bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracellular Activation of SGN-35, a Potent Anti-CD30 Antibody-Drug Conjugate
Authors: Okeley Nicole M. , Miyamoto Jamie B. , Zhang Xinqun , Sanderson Russell J. , Benjamin Dennis R. , Sievers Eric L. , Senter Peter D. , Alley Stephen C.
Published: January 2010

Purpose: SGN-35 is an antibody-drug conjugate (ADC) containing the potent antimitotic drug, monomethylauristatin E (MMAE), linked to the anti-CD30 monoclonal antibody, cAC10. As previously shown, SGN-35 treatment regresses and cures established Hodgkin lymphoma and anaplastic large cell lymphoma xenografts. Recently, the ADC has been shown to possess pronounced activity in clinical trials. Here, we investigate the molecular basis for the activities of SGN-35 by determining the extent of targeted intracellular drug release and retention, and bystander activities.

Experimental Design: SGN-35 was prepared with 14C-labeled MMAE. Intracellular ADC activation on CD30+ and negative cell lines was determined using a combination of radiometric and liquid chromatograhpy/mass spectrometry-based assays. The bystander activity of SGN-35 was determined using mixed tumor cell cultures consisting of CD30+ and CD30− lines.

Results: SGN-35 treatment of CD30+ cells leads to efficient intracellular release of chemically unmodified MMAE, with intracellular concentrations of MMAE in the range of 500 nmol/L. This was due to specific ADC binding, uptake, MMAE retention, and receptor recycling or resynthesis. MMAE accounts for the total detectable released drug from CD30+ cells, and has a half-life of retention of 15 to 20 h. Cytotoxicity studies with mixtures of CD30+ and CD30− cell lines indicated that diffusible released MMAE from CD30+ cells was able to kill cocultivated CD30− cells.

Conclusions: MMAE is efficiently released from SGN-35 within CD30+ cancer cells and, due to its membrane permeability, is able to exert cytotoxic activity on bystander cells. This provides mechanistic insight into the pronounced preclinical and clinical antitumor activities observed with SGN-35. Clin Cancer Res; 16(3); 888–97
Aggressive Chronic Lymphocytic Leukemia with Elevated Genomic Complexity Is Associated with Multiple Gene Defects in the Response to DNA Double-Strand Breaks
Authors: Ouillette Peter , Fossum Samuel , Parkin Brian , Ding Li , Bockenstedt Paula , Al-Zoubi Ammar , Shedden Kerby , Malek Sami N.
Published: January 2010

Purpose: Genomic complexity is present in approximately 15% to 30% of all chronic lymphocytic leukemia (CLL) and has emerged as a strong independent predictor of rapid disease progression and short remission duration in CLL. We conducted this study to advance our understanding of the causes of genomic complexity in CLL.

Experimental Design: We have obtained quantitative measurements of radiation-induced apoptosis and radiation-induced ATM autophosphorylation in purified CLL cells from 158 and 140 patients, respectively, and have used multivariate analysis to identify independent contributions of various biological variables on genomic complexity in CLL.

Results: Here, we identify a strong independent effect of radiation resistance on elevated genomic complexity in CLL and describe radiation resistance as a predictor for shortened CLL survival. Furthermore, using multivariate analysis, we identify del17p/p53 aberrations, del11q, del13q14 type II (invariably resulting in Rb loss), and CD38 expression as independent predictors of genomic complexity in CLL, with aberrant p53 as a predictor of ∼50% of genomic complexity in CLL. Focusing on del11q, we determined that normalized ATM activity was a modest predictor of genomic complexity but was not independent of del11q. Through single nucleotide polymorphism array–based fine mapping of del11q, we identified frequent monoallelic loss of Mre11 and H2AFX in addition to ATM, indicative of compound del11q–resident gene defects in the DNA double-strand break response.

Conclusions: Our quantitative analysis links multiple molecular defects, including for the first time del11q and large 13q14 deletions (type II), to elevated genomic complexity in CLL, thereby suggesting mechanisms for the observed clinical aggressiveness of CLL in patients with unstable genomes. Clin Cancer Res; 16(3); 835–47
Does Pretreatment with Lansoprazole Influence Helicobacter pylori Eradication Rate and Quality of Life?
Authors: Inoue Masafumi , Okada Hiroyuki , Hori Shinichiro , Kawahara Yoshiro , Kawano Seiji , Takenaka Ryuta , Toyokawa Tatsuya , Onishi Yasuhiro , Shiratori Yasushi , Yamamoto Kazuhide
Published: January 2010

Background/Aims: It is controversial whether pretreatment with a proton pump inhibitor (PPI) before Helicobacter pylori eradication treatment decreases the eradication rate. To determine the effects of pretreatment with lansoprazole alone, followed by an H. pylori eradication regimen (lansoprazole 30 mg, amoxicillin 750 mg and clarithromycin 200 mg twice daily for 1 week), on the eradication rate and quality of life (QoL) of the patient. Methods: Patients with H. pylori-positive peptic ulcer were randomly assigned to two groups. The patients received either lansoprazole (30 mg) once daily for 6–8 weeks before H. pylori eradication (group A), or eradication treatment and then lansoprazole (30 mg) for 6–8 weeks (group B). To assess the QoL of the patients, the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire was evaluated. Results: A total of 116 patients were enrolled. The cure rates were 78.9% in group A and 78.0% in group B. In both groups, GSRS analysis showed a significant improvement of the overall GSRS score at the assessment of eradication efficacy, compared to baseline; there was no difference between the groups. Conclusion: With this H. pylori eradication regimen, there was no difference in the cure rates and QoL associated with PPI pretreatment.
Harm Avoidance as a Mediator of Treatment Response to Antidepressant Treatment of Patients with Major Depression
Authors: Quilty Lena C. , Godfrey Kathryn M. , Kennedy Sidney H. , Bagby R. Michael
Published: January 2010

