bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Neurofeedback Training as a Treatment for Opioid-Dependent Patients
Authors: Arani Fateme Dehghani , Rostami Reza , Nostratabadi Masoud
Published: February 2012

Neurofeedback (NF) training has been employed as a therapeutic method in substance-dependence disorder over the last three decades. The purpose of the present study was to examine the effectiveness of this method on improvement of comorbid neuro-psychological syndromes in opioid-dependence disorder. Psychopathological and craving dimensions and brain activity signals of 20 opioid dependent patients were measured using Symptom Checklist-90-Revised (SCL-90-R), Heroin Craving Questionnaire (HCQ), and Quantitative Electroencephalography (QEEG). All the patients were undergoing pharmacotherapy. They were assigned to two groups that were matched based on SCL-90-R scores, education and age. The experimental group received 30 sessions of NF training in addition to their medicine. The control group received only the usual pharmacotherapy. The probable changes were monitored by reappraisal of all the patients after the treatment. We hypothesized that patients in the experimental group would show more reduction in their comorbid syndromes.

The Multivariate Analysis of Covariance (MANCOVA) showed that the experimental group, in comparison with control group, showed significantly more improvement in all three outcome measures. In the SCL-90-R, improvement was noted with the hypochondriacs, obsession, interpersonal sensitivity, aggression, psychosis, and general symptomatic indexes. In the HCQ, improvement was found in the anticipation of positive outcome, desire to use substance, and total average score. Finally, the QEEG showed positive changes in frontal, central and parietal delta, frontal and central theta, parietal alpha and frontal and central Sensory Motor Rhythm (SMR) amplitudes.

This study suggests that NF can be used as a therapeutic method to ameliorate abnormalities related to opioid-dependence disorders. The results emphasize the importance of neuropsychological interventions in treatment of substance-dependence disorders.
Sodium Amytal Testing and the Laterality of Emotion
Authors: Trimble Michael
Published: February 2012

In this paper, the results of studies that have used the intracarotid sodium amytal (amobarbital) test to examine hemispheric lateralization of emotional expression has been reviewed. The important findings are that the emotional states are dissociated from the neurological effects (aphasia, hemiplegia), and occur later, when the electroencephalogram (EEG) is showing evidence of activation. The effects of left hemisphere barbiturization are less clear than those of the right hemisphere, and there is good concordance that the latter lead to states of alteration in mood or euphoria.
EEG Analysis of Male to Female Transsexuals: Discriminant Function and Source Analysis
Authors: Flor-Henry Pierre
Published: February 2012

A small series of consecutive, unmedicated male to female transsexuals were studied before hormonal treatment and prior to reassignment surgery. Quantitative EEG and LORETA source localization in the Eyes Open and Eyes Closed conditions were carried out, and they were compared to sinistral/ambilateral male and female controls, as the transsexual group was overwhelmingly sinistral. Discriminant function analysis and source localization showed that the transsexual group was similar to female heterosexual controls, with increased sources in the right hemisphere in the fast frequencies.
Girls with Attention-Deficit/Hyperactivity Disorder: EEG Differences between DSM-IV Types
Authors: Dupuy Franca E. , Clarke Adam R. , Barry Robert J. , McCarthy Rory , Selikowitz Mark
Published: February 2012

This study investigated EEG differences between the Combined and Inattentive types of Attention-Deficit/Hyperactivity Disorder (AD/HD) in girls.

Thirty girls with AD/HD of the Combined type, 30 girls with the Inattentive type, and 30 controls (aged 8–12 years) had a resting eyes-closed EEG recorded from 21 electrodes. The EEG was Fast Fourier Transformed and estimates for total power, and absolute and relative power in the delta, theta, alpha and beta frequency bands, were analyzed in nine cortical regions.

Across the scalp, girls with AD/HD had elevated total power, elevated absolute delta and theta, reduced relative delta and beta, and increased relative theta compared with controls. Compared with the Inattentive group, the Combined group had greater right hemisphere absolute theta and greater midline posterior absolute beta activity. The Combined group also had reduced right hemisphere relative delta, greater left hemisphere relative theta, reduced midline posterior relative alpha and reduced central relative beta activity.

