroprotective effects of insulin and IGF-I were significantly attenuated in cultured cerebellar granule neurons from SHIP2 transgenic mice. Consistently, terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay demonstrated that the number of apoptosis-positive cells was increased in cerebral cortex of the transgenic mice at an elderly age. Furthermore, SHIP2 transgenic mice exhibited impaired memory performance in the Morris water maze, step-through passive avoidance, and novel-object-recognition tests. Importantly, inhibition of SHIP2 ameliorated the impairment of hippocampal synaptic plasticity and memory formation in db/db mice. These results suggest that SHIP2 is a potent negative regulator of insulin/IGF-I actions in the brain, and excess amounts of SHIP2 may be related, at least in part, to brain dysfunction in insulin resistance with type 2 diabetes.
Embodied Eloquence, the Sumner Assault, and the Transatlantic Cable
Authors: Hanlon Christopher
Published: September 2010

Hanlon's essay depicts South Carolina Congressman Preston Brooks's 1856 assault on Massachusetts Senator Charles Sumner as a flashpoint for 1850s controversies over the laying of transatlantic telegraphic cable between the United States and England. Widely treated by both Northern and Southern commentators as a form of political discourse, Brooks's caning of Sumner also reverberated with a broad set of concerns over telegraphic communication. Many noted that the cane with which Brooks assaulted Sumner was constructed of gutta-percha, the substance that was used to insulate the transatlantic cable and that served, over the course of the decade, as a metonym for advanced telecommunications technology. In Congress, Brooks's assault was depicted by Senator Andrew Butler as a rejoinder to Sumner's speech as an improper—because prepublished and internationally distributed—abolitionist diatribe. The Brooks-Sumner affair, in which a Southern legislator smote his abolitionist colleague using a fragment of the era's most salient symbol for global peace and goodwill, called forth a set of anxieties concerning the telegraphic disembodiment of the voice, the unchecked proliferation of speculation and rumor, and the globalization of the American cotton trade.
Polarization sensitivity in two species of cuttlefish –Sepia plangon(Gray 1849) andSepia mestus(Gray 1849) – demonstrated with polarized optomotor stimuli
Authors: Talbot Christopher M. , Marshall Justin
Published: September 2010

The existence of polarization sensitivity (PS), most likely resulting from the orthogonal arrangement of microvilli in photoreceptors, has been proposed in cephalopods for some time, although it has rarely been examined behaviourally. Here, we tested the mourning cuttlefish, Sepia plangon, and the reaper cuttlefish, Sepia mestus, for polarization sensitivity using a large-field optomotor stimulus containing polarization contrast. Polaroid filter drums with stripes producing alternating e-vectors were rotated around free-moving animals. Polarized optomotor responses were displayed, and these responses were similar to those performed in response to a black-and-white, vertically-striped drum, whereas no responses were displayed to a plain polarizing control drum producing just a vertical e-vector. This indicates that the animals are able to see the contrast between adjacent stripes in the polarizing drum. To our knowledge, this is the first demonstration of functional polarization sensitivity in cuttlefish.
Polarization sensitivity and retinal topography of the striped pyjama squid (Sepioloidea lineolata– Quoy/Gaimard 1832)
Authors: Talbot Christopher M. , Marshall Justin
Published: September 2010

Coleoid cephalopods (octopus, cuttlefish and squid) potentially possess polarization sensitivity (PS) based on photoreceptor structure, but this idea has rarely been tested behaviourally. Here, we use a polarized, striped optokinetic stimulus to demonstrate PS in the striped pyjama squid, Sepioloidea lineolata. This species displayed strong, consistent optokinetic nystagmic eye movements in response to a drum with stripes producing e-vectors set to 0 deg, 45 deg, 90 deg and 135 deg that would only be visible to an animal with PS. This is the first behavioural demonstration of a polarized optokinetic response in any species of cephalopod. This species, which typically sits beneath the substrate surface looking upwards for potential predators and prey, possesses a dorsally shifted horizontal pupil slit. Accordingly, it was found to possess a horizontal strip of high-density photoreceptors shifted ventrally in the retina, suggesting modifications such as a change in sensitivity or resolution to the dorsal visual field.
Modifying the Mean-Variance Approach to Avoid Violations of Stochastic Dominance
Authors: Blavatskyy Pavlo R.
Published: September 2010

The mean-variance approach is an influential theory of decision under risk proposed by Markowitz (Markowitz, H. 1952. Portfolio selection. J. Finance 7(1) 77–91). The mean-variance approach implies violations of first-order stochastic dominance not commonly observed in the data. This paper proposes a new model in the spirit of the classical mean-variance approach without violations of stochastic dominance. The proposed model represents preferences by a functional U(L) − ρ · r(L), where U(L) denotes the expected utility of lottery L, ρ ∈ [−1, 1] is a subjective constant, and r(L) is the mean absolute (utility) semideviation of lottery L. The model comprises a linear trade-off between expected utility and utility dispersion. The model can accommodate several behavioral regularities such as the Allais paradox and switching behavior in Samuelson's example.
Lactic acid is of low predictive value for the diagnosis of bacterial infection in ventricular cerebrospinal fluid samples containing residual blood
Authors: Böer Klas , Pfister Wolfgang , Kiehntopf Michael
Published: September 2010

Background: Lactic acid concentrations (LA) are an established marker of bacterial infection in cerebrospinal fluid (CSF). However, use of LA for the detection of infection in CSF with residual blood has not been fully evaluated.

Methods: Analysis of LA and total protein, cell count and bacterial culture were performed in 90 lumbar and ventricular CSF samples contaminated with blood.

Results: Bacterial culture was positive in six CSF samples. The diagnostic value of the cell count was significantly higher than that of LA for the prediction of a positive culture, even if all culture positive and all likely infected samples were included in the analysis. There was no significant difference in LA concentrations between positive or likely positive ventricular CSF samples and all negative, ventricular samples.

Conclusions: Although LA concentrations in CSF are evidently a predictor of bacterial infection, its diagnostic value for the detection of bacterial infection in ventricular CSF with residual blood is limited.

Clin Chem Lab Med 2010;48:1777–80.