Background: The temperament harm avoidance (HA) has consistently demonstrated an association with major depressive disorder (MDD), serotonin functioning and reduction in depression symptoms in response to antidepressant medications targeting the serotonin system. In the current investigation, we examine HA as a potential mediator of treatment response to a serotonergic tricyclic antidepressant. Methods: Outpatients (n = 150) with MDD were randomized to receive clomipramine or a control treatment. Patients completed the Hamilton Rating Scale for Depression (Ham-D) and the Tridimensional Personality Questionnaire (TPQ) prior to treatment initiation, and then again after at least 8 weeks of treatment. Using structural equation modeling, we evaluated a ‘mediation model’ in which change in HA is a mechanism of depression change in response to clomipramine, and a ‘complication model’ in which reduction in HA is a by-product of depression change. Results: The mediation model provided a good fit to the data by all indices, whereas the complication model did not. Patients treated with clomipramine exhibited a greater decrease in HA as compared to those in the control group; moreover, HA reduction was associated with depression reduction. Conclusions: HA mediated the response to antidepressant treatment, such that any treatment effect of clomipramine occurred through HA reduction. Although replication with multiple assessment periods is required to determine if HA reduction actually precedes depression reduction, the results contribute to a growing body of literature implicating personality constructs subsumed within negative emotionality as mediators of treatment response to medications targeting serotonergic functioning.
Prevalence of Chronic Kidney Disease in a Rural Chinese Adult Population: The Handan Eye Study
Authors: Jiang LiPing , Liang YuanBo , Qiu Bo , Wang FengHua , Duan XinRong , Yang XiaoHui , Huang Wen , Wang NingLi
Published: January 2010

Background: Chronic kidney disease (CKD) is a worldwide public health problem. The purpose of this study was to investigate the prevalence of CKD and associated factors in a rural adult population in Northern China. Methods: This was a cross-sectional study using data from the Handan Eye Study. A total of 5,105 subjects aged ≧30 years were included in this analysis. Spot urine albumin-to-creatinine ratio was determined. Glomerular filtration rate was estimated with the modified Modification of Diet in Renal Disease equation. CKD was defined by the guidelines proposed by the Kidney Disease Outcomes Quality Initiative. The associations between age, gender, diabetes, hypertension, and kidney damage were examined. Results: Albuminuria and reduced renal function were detected in 16.8 and 0.4% of subjects, respectively. The age-standardized prevalence of albuminuria, reduced renal function and CKD was 14.9% (95% confidence interval (CI) 13.9–15.9), 0.38% (95% CI 0.21–0.55) and 15.2% (95% CI 14.2–16.2), respectively. The prevalence of CKD was greater in women than in men (16.7 vs. 12.9%, respectively, p < 0.001). The increased prevalence of CKD with increasing age was observed in both genders. Older age, female gender, diabetes and hypertension were independently associated with albuminuria. Older age was independently associated with reduced renal function. Conclusion: The prevalence of CKD in the rural Chinese population is relatively high. Factors associated with CKD are similar to those of urban areas in China and developed countries. CKD is a major public health problem in rural China.
The Griffoniasimplicifolia I Isolectin B4 and Tomato Lectin Recognize Astrocytes instead of Microglia in Adult Hamster Retina
Authors: Chung Kwok-hang , Cho Eric Y.P.
Published: January 2010

Two lectins, Griffonia simplicifolia I isolectin B4 (GS-I lectin) and Lycopersicon esculentum (LE) lectin, reported to be specific microglia markers in a number of animals including rodents, were used to stain hamster retinas. In the adult hamster retina, both of them failed to stain microglia but instead labeled astrocytes (in addition to endothelial cells). GS-I lectin-positive astrocytes were mainly located at peripheral regions of the retina but were variable in number and staining intensity, while LE lectin stained most astrocytes as judged by co-localization with anti-glial fibrillary acidic protein staining. To see whether astrocytes (and/or microglia) would be labeled by the lectins during postnatal retinal development, retinas from newborns all the way to adults were studied. Starting from P0, GS-I lectin selectively labeled astrocytes located adjacent to and peripheral to the tips of developing blood vessels, suggesting a functional association of glycoproteins containing α-D-galactose (the terminal sugar residue with binding affinity to GS-I) with the migration of the astrocytic front during development. The GS-I lectin staining on this population of astrocytes became reduced as the astrocytic front reached the retinal periphery, so that in the adult only astrocytes in the periphery became positive for GS-I. In contrast, LE lectin stained most astrocytes in the developing retina, starting from P2 and with maximum staining intensity achieved around P14, which continued unchanged to adulthood. During early postnatal retinal development, both lectins could label microglia, but the staining was abolished well before the retina became mature. GS-I could label microglia until P18, and the stained cells were mainly confined to the retinal periphery where blood vessels were absent, suggesting that expression of the terminal α-D-galactose residue is regulated by interaction with the developing vasculature (and/or astrocytes). LE could mark microglia till P6, but the labeling was weaker compared with GS-I. The results indicate that at least in the hamster, GS-I and LE lectin may be a more selective marker for retinal astrocytes than microglia. It would be interesting to see whether some other animals will exhibit a similar picture, and whether the expression of the sugar residues (specific for GS-I and LE lectin binding) on astrocytes instead of microglia will confer any functional consequences uniquely different from those animals with specific microglia binding.
Expression of Dab2, a Tumor Suppressor, in the Human Fetal Hippocampus and Neocortex
Authors: Chan Wood Yee , Xia Chun Lin , Yew David T. , Zhao Hui , Mok Samuel C.
Published: January 2010