In conclusion, girls with AD/HD had increased slow wave (delta and theta) activity and reduced beta activity, which are robust results in the predominantly-male AD/HD literature, and exhibited the elevated theta/beta abnormality. The lack of global differences between DSM-IV AD/HD types differs from previous studies of boys and mixed-sex groups. The present results highlight the homogeneity of EEG profiles in AD/HD girls, which could be due to sex-bias in the diagnostic criteria.

This study is the first to investigate EEG differences between the Inattentive and Combined types of AD/HD with a purely female sample.
Approaches for the Integrated Analysis of Structure, Function and Connectivity of the Human Brain
Authors: Eickhoff Simon B. , Grefkes Christian
Published: February 2012

Understanding the organization of the human brain is the fundamental prerequisite for appreciating the neural dysfunctions underlying neurological or psychiatric disorders. One major challenge in this context is the presence of multiple organizational aspects, in particular the regional differentiation in structure and function on one hand and the integration by inter-regional connectivity on the other. We here review these fundamental distinctions and introduce current methods for mapping regional specialization. The main focus of this review is to provide an overview over the different concepts and methods for assessing connections and interactions in the brain, in particular anatomical, functional and effective connectivity. In this context, we focus less on technical details and more on the comparative description of strengths and weaknesses of different aspects of connectivity as well as different methods for examining a particular aspect. This overview closes by raising several open questions on the conceptual and empirical relationship between different approaches towards understanding brain structure, function and connectivity.
EEG Theta and Alpha Reactivity on Opening the Eyes in the Diagnosis of Alzheimer's Disease
Authors: Fonseca Lineu C. , Tedrus Gloria M. A. S. , Fondello Marina A. , Reis Isabel N. , Fontoura Dayana S.
Published: February 2012

The objective of this study was to evaluate the contribution of EEG theta and alpha reactivity on opening the eyes, in the diagnosis of slight and moderate Alzheimer's disease (AD). Thirty four patients with AD and a control group of 30 individuals were studied, all being assessed using a neurological evaluation, CERAD neuropsychological battery (consortium to establish a registry for Alzheimer's disease), incorporating the Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR) and a qEEG analysis of the absolute band power at rest, with the eyes both open and closed. The theta and alpha reactivity indices were calculated on opening the eyes, defined from the relationship between the absolute powers in the respective bands in the periods with the eyes open and with them closed, the quotient of the relationship between the alpha and theta indices, the alpha/theta ratio, was also calculated. Multiple regression models were used to determine the accuracy in discriminating between the AD and control groups.

A regression model using only cognitive data provided an accuracy of 92.2%, whereas a regression model combining cognitive data and qEEG measurements provided an accuracy of 95.3% in the classification between AD and the controls. The variable for the qEEG was the left hemisphere alpha/theta index, since the other parameters were shown to be inferior with respect to the clinical data in the regression analysis.

The integrated study of the theta and alpha reactivity indices on opening the eyes and the alpha/theta index, was shown to be a useful approach in qEEG in the evaluation of AD and should be evaluated with larger samples and with other data analysis methods, with the aim of increasing the accuracy.
Brain-Computer Interface in Stroke: A Review of Progress
Authors: Silvoni Stefano , Ramos-Murguialday Ander , Cavinato Marianna , Volpato Chiara , Cisotto Giulia , Turolla Andrea , Piccione Francesco , Birbaumer Niels
Published: February 2012

Brain-computer interface (BCI) technology has been used for rehabilitation after stroke and there are a number of reports involving stroke patients in BCI-feedback training. Most publications have demonstrated the efficacy of BCI technology in post-stroke rehabilitation using output devices such as Functional Electrical Stimulation, robot, and orthosis. The aim of this review is to focus on the progress of BCI-based rehabilitation strategies and to underline future challenges. A brief history of clinical BCI-approaches is presented focusing on stroke motor rehabilitation. A context for three approaches of a BCI-based motor rehabilitation program is outlined: the substitutive strategy, classical conditioning and operant conditioning. Furthermore, we include an overview of a pilot study concerning a new neuro-forcefeedback strategy. This pilot study involved healthy participants. Finally we address some challenges for future BCI-based rehabilitation.
Somatosensory-Evoked Spikes on Electroencephalography (EEG)
Authors: Fonseca Lineu Corrêa , Tedrus Gloria M. A. S.
Published: February 2012

Somatosensory-evoked spikes (ESp) are high-voltage potentials registered on the EEG, which accompany each of the percussions on the feet or hands. The objective of this research was to study the longitudinal clinical and EEG aspects of children with ESp. A total of 313 children, 53.7% male, showing ESp on the EEG and with an average initial age of 6.82 (range from 2 to 14 years) were followed for a mean period of 35.7 months. In the initial evaluation, 118 (37.7%) had a history of nonfebrile epileptic seizures (ES). Epileptiform activity (EA) was observed on the EEG in 61% and showed a significantly greater occurrence in children with ES than in those without ( P = .000). Of the 118 showing seizures from the start, 53 (44.9%) continued to have seizures; of the 195 without seizures at the start, only 13 (6.67%) developed them. Thus, only 66 (21.1%) children showed ES during the follow-up. ESp disappeared in 237 (75.7%) cases and EA in 221 (70.6%). In the children with ES, it was found that the presence of EA on the first EEG did not indicate continuation of the ES throughout the remaining period, while the 13 children who presented their first ES in a later period showed a greater occurrence of EA on the initial EEG than those who did not develop ES ( P = .001). Evidence of brain injury was observed in 43 (13.7%) children and was associated with a greater continuity of the ES during the study ( P = .018). ESp, EA, and ES tend to disappear, suggesting an age-dependent phenomenon. The finding of ESp, particularly in the absence of any evidence of brain injury, indicates a low association with ES and benign outcome.
Mixed Methods, Triangulation, and Causal Explanation
Authors: Howe Kenneth R.
Published: February 2012

This article distinguishes a disjunctive conception of mixed methods/triangulation, which brings different methods to bear on different questions, from a conjunctive conception, which brings different methods to bear on the same question. It then examines a more inclusive, holistic conception of mixed methods/triangulation that accommodates ostensibly divergent findings by bringing them under a more comprehensive framework. Intertwined with this analysis, the article distinguishes mechanical from agential causation. Mechanical causation accounts for ordered processes of human behavior on the model of the natural sciences; agential causation accounts for ordered processes of human behavior in terms of norm-governed institutions and practices. The article concludes that there are no barriers to triangulating qualitative and quantitative methods (disjunctively or conjunctively) with respect to either mechanical or agential causation, taken separately. However, it also concludes that more comprehensive, “holistic” causal explanation that combines mechanical and agential causation, for example, explaining defiant behavior by appeal to lead poisoning, is discontinuous.
Three-component cure rate model for nonproportional hazards alternative in the design of randomized clinical trials
Authors: Kim Haesook Teresa , Gray Robert
Published: February 2012

Background Cure rate models have been extensively studied and widely used in time-to-event data in cancer clinical trials.

Purpose Although cure rate models based on the generalized exponential distribution have been developed, they have not been used in the design of randomized cancer clinical trials, which instead have relied exclusively on two-component exponential cure rate model with a proportional hazards (PH) alternative. In some studies, the efficacy of the experimental treatment is expected to emerge some time after randomization. Since this does not conform to a PH alternative, such studies require a more flexible model to describe the alternative hypothesis.

Methods In this article, we report the study design of a phase III clinical trial of acute myeloid leukemia using a three-component exponential cure rate model to reflect the alternative hypothesis. A newly developed power calculation program that does not require PH assumption was used.

Results Using a custom-made three-component cure rate model as an alternative hypothesis, the proposed sample size was 409, compared with a sample size of 209 under the assumption of exponential distribution and 228 under the PH alternative. A simulation study was performed to present the degree of power loss when the alternative hypothesis is not appropriately specified.

Limitations The power calculation program used in this study is for a single analysis and does not account for group sequential tests in phase III trials. However, the loss in power is small, and this was handled by inflating the sample size by 5%.