Dab2, first identified as a tumor suppressor in ovarian cancerous cells and tissues, is an adaptor protein involved in several signal transduction pathways. Our previous studies of mouse embryos have shown that Dab2 is expressed in the early developing central nervous system and that knockdown of the protein expression perturbs the normal development of the neural tube. In this study, we investigated Dab2 expression in the human fetal hippocampus and temporal, sensory, visual, motor and frontal cortices from 12 to 32 weeks of gestation with a specific immunohistochemical staining method. The hippocampus showed the strongest Dab2 expression among all the brain regions examined. Within the hippocampus, Dab2 expression was first detected at 12–14 weeks in all cellular layers with varying intensities, and the highest level of expression was observed in the pyramidal layer at 26–28 weeks. In the temporal cortex, Dab2 was also expressed in all cellular layers at 12–14 weeks, and its expression peaked at 18–20 weeks and then became weaker at 26–32 weeks. The expression pattern was different in the sensory cortex: the expression was the strongest at 12–14 weeks and then gradually reduced with age. In the visual cortex, Dab2 expression was mainly localized in the marginal zone, upper cortical plate and subcortical layers, whereas the motor and frontal cortices exhibited only low levels of Dab2 expression mostly in the subcortical layers. Our results demonstrated a specific spatiotemporal pattern of Dab2 expression in the human fetal hippocampus and neocortex, implicating roles of Dab2 in the early development of the human brain.
The Sense of Belonging in New Urban Zones of Transition
Authors: Jørgensen Anja
Published: January 2010

In most modern sociological literature, it is a rarity to find analyses suggesting that social bonds and the sense of belonging can be strong in socially deprived areas. In the classic Chicago tradition of sociology, in the works of Park et al. and in Louis Wirth’s The Ghetto, residential areas are described both as places in which the social bonds are loose and places with strong bonds. However, a focal point in this article is that the sense of place and belonging are related to the type and the quality of local social bonds. The article discusses the sense of belonging in socially deprived areas by using and adapting classic concepts and insights of human ecology as formulated by the classical Chicago sociologists Robert E. Park and Ernest W. Burgess. Recent sociological contributions about belonging and the sense of place, including recent empirical studies on the topic, are also addressed. It is argued that two socially deprived neighbourhoods with identical social profiles measured by traditional sociological variables as average income, educational level, unemployment, ethnicity, welfare benefits, etc. can be very different when it comes to local community and local social networks.
Wounded by Friendly Fire
Authors: Cable Sherry , Shriver Thomas E.
Published: January 2010

Political movements seek influence in policy-making, but are typically marked by intra-movement conflict, which, analysts argue, reduces the achievement of social change. This article examines the effects of conflict within the Gulf War illness movement on its influencing government policy-making. Using in-depth interviews, participant observation and document analyses, the article assesses the movement’s policy outcome, examines the substance of the conflict and analyzes the ways in which it hampered the movement’s execution of policy-relevant tasks. It is found that intra-movement conflict over activists’ divergent views of the government’s intentionality with regard to veterans’ hazardous exposure impaired the movement’s execution of tasks that would have had a critical influence on policy-making. As a consequence, public pressure was insufficient to precipitate a legitimation crisis for the state, permitting government officials to evade the movement’s demands and liability while imparting the image of responsiveness through weak policy formulations and implementation. The outcome was one of policy palliatives rather than curatives.
Socio-psychological implications for an occupying society: The case of Israel
Authors: Halperin Eran , Bar-Tal Daniel , Sharvit Keren , Rosler Nimrod , Raviv Amiram
Published: January 2010

Although prolonged occupation of a nation is no longer a common phenomenon, where it does exist, it bears harsh implications for all parties involved. This article examines the socio-psychological implications of occupation on the occupying society, using the case of the Israeli occupation of the Palestinian territories of the West Bank and Gaza Strip since 1967 as an example. The article first delineates the concept of occupation from a socio-psychological perspective, which supplements the legal-formal aspect. The authors then propose a conceptual framework that analyzes the psychology of the occupying society. Within this framework, they describe the psychological challenges that the occupation may pose to the members of the occupying society. Next, they introduce psychological mechanisms that members of an occupying society may use in order to avoid facing these challenges. Finally, they offer a number of ideas regarding the relationship between these mechanisms and the process of ending the occupation.
The Validity of Self-reported Prevalence, Frequency, and Timing of Arrest: An Evaluation of Data Collected Using a Life Event Calendar
Authors: Morris Nancy A. , Slocum Lee Ann
Published: January 2010