Conclusion Misspecification of the alternative hypothesis can result in a seriously underpowered study. We report examples of clinical trials that required a custom-made alternative hypothesis to reflect a later indication of experimental treatment efficacy. The proposed three-component cure rate model could be very useful for specifying non-PH alternative.
Grappling with social justice: Exploring new teachers’ practice and experiences
Authors: Philpott Rhonda , Dagenais Diane
Published: February 2012

This qualitative study examines the narratives of 27 new teachers as they grapple with social justice in the context of their classrooms. Informed by pedagogical perspectives regarding social justice education and new teacher mentorship, this research is framed by theories of communities of practice and professional knowledge landscapes. At the time of fieldwork, the participants had all graduated from a teacher education program focused on issues of social justice and were in their first, second or third year of teaching. Analysis of the participants’ narratives, gathered in semi-structured interviews indicates that the realities of teaching assignments, curriculum constraints and professional support either encourage or discourage new teachers from incorporating social justice into their practice. Thus, the extent to which new teachers are able to incorporate social justice into their practice can be related to the material and social conditions in which they are situated.
Citizenship education in Post-conflict contexts: A review of the literature
Authors: Quaynor Laura J.
Published: February 2012

In recent years, citizenship education has been the subject of much international attention, including two major cross-national studies. However, few reviews of civic education scholarship include research from post-conflict societies. This omission is notable because post-conflict situations offer distinct challenges to instilling both democratic norms and a sense of social cohesion to ensure democracy and social justice in the future. This paper seeks to address this need, providing a review of research on citizenship education in post-conflict contexts published in English-language journals in order to delineate similarities and differences across such contexts. Findings common to many studies on citizenship education in post-conflict countries include the avoidance of controversial issues, the unique role of ethnicity, a lack of trust in political parties and authoritarianism. Some studies also reported a movement towards global or regional identities and student desire for active citizenship education.
Service learning and active citizenship education in England
Authors: Jerome Lee
Published: February 2012

This article compares the English tradition of active citizenship education with the US tradition of service learning. It starts by outlining service learning and noting some of the defining characteristics as well as some of the tensions. It then discusses the model of active citizenship that has been promoted in England’s secondary school curriculum, considering how this has been defined and how it has been implemented. The two traditions are then compared to highlight the substantial areas of overlap between the two models, sharpen some of the distinctions and consider why there have been limited connections between them in practice. This discussion raises several issues that link to foundational questions about the nature, scope and purpose of citizenship education which are discussed in relation to the changed political context in England after the establishment of the coalition government.
Citizens fit for the 21st century? The role of school design in facilitating citizenship and self-governance in young people
Authors: Brown Jane
Published: February 2012

This article explores the relevance of school design in providing an important social-spatial context for promoting citizenship in young people. Drawing on a small-scale study that investigated the perspectives of pupils and teachers, it contrasts the ways in which the social control and monitoring of pupils differed in two secondary schools. Comparing features of everyday life in one new and one old-build school, this study found that school design could either heighten or lessen the need for teacher control of pupils. As a consequence the layout of the schools could enable or restrict young people’s opportunities for self-determination, as well as encourage the normalization of the acceptance of control by others. The implications of this for the production of autonomous and self-governing citizens will be addressed.
Reduction of severe exacerbations and hospitalization-derived costs in alpha-1-antitrypsin-deficient patients treated with alpha-1-antitrypsin augmentation therapy
Authors: Barros-Tizón Juan Carlos , Torres María Luisa , Blanco Ignacio , Martínez María Teresa ,   the investigators of the rEXA study group
Published: February 2012

Objective: Severe exacerbations in alpha-1-antitrypsin (AAT)-deficient patients with chronic obstructive pulmonary disease (COPD) and/or emphysema are a major cause of hospitalization. A multicentre, observational, retrospective study was undertaken to evaluate the effect of continuous AAT augmentation therapy in reducing the incidence of exacerbations in these patients.

Methods: Patients treated with Trypsone® or Prolastin® for at least 18 months were recruited if their medical records for 18 months before starting augmentation therapy were available. The number of mild and severe exacerbations in the two periods was compared and hospitalization-related costs were analysed.

Results: A total of 127 patients were recruited; 75 of them experienced at least one exacerbation in the period prior to augmentation. In the treatment period, the mean number of exacerbations per patient was reduced in both the total population and the population with exacerbations (mean ± SD: 1.2 ± 1.6 versus 1.0 ± 2.2 and 2.0 ± 1.6 versus 1.4 ± 2.7, respectively; p < 0.01). The percentage of patients experiencing exacerbations was reduced in the total population (59.1% versus 44.1%; p < 0.05). In the patient subgroup of the total population who experienced a change in their number of exacerbations between the two periods, 43.7% had a reduction and 21.4% had an increase ( p < 0.01). The number of severe exacerbations diminished in 42.9% of this subgroup and increased in 12.0% ( p < 0.001). Most adverse events were nonserious or not related to treatment. Hospitalization costs savings per patient associated with treatment ranged from approximately €400 to €900 ( p < 0.05).