Heightened scholarly interest in stability and change in criminal behavior has increased the demand for longitudinal data. One method that may enhance the quality of retrospective self-reported data, especially reports of timing, is the life event calendar (LEC). Using a sample of incarcerated women, we assess the validity of LEC measures of self-reported prevalence, frequency and timing of arrests over a three-year period.We also examine the validity of self—reported frequency and timing of arrest data by respondent and arrest characteristics. Results suggest that the LEC elicits valid data on prevalence and frequency of arrests, while self-reported timing of arrests is recalled with less accuracy. Saliency appears more relevant for the accuracy of self-reported frequency, as compared to timing, and substance use has no effect on validity. We discuss future research using the LEC, especially with regard to improving the recall of the timing and sequencing of criminal events.
Determinants of Health Risk Perception Among Low-risk-taking Tourists Traveling to Developing Countries
Authors: Jonas Aliza , Mansfeld Yoel , Paz Shlomit , Potasman Israel
Published: January 2010

This article focuses on tourists’ perception of health risk among tourists who intend to travel to developing countries. It examines the relative importance tourists assign to this risk. It unveils the factors that shape health risk perceptions and explores the relative role of each factor in shaping tourists’ perception. With a sample of 232 and a self-administered questionnaire, the study interviewed visitors at a travelers medical clinic before their trip. Using ordered logistic regression, the results show that health risk perception ranks relatively high against other types of risk perception. The study unveiled the relative contribution of the various determinants to the overall travelers’ perception of health risk. Furthermore, three groups of perception-type hierarchy were discovered, representing levels of importance and tourists’ potential behavioral control: first, difficult-to-control environmental components; second, partially behaviorally controllable by the tourist; third, fully behaviorally controlled types of health risks perceptions.
Trade and Conflict: Proximity, Country Size, and Measures
Authors: Keshk Omar M.G. , Reuveny Rafael , Pollins Brian M.
Published: January 2010

The effect of trade on military conflict is one of the most important questions in international relations. Liberals argue that trade brings peace, neo-realists and neo-Marxists reason that trade brings conflict, while classical realists contend that trade has no impact on conflict. This article investigates theoretically and empirically some of the most important issues that remain in this literature: the roles of geographical proximity, country size, the handling of the trade data, and the conceptualization of conflict. Employing a simultaneous equations model, we find that the claim that trade brings peace is not robust, but rather it is conflict that reduces trade.
Meeting the needs of family carers: an evaluation of three home-based palliative care services in Australia
Authors: Thomas Kristina , Hudson Peter , Oldham Lynn , Kelly Brian , Trauer Tom
Published: January 2010

While policy promotes comprehensive assessment of family carer needs and a plan to adequately meet family carer needs within palliative care, there is a lack of studies in the Australian context which examine the current type of assessment and types of care provided to family carers. The aims of this study were (1) to determine how carer needs are currently assessed and what level of support is available to family carers in three home-based palliative care services within Australia, (2) identify areas for improvement of support to carers and, (3) explore the barriers to offering carer support. A focus group and file audit were conducted at two metropolitan and one regional home-based palliative care service in Australia. These palliative care sites reported substantially different levels of services provided to family carers and also reported multiple barriers to providing services for family carers. Only one site had a formal structured procedure to assess carer needs and none of the sites used a separate carer care plan or offered a structured intervention to assist carers with their role. Family meetings were offered infrequently by most sites. A number of barriers to supporting carers were highlighted including lack of resources, and areas for improvement were also suggested by health professionals from the sites.
Gay and Bisexual Men’s Disclosure of Sexual Orientation in the Workplace: Associations With Retirement Planning
Authors: Mock Steven Edward , Sedlovskaya Alexandra , Purdie-Vaughns Valerie
Published: January 2010

This study examined the retirement financial planning of gay and bisexual men. Unlike heterosexual adults, gay and bisexual men must consider the costs and benefits of disclosing sexual identity in the workplace. Concealing sexual identity tends to diminish the appeal of the workplace and thus may increase motivation to plan for life beyond work. Analyses showed that the more participants concealed sexual orientation, the more they engaged in retirement financial planning. The results suggest that the retirement planning of gay and bisexual men is shaped by some of the typical factors established in previous research and also by their unique experience regarding sexual identity disclosure. The potential impact of concealing sexual identity on the motivation to plan for retirement is discussed.
Turkish nurses’ decision making in the distribution of intensive care beds
Authors: Ersoy Nermin , Akpinar Aslihan
Published: January 2010

The aim of this study was to assess the opinions and role of intensive care unit (ICU) nurses regarding the distribution of ICU beds. We conducted this research among 30% of the attendees at two ICU congresses in Turkey. A self-administered questionnaire was used, which included 13 cases and allocation criteria. Of the total (136 nurses), 53.7% participated in admission/discharge decisions. The most important criterion was quality of life as viewed by the physician; the least important was the patient’s social status. According to the findings, the nurses thought that medical benefit and avoiding discrimination were important. On the other hand their ignorance of patients’ autonomous preferences arouses suspicions about these nurses’ role in advocating for patients’ rights. For this reason, nurses’ role in allocation decisions should be clearly described and should also be the basis on which intensive care nurses’ duties in allocation decisions should be determined.
Patient restrictions: Are there ethical alternatives to seclusion and restraint?
Authors: Kontio Raija , Välimäki Maritta , Putkonen Hanna , Kuosmanen Lauri , Scott Anne , Joffe Grigori
Published: January 2010

The use of patient restrictions (e.g. involuntary admission, seclusion, restraint) is a complex ethical dilemma in psychiatric care. The present study explored nurses’ (n = 22) and physicians’ (n = 5) perceptions of what actually happens when an aggressive behaviour episode occurs on the ward and what alternatives to seclusion and restraint are actually in use as normal standard practice in acute psychiatric care. The data were collected by focus group interviews and analysed by inductive content analysis. The participants believed that the decision-making process for managing patients’ aggressive behaviour contains some in-built ethical dilemmas. They thought that patients’ subjective perspective received little attention. Nevertheless, the staff proposed and appeared to use a number of alternatives to minimize or replace the use of seclusion and restraint. Medical and nursing staff need to be encouraged and taught to: (1) tune in more deeply to reasons for patients’ aggressive behaviour; and (2) use alternatives to seclusion and restraint in order to humanize patient care to a greater extent.
A phenomenological study of nurses’ understanding of honesty in palliative care
Authors: Erichsen Eva , Danielsson Elisabeth Hadd , Friedrichsen Maria
Published: January 2010

Honesty is essential for the care of seriously ill and dying patients. The current study aimed to describe how nurses experience honesty in their work with patients receiving palliative care at home. The interviews in this phenomenological study were conducted with 16 nurses working with children and adults in palliative home-based care. Three categories emerged from analyses of the interviews: the meaning of honesty, the reason for being honest and, finally, moral conflict when dealing with honesty. The essence of these descriptions was that honesty is seen as a virtue, a good quality that a nurse should have. The nurses’ ethical standpoint was shown in the moral character they show in their work and in their intention to do good. This study could help nurses to identify different ways of looking at honesty to promote more consciousness and openness in ethical discussions between colleagues and other staff members.
Early MRI in optic neuritis: the risk for clinically definite multiple sclerosis
Authors: Swanton JK , Fernando KT , Dalton CM , Miszkiel KA , Altmann DR , Plant GT , Thompson AJ , Miller DH
Published: January 2010

MRI brain lesions at presentation with optic neuritis (ON) increase the risk for developing clinically definite (CD) multiple sclerosis (MS). More detailed early MRI findings may improve prediction of conversion.

The objectives of this study were to investigate the influence of number, location and activity of lesions at presentation, new lesions at early follow-up and non-lesion MRI measures on conversion from optic neuritis (ON) to CDMS.

142/143 ON patients, prospectively recruited into a serial MRI and clinical follow-up study, were followed-up at least once. Cox regression analysis determined independent early MRI predictors of time to CDMS from: (i) baseline lesion number, location and activity measures, (ii) three-month lesion activity measures and (iii) brain atrophy, magnetization transfer ratio and spectroscopy measures.

114/142 (80%) had abnormal baseline brain or cord MRI. 57 (40%) developed CDMS (median of 16 months from clinically isolated syndrome onset). Median follow-up of the non-converters was 62 months. Multivariate analysis of baseline parameters revealed gender, periventricular and gadolinium-enhancing lesions as independent predictors of CDMS. Considering both scans together, gender, baseline periventricular and new T2 lesions at follow-up remained significant (hazard ratios 2.1, 2.4 and 4.9, respectively). No non-conventional measure predicted CDMS.

It was concluded that new T2 lesions on an early follow-up scan were the strongest independent predictor of CDMS.
Bimonthly assessment of magnetization transfer magnetic resonance imaging parameters in multiple sclerosis: a 14-month, multicentre, follow-up study
Authors: Mesaros S. , Rocca MA , Sormani MP , Valsasina P. , Markowitz C. , De Stefano N. , Montalban X. , Barkhof F. , Ranjeva JP , Sailer M. , Kappos L. , Comi G. , Filippi M.
Published: January 2010