Conclusions: Augmentation therapy with AAT concentrates was associated with a reduction in the incidence and severity of exacerbations in AAT-deficient patients, which resulted in lower hospitalization expenditures.
Vasopressin V2-receptor antagonists in patients with cirrhosis, ascites and hyponatremia
Authors: Habib Shahid , Boyer Thomas D.
Published: February 2012

Hyponatremia is a common problem in patients with advanced cirrhosis. It develops slowly (paralleling the rate of progression of the liver disease) and usually produces no neurological symptoms, although it may exacerbate hepatic encephalopathy. For patients awaiting liver transplantation a low serum sodium level is a strong predictor of pretransplant mortality, independent of the Model for End-stage Liver Disease score (MELD). The pathogenesis of hyponatremia is related to the hemodynamic changes and secondary neurohormonal adaptations that occur in patients with cirrhosis and ascites. The nonosmotic release of arginine vasopressin is the principle cause of the hyponatremia and vasopressin-receptor antagonists are a new class of drugs recently approved for treatment of cirrhotic hyponatremia. In this article we review the safety and efficacy of V2-receptor antagonists in patients with cirrhosis, ascites and hyponatremia.
Quantitative modeling of chronic myeloid leukemia: insights from radiobiology
Authors: Radivoyevitch Tomas , Hlatky Lynn , Landaw Julian , Sachs Rainer K.
Published: February 2012

Mathematical models of chronic myeloid leukemia (CML) cell population dynamics are being developed to improve CML understanding and treatment. We review such models in light of relevant findings from radiobiology, emphasizing 3 points. First, the CML models almost all assert that the latency time, from CML initiation to diagnosis, is at most ∼ 10 years. Meanwhile, current radiobiologic estimates, based on Japanese atomic bomb survivor data, indicate a substantially higher maximum, suggesting longer-term relapses and extra resistance mutations. Second, different CML models assume different numbers, between 400 and 106, of normal HSCs. Radiobiologic estimates favor values > 106 for the number of normal cells (often assumed to be the HSCs) that are at risk for a CML-initiating BCR-ABL translocation. Moreover, there is some evidence for an HSC dead-band hypothesis, consistent with HSC numbers being very different across different healthy adults. Third, radiobiologists have found that sporadic (background, age-driven) chromosome translocation incidence increases with age during adulthood. BCR-ABL translocation incidence increasing with age would provide a hitherto underanalyzed contribution to observed background adult-onset CML incidence acceleration with age, and would cast some doubt on stage-number inferences from multistage carcinogenesis models in general.
RETRACTED ARTICLE: Flavocoxid, a dual inhibitor of COX-2 and 5-LOX of natural origin, attenuates the inflammatory response and protects mice from sepsis
Authors: Bitto Alessandra , Minutoli Letteria , David Antonio , Irrera Natasha , Rinaldi Mariagrazia , Venuti Francesco S , Squadrito Francesco , Altavilla Domenica
Published: February 2012

Introduction

Cecal ligation and puncture (CLP) is an inflammatory condition that leads to multisystemic organ failure. Flavocoxid, a dual inhibitor of cyclooxygenase (COX-2) and 5-lipoxygenase (5-LOX), has been shown in vitro to possess antiinflammatory activity in lipopolysaccharide (LPS)-stimulated rat macrophages by reducing nuclear factor (NF)-κB activity and COX-2, 5-LOX and inducible nitric oxide synthase (iNOS) expression. The aim of this study was to evaluate the effects of flavocoxid in a murine model of CLP-induced polymicrobial sepsis.

Methods

C57BL/6J mice were subjected to CLP or sham operation. In a first set of experiments, an intraperitoneal injection of flavocoxid (20 mg/kg) or vehicle was administered 1 hour after surgery and repeated every 12 hours. Survival rate was monitored every 24 hours throughout 120 hours. Furthermore, additional groups of sham and CLP mice were killed 18 hours after surgical procedures for blood-sample collection and the lung and liver were collected for biomolecular, biochemical and histopathologic studies.