This study was performed to assess the temporal evolution of damage within lesions and the normal-appearing white matter, measured using frequent magnetization transfer (MT) MRI, in relapsing—remitting multiple sclerosis (RRMS). The relationship of MT ratio (MTR) changes with measures of lesion burden, and the sample sizes needed to demonstrate a treatment effect on MTR metrics in placebo-controlled MS trials were also investigated. Bimonthly brain conventional and MT MRI scans were acquired from 42 patients with RRMS enrolled in the placebo arm of a 14-month, double-blind trial. Longitudinal MRI changes were evaluated using a random effect linear model accounting for repeated measures, and adjusted for centre effects. The Expanded Disability Status Scale (EDSS) score remained stable over the study period. A weak, but not statistically significant, decrease over time was detected for normal-appearing brain tissue (NABT) average MTR (—0.02% per visit; p = 0.14), and MTR peak height (—0.15 per visit; p = 0.17), while average lesion MTR showed a significant decrease over the study period (—0.07% per visit; p = 0.03). At each visit, all MTR variables were significantly correlated with T2 lesion volume (LV) (average coefficients of correlation ranging from —0.54 to —0.28, and p-values from <0.001 to 0.02). At each visit, NABT average MTR was also significantly correlated with T1-hypointense LV (average coefficient of correlation = —0.57, p < 0.001). The estimation of the sample sizes required to demonstrate a reduction of average lesion MTR (the only parameter with a significant decrease over the follow-up) ranged from 101 to 154 patients to detect a treatment effect of 50% in a 1-year trial with a power of 90%. The steady correlation observed between conventional and MT MRI measures over time supports the hypothesis of axonal degeneration of fibres passing through focal lesions as one of the factors contributing to the overall MS burden.
Neurofilament light as a prognostic marker in multiple sclerosis
Authors: Salzer Jonatan , Svenningsson Anders , Sundström Peter
Published: January 2010

Relapsing-remitting multiple sclerosis has a variable prognosis and lacks a reliable laboratory prognostic marker. Our aim in this study was to investigate the association between neurofilament light levels in cerebrospinal fluid in early multiple sclerosis and disease severity at long-term follow-up. Neurofilament light levels in cerebrospinal fluid collected at diagnostic lumbar puncture were measured in 99 multiple sclerosis cases. Clinical data were obtained from 95 out of those at follow-up visits made 14 years (range 8—20 years) after disease onset. Significant correlations between neurofilament light levels and the multiple sclerosis severity score were found for all cases ( r = 0.30, p = 0.005), for relapsing-remitting multiple sclerosis cases ( r = 0.47, p < 0.001) and for cases with a recent relapse ( r = 0.60, p < 0.001). In the multivariate logistic regression analysis, neurofilament light levels >386 ng/L (median value of cases with detectable levels) increased the risk for severe multiple sclerosis fivefold (odds ratio 5.2, 95% confidence interval 1.8—15). Kaplan—Meier analysis showed that conversion to secondary-progressive multiple sclerosis was more likely in cases with neurofilament light levels >386 ng/L than in those with neurofilament light levels <60 ng/L ( p = 0.01) or 60—386 ng/L ( p = 0.03). We conclude that elevated levels of neurofilament light in cerebrospinal fluid collected at diagnostic lumbar puncture were associated with unfavourable prognosis. These data suggest that the neurofilament light level could be used as a prognostic marker in early relapsing-remitting multiple sclerosis.
Outcome measurement in multiple sclerosis: detection of clinically relevant improvement
Authors: van Winsen Lisa ML , Kragt Jolijn J , Hoogervorst Erwin LJ , Polman Chris H , Uitdehaag Bernard MJ
Published: January 2010

Because the development of new treatments in multiple sclerosis as well as the awareness of the importance of patient-oriented measures have become more important in the last two decades, new outcome measures have been developed with the aim of being more responsive to change and more clinically relevant to patients. The ability to detect improvement is sparsely studied. In the present study we evaluate the responsiveness of the Expanded Disability Status Scale and two quantitative tests (the timed 25-foot walk test and the nine-hole peg test) separately and in combination, to detect improvement after intravenous methylprednisolone. The Expanded Disability Status Scale, the timed 25-foot walk test and the nine-hole peg test were assessed in 112 multiple sclerosis patients before and 6 weeks after intravenous methylprednisolone. In addition patients were asked to rate their change as an anchor to evaluate the performance of the tests. Combining the timed 25-foot walk test and the nine-hole peg test turned out to be the optimal combination of measures to predict patient perceived improvement (positive predictive value of 67% and a negative predictive value of 59%, likelihood ratio of positive test 2.31 (95% confidence interval 1.08—4.95)). In the higher Expanded Disability Status Scale range (4.5 and higher), for all measures a significant change was more often perceived as clinically relevant than in the lower disability range. The Expanded Disability Status Scale seems not to be the preferred outcome of choice to detect patient perceived improvement in multiple sclerosis, especially in the lower Expanded Disability Status Scale range. Combining the timed walk test and the nine-hole peg test can improve the sensitivity to detect clinically relevant changes without conceding with respect to specificity.
Playing The Sims2: an exploration of gender differences in players’ motivations and patterns of play
Authors: Jansz Jeroen , Avis Corinne , Vosmeer Mirjam
Published: January 2010

The Sims is the best selling PC game of all time. It has regularly been stated that its success is partly due to its attraction to a much wider audience than the proverbial male adolescent, yet academic research on its player base is lacking. This article reports on the first ever explorative survey ( N = 760) conducted among players of The Sims2. Our study combined social role theory with gender and games theorizing to enable us to understand gender differences in play. We focused on gender differences in motivation for playing The Sims2, employing uses and gratifications as our guiding theory. Our results revealed that most of our participants were indeed female. The significantly higher score of male players on the challenge motive was anticipated by social role theory, but their higher score on social interaction was unexpected. Accordingly, we discuss the implications of our results for uses and gratifications theory as well as the necessity to investigate actual practices of play in more detail.
People Preferentially Increase Hip Joint Power Generation to Walk Faster Following Traumatic Brain Injury
Authors: Williams Gavin , Morris Meg E. , Schache Anthony , McCrory Paul R.
Published: January 2010

Background. Reduced gait speed is common following traumatic brain injury (TBI). Several studies have found that people with TBI display increased lateral movement in their center of mass while walking. It has been hypothesized that reduced gait speed following TBI is a consequence of increased caution and postural instability, but reduced ankle power generation at push-off may also play a contributing role. Objective. To determine whether postural instability or reduced muscle power were associated with reduced gait speed following TBI. Methods . A convenience sample of 55 people with TBI receiving physiotherapy for gait disorders were assessed using 3D gait analysis at self-selected and fast walking speeds. A comparison group of 10 healthy controls performed walking trials at a speed matched to the mean TBI self-selected speed and at a fast walking speed. Results. When matched for speed, people with TBI walked with similar cadence and step length but with reduced ankle power generation at push-off and increased hip power generation both in early stance and in preswing compared with healthy controls. Width of base of support and postural instability were also significantly increased for people with TBI. The differences between the 2 groups at the matched speed remained for the fast speed condition. Postural stability did not deteriorate with increasing gait speed in either group. Conclusion. Reduced gait speed following TBI appears to be attributable to biomechanical deficiencies such as reduced ankle power generation rather than reduced postural stability and increased caution.
How Employment Law Became a Major Issue for Hotel Operators
Authors: Sherwyn David
Published: January 2010

In the wake of new statutes and case law, issues relating to discrimination have expanded in the past twenty-five years to absorb a substantial amount of management time and attention. The basic law of discrimination is the Civil Rights Act of 1964, which created specific protect classes. That law was revised and expanded in 1991, and other causes of discrimination were added by such laws as the Americans with Disabilities Act and the Age Discrimination in Employment Act. Supreme Court decisions have clarified and expanded certain aspects of the laws, notably the definition of sexual harassment. Perhaps the fastest-growing complaint involves retaliation, in which employees seek to claim that unwanted employer actions result from some aspect of a civil rights complaint. While considerable confusion remains over certain aspects of discrimination law, employers should make every effort to properly instruct their supervisors and follow court-outlined procedures.
Anucleate platelets generate progeny
Authors: Schwertz Hansjörg , Köster Sarah , Kahr Walter H. A. , Michetti Noemi , Kraemer Bjoern F. , Weitz David A. , Blaylock Robert C. , Kraiss Larry W. , Greinacher Andreas , Zimmerman Guy A. , Weyrich Andrew S.
Published: January 2010

Platelets are classified as terminally differentiated cells that are incapable of cellular division. However, we observe that anucleate human platelets, either maintained in suspension culture or captured in microdrops, give rise to new cell bodies packed with respiring mitochondria and α-granules. Platelet progeny formation also occurs in whole blood cultures. Newly formed platelets are structurally indistinguishable from normal platelets, are able to adhere and spread on extracellular matrix, and display normal signal-dependent expression of surface P-selectin and annexin V. Platelet progeny formation is accompanied by increases in biomass, cellular protein levels, and protein synthesis in expanding populations. Platelet numbers also increase during ex vivo storage. These observations indicate that platelets have a previously unrecognized capacity for producing functional progeny, which involves a form of cell division that does not require a nucleus. Because this new function of platelets occurs outside of the bone marrow milieu, it raises the possibility that thrombopoiesis continues in the bloodstream.
Endothelial cell–specific chemotaxis receptor (ecscr) promotes angioblast migration during vasculogenesis and enhances VEGF receptor sensitivity
Authors: Verma Anjali , Bhattacharya Resham , Remadevi Indu , Li Keguo , Pramanik Kallal , Samant Ganesh V. , Horswill Mark , Chun Chang Z. , Zhao Baofeng , Wang Enfeng , Miao Robert Qing , Mukhopadhyay Debabrata , Ramchandran Ramani , Wilkinson George A.
Published: January 2010

Endothelial cell–specific chemotaxis receptor (ECSCR) is a cell surface protein expressed by blood endothelial cells with roles in endothelial cell migration and signal transduction. We investigated the function of ecscr in the development of the zebrafish vasculature. Zebrafish ecscr is expressed in angioblasts and in axial vessels during angioblast migration and vasculogenesis. Morpholino-directed ecscr knockdown resulted in defective angioblast migration in the posterior lateral plate mesoderm, a process known to depend on vascular endothelial-derived growth factor (VEGF). In cultured cells, transfected ECSCR localized to actin-rich membrane protrusions, colocalizing with kinase insert domain protein receptor (KDR)/VEGF receptor 2 in these regions. ECSCR-silenced cells show reduced VEGF-induced phosphorylation of KDR but not of FMS-like tyrosine kinase 1 (FLT1)/VEGF receptor 1. Finally, chemical inhibition of VEGF receptor activity in zebrafish resulted in angioblast deficiencies that partially overlap with those seen in ecscr morphants. We propose that ecscr promotes migration of zebrafish angioblasts by enhancing endothelial kdr sensitivity to VEGF.
Automatic symptom name normalization in clinical records of traditional Chinese medicine
Authors: Wang Yaqiang , Yu Zhonghua , Jiang Yongguang , Xu Kaikuo , Chen Xia
Published: January 2010

Background

In recent years, Data Mining technology has been applied more than ever before in the field of traditional Chinese medicine (TCM) to discover regularities from the experience accumulated in the past thousands of years in China. Electronic medical records (or clinical records) of TCM, containing larger amount of information than well-structured data of prescriptions extracted manually from TCM literature such as information related to medical treatment process, could be an important source for discovering valuable regularities of TCM. However, they are collected by TCM doctors on a day to day basis without the support of authoritative editorial board, and owing to different experience and background of TCM doctors, the same concept might be described in several different terms. Therefore, clinical records of TCM cannot be used directly to Data Mining and Knowledge Discovery. This paper focuses its attention on the phenomena of "one symptom with different names" and investigates a series of metrics for automatically normalizing symptom names in clinical records of TCM.