Results

COX-2, 5-LOX, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, extracellular-regulated-kinase 1/2 (ERK), JunN-terminal kinase (JNK), NF-κB, and β-arrestin 2 protein expression were evaluated in lung and liver with Western blot analysis. In addition, leukotriene B4 (LTB4), prostaglandin E2 (PGE2), cytokines, and lipoxin A4 serum content were measured with an enzyme-linked immunosorbent assay (ELISA). Flavocoxid administration improved survival, reduced the expression of NF-κB, COX-2, 5-LOX, TNF-α and IL-6 and increased IL-10 production. Moreover, flavocoxid inhibited the mitogen-activated protein kinases (MAPKs) pathway, preserved β-arrestin 2 expression, reduced blood LTB4, PGE2, TNF-α and IL-6, and increased IL-10 and lipoxin A4 serum levels. The treatment with flavocoxid also protected against the histologic damage induced by CLP and reduced the myeloperoxidase (MPO) activity in the lung and liver.

Conclusions

Flavocoxid protects mice from sepsis, suggesting that this dual inhibitor may represent a promising approach in such a life-threatening condition.
Three strategies to stabilise nearly monodispersed silver nanoparticles in aqueous solution
Authors: Stevenson Amadeus PZ , Blanco Bea Duani , Civit Sergi , Antoranz Contera Sonia , Iglesias Cerveto Alberto , Trigueros Sonia
Published: February 2012

Silver nanoparticles are extensively used due to their chemical and physical properties and promising applications in areas such as medicine and electronics. Controlled synthesis of silver nanoparticles remains a major challenge due to the difficulty in producing long-term stable particles of the same size and shape in aqueous solution. To address this problem, we examine three strategies to stabilise aqueous solutions of 15 nm citrate-reduced silver nanoparticles using organic polymeric capping, bimetallic core-shell and bimetallic alloying. Our results show that these strategies drastically improve nanoparticle stability by distinct mechanisms. Additionally, we report a new role of polymer functionalisation in preventing further uncontrolled nanoparticle growth. For bimetallic nanoparticles, we attribute the presence of a higher valence metal on the surface of the nanoparticle as one of the key factors for improving their long-term stability. Stable silver-based nanoparticles, free of organic solvents, will have great potential for accelerating further environmental and nanotoxicity studies.

PACS: 81.07.-b; 81.16.Be; 82.70.Dd.
Mesenchymal stem cells with rhBMP-2 inhibits the growth of canine osteosarcoma cells
Authors: Grassi Rici Rose Eli , Alcântara Dayane , Fratini Paula , Wenceslau Cristiane Valverde , Ambrósio Carlos Eduardo , Miglino Maria Angelica , Maria Durvanei Augusto
Published: February 2012

Background

The bone morphogenetic proteins (BMPs) belong to a unique group of proteins that includes the growth factor TGF-β. BMPs play important roles in cell differentiation, cell proliferation, and inhibition of cell growth. They also participate in the maturation of several cell types, depending on the microenvironment and interactions with other regulatory factors. Depending on their concentration gradient, the BMPs can attract various types of cells and act as chemotactic, mitogenic, or differentiation agents. BMPs can interfere with cell proliferation and the formation of cartilage and bone. In addition, BMPs can induce the differentiation of mesenchymal progenitor cells into various cell types, including chondroblasts and osteoblasts. The aim of this study was to analyze the effects of treatment with rhBMP-2 on the proliferation of canine mesenchymal stem cells (cMSCs) and the tumor suppression properties of rhBMP-2 in canine osteocarcoma (OST) cells. Osteosarcoma cell lines were isolated from biopsies and excisions of animals with osteosarcoma and were characterized by the Laboratory of Biochemistry and Biophysics, Butantan Institute. The mesenchymal stem cells were derived from the bone marrow of canine fetuses (cMSCs) and belong to the University of São Paulo, College of Veterinary Medicine (FMVZ-USP) stem cell bank. After expansion, the cells were cultured in a 12-well Transwell system; cells were treated with bone marrow mesenchymal stem cells associated with rhBMP2. Expression of the intracytoplasmic and nuclear markers such as Caspase-3, Bax, Bad, Bcl-2, Ki-67, p53, Oct3/4, Nanog, Stro-1 were performed by flow citometry.

Results

We evaluated the regenerative potential ofin vitrotreatment with rhBMP-2 and found that both osteogenic induction and tumor regression occur in stem cells from canine bone marrow. rhBMP-2 inhibits the proliferation capacity of OST cells by mechanisms of apoptosis and tumor suppression mediated by p53.

Conclusion

We propose that rhBMP-2 has great therapeutic potential in bone marrow cells by serving as a tumor suppressor to increase p53 and the pro-apoptotic proteins Bad and Bax, as well as by increasing the activity of phosphorylated caspase 3.

Study design

Canine bone marrow mesenchymal stem cells associated with rhBMP2 in canine osteosarcoma treatment: "in vitro" study
Family model of HIV care and treatment: a retrospective study in Kenya
Authors: Lewis Kulzer Jayne , Penner Jeremy A , Marima Reson , Oyaro Patrick , Oyanga Arbogast O , Shade Starley B , Blat Cinthia C , Nyabiage Lennah , Mwachari Christina W , Muttai Hellen C , Bukusi Elizabeth A , Cohen Craig R
Published: February 2012

Background

Nyanza Province, Kenya, had the highest HIV prevalence in the country at 14.9% in 2007, more than twice the national HIV prevalence of 7.1%. Only 16% of HIV‐infected adults in the country accurately knew their HIV status. Targeted strategies to reach and test individuals are urgently needed to curb the HIV epidemic. The family unit is one important portal.

Methods

A family model of care was designed to build on the strengths of Kenyan families. Providers use a family information table (FIT) to guide index patients through the steps of identifying family members at HIV risk, address disclosure, facilitate family testing, and work to enrol HIV‐positive members and to prevent new infections. Comprehensive family‐centred clinical services are built around these steps. To assess the approach, a retrospective study of patients receiving HIV care between September 2007 and September 2009 at Lumumba Health Centre in Kisumu was conducted. A random sample of FITs was examined to assess family reach.

Results

Through the family model of care, for each index patient, approximately 2.5 family members at risk were identified and 1.6 family members were tested. The approach was instrumental in reaching children; 61% of family members identified and tested were children. The approach also led to identifying and enrolling a high proportion of HIV‐ positive partners among those tested: 71% and 89%, respectively.

Conclusions

The family model of care is a feasible approach to broaden HIV case detection and service reach. The approach can be adapted for the local context and should continue to utilize index patient linkages, FIT adaption, and innovative methods to package services for families in a manner that builds on family support and enhances patient care and prevention efforts. Further efforts are needed to increase family member engagement.
Targeting the Interleukin-6/Jak/Stat Pathway in Human Malignancies
Authors: Sansone Pasquale , Bromberg Jacqueline
Published: February 2012

The Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway was discovered 20 years ago as a mediator of cytokine signaling. Since this time, more than 2,500 articles have been published demonstrating the importance of this pathway in virtually all malignancies. Although there are dozens of cytokines and cytokine receptors, four Jaks, and seven Stats, it seems that interleukin-6–mediated activation of Stat3 is a principal pathway implicated in promoting tumorigenesis. This transcription factor regulates the expression of numerous critical mediators of tumor formation and metastatic progression. This review will examine the relative importance and function of this pathway in nonmalignant conditions as well as malignancies (including tumor intrinsic and extrinsic), the influence of other Stats, the development of inhibitors to this pathway, and the potential role of inhibitors in controlling or eradicating cancers.
Patient Selection for Oncology Phase I Trials: A Multi-Institutional Study of Prognostic Factors
Authors: Olmos David , A'Hern Roger P. , Marsoni Silvia , Morales Rafael , Gomez-Roca Carlos , Verweij Jaap , Voest Emile E. , Schöffski Patrick , Ang Joo Ern , Penel Nicolas , Schellens Jan H. , del Conte Gianluca , Brunetto Andre T. , Evans T.R. Jeffry , Wilson Richard , Gallerani Elisa , Plummer Ruth , Tabernero Josep , Soria Jean-Charles , Kaye Stan B.
Published: February 2012

Purpose

The appropriate selection of patients for early clinical trials presents a major challenge. Previous analyses focusing on this problem were limited by small size and by interpractice heterogeneity. This study aims to define prognostic factors to guide risk-benefit assessments by using a large patient database from multiple phase I trials.

Patients and Methods

Data were collected from 2,182 eligible patients treated in phase I trials between 2005 and 2007 in 14 European institutions. We derived and validated independent prognostic factors for 90-day mortality by using multivariate logistic regression analysis.