Results

A series of extensive experiments were performed to validate the metrics proposed, and they have shown that the hybrid similarity metrics integrating literal similarity and remedy-based similarity are more accurate than the others which are based on literal similarity or remedy-based similarity alone, and the highest F-Measure (65.62%) of all the metrics is achieved by hybrid similarity metric VSM+TFIDF+SWD.

Conclusions

Automatic symptom name normalization is an essential task for discovering knowledge from clinical data of TCM. The problem is introduced for the first time by this paper. The results have verified that the investigated metrics are reasonable and accurate, and the hybrid similarity metrics are much better than the metrics based on literal similarity or remedy-based similarity alone.
Genome-wide detection of predicted non-coding RNAs in Rhizobium etli expressed during free-living and host-associated growth using a high-resolution tiling array
Authors: Vercruysse Maarten , Fauvart Maarten , Cloots Lore , Engelen Kristof , Thijs Inge M , Marchal Kathleen , Michiels Jan
Published: January 2010

Background

Non-coding RNAs (ncRNAs) play a crucial role in the intricate regulation of bacterial gene expression, allowing bacteria to quickly adapt to changing environments. In the past few years, a growing number of regulatory RNA elements have been predicted by computational methods, mostly in well-studied γ-proteobacteria but lately in several α-proteobacteria as well. Here, we have compared an extensive compilation of these non-coding RNA predictions to intergenic expression data of a whole-genome high-resolution tiling array in the soil-dwelling α-proteobacterium Rhizobium etli.

Results

Expression of 89 candidate ncRNAs was detected, both on the chromosome and on the six megaplasmids encompassing the R. etli genome. Of these, 11 correspond to functionally well characterized ncRNAs, 12 were previously identified in other α-proteobacteria but are as yet uncharacterized and 66 were computationally predicted earlier but had not been experimentally identified and were therefore classified as novel ncRNAs. The latter comprise 17 putative sRNAs and 49 putative cis-regulatory ncRNAs. A selection of these candidate ncRNAs was validated by RT-qPCR, Northern blotting and 5' RACE, confirming the existence of 4 ncRNAs. Interestingly, individual transcript levels of numerous ncRNAs varied during free-living growth and during interaction with the eukaryotic host plant, pointing to possible ncRNA-dependent regulation of these specialized processes.

Conclusions

Our data support the practical value of previous ncRNA prediction algorithms and significantly expand the list of candidate ncRNAs encoded in the intergenic regions of R. etli and, by extension, of α-proteobacteria. Moreover, we show high-resolution tiling arrays to be suitable tools for studying intergenic ncRNA transcription profiles across the genome. The differential expression levels of some of these ncRNAs may indicate a role in adaptation to changing environmental conditions.
Lactobacillus acidophilus induces a slow but more sustained chemokine and cytokine response in naïve foetal enterocytes compared to commensal Escherichia coli
Authors: Zeuthen Louise H , Fink Lisbeth N , Metzdorff Stine B , Kristensen Matilde B , Licht Tine R , Nellemann Christine , Frøkiær Hanne
Published: January 2010

Background

The first exposure to microorganisms at mucosal surfaces is critical for immune maturation and gut health. Facultative anaerobic bacteria are the first to colonise the infant gut, and the impact of these bacteria on intestinal epithelial cells (IEC) may be determinant for how the immune system subsequently tolerates gut bacteria.

Results

To mirror the influence of the very first bacterial stimuli on infant IEC, we isolated IEC from mouse foetuses at gestational day 19 and from germfree neonates. IEC were stimulated with gut-derived bacteria, Gram-negativeEscherichia coliNissle and Gram-positiveLactobacillus acidophilusNCFM, and expression of genes important for immune regulation was measured together with cytokine production.E. coliNissle andL. acidophilusNCFM strongly induced chemokines and cytokines, but with different kinetics, and onlyE. coliNissle induced down-regulation of Toll-like receptor 4 and up-regulation of Toll-like receptor 2. The sensitivity to stimulation was similar before and after birth in germ-free IEC, although Toll-like receptor 2 expression was higher before birth than immediately after.

Conclusions

In conclusion, IEC isolated before gut colonisation occurs at birth, are highly responsive to stimulation with gut commensals, withL. acidophilusNCFM inducing a slower, but more sustained response thanE. coliNissle.E. colimay induce intestinal tolerance through very rapid up-regulation of chemokine and cytokine genes and down-regulation of Toll-like receptor 4, while regulating also responsiveness to Gram-positive bacteria.