Results

The 90-day mortality was 16.5% with a drug-related death rate of 0.4%. Trial discontinuation within 3 weeks occurred in 14% of patients primarily because of disease progression. Eight different prognostic variables for 90-day mortality were validated: performance status (PS), albumin, lactate dehydrogenase, alkaline phosphatase, number of metastatic sites, clinical tumor growth rate, lymphocytes, and WBC. Two different models of prognostic scores for 90-day mortality were generated by using these factors, including or excluding PS; both achieved specificities of more than 85% and sensitivities of approximately 50% when using a score cutoff of 5 or higher. These models were not superior to the previously published Royal Marsden Hospital score in their ability to predict 90-day mortality.

Conclusion

Patient selection using any of these prognostic scores will reduce non–drug-related 90-day mortality among patients enrolled in phase I trials by 50%. However, this can be achieved only by an overall reduction in recruitment to phase I studies of 20%, more than half of whom would in fact have survived beyond 90 days.
Isolated Tumor Cells in Regional Lymph Nodes as Relapse Predictors in Stage I and II Colorectal Cancer
Authors: Mescoli Claudia , Albertoni Laura , Pucciarelli Salvatore , Giacomelli Luciano , Russo Valentina M. , Fassan Matteo , Nitti Donato , Rugge Massimo
Published: February 2012

Purpose

Lymph node (LN) involvement is the most important prognostic factor in colorectal cancer (CRC), and pN-positive status identifies patients who require adjuvant chemotherapy. Approximately 15% to 20% of patients without nodal metastases (pN0) develop recurrent disease. In this study, we tested the prognostic significance of isolated tumor cells (ITCs) in LNs of patients with pN0 CRC (stages I and II).

Patients and Methods

ITCs in LNs regional to CRC were assessed in 312 consecutive patients with pN0 CRC who were followed up clinically and/or endoscopically for at least 6 months after surgery (mean, 67 months; median, 64 months; range, 8 to 102 months). LNs were dissected from gross surgical specimens according to a standardized protocol (with a mean of 17 LNs per patient; range, five to 107 LNs). In all, 5,313 pN0 LNs were collected and assessed by using cytokeratin immunostaining in two serial histology sections from each LN, which amounting to a total of 10,626 specimens. The correlation between ITC status and cancer recurrence was tested by using univariate and multivariate statistics.

Results

ITCs were documented in 185 of 312 patients (59%). CRC relapsed in 31 of 312 patients (10%), and 25 of 31 recurrences (81%) were documented among ITC-positive patients. CRC recurrence rates among ITC-positive and ITC-negative patients were 14% (25 of 185 patients) and 4.7% (six of 127 patients), respectively. In both univariate and multivariate analyses, ITC status was the only variable significantly associated with cancer relapse (Cox model; hazard ratio, 3.00; 95% CI, 1.23 to 7.32; P = .013).

Conclusion

In patients with pN0 CRC, cancer relapse was significantly associated with ITCs in regional LNs. ITCs should be considered among the clinicobiologic variables that identify high-risk patients who can benefit from adjuvant chemotherapy.
RNA-seq Analysis of the Functional Compartments within the Rat Placentation Site
Authors: Shankar Kartik , Zhong Ying , Kang Ping , Blackburn Michael L. , Soares Michael J. , Badger Thomas M. , Gomez-Acevedo Horacio
Published: February 2012

The rat placentation site is distinctly organized into interacting zones, the so-called labyrinth, junctional, and metrial gland compartments. These zones house unique cell populations equipped to undertake myriad prescribed functions including transport, hormonal responses, and immune interactions. Although much is known about the genesis of these cell types and specific markers that characterize each zone, a detailed global overview of gene expression in the three zones is absent. In this report, we used massively parallel sequencing (RNA-seq) to assess mRNA expression profiles and generated transcriptomic maps for each zone of the late-gestation rat placentation site (18.5 d postcoitum). Analysis of expression profiles revealed that each compartment expressed a unique signature, characterized by biological processes specific to the zone. Transport and vasculature-related processes predominated in the labyrinth, hormone secretion in the junctional, and immune interactions in the metrial gland. Furthermore, our analysis identified approximately 4000 differentially expressed genes within the zones. Using k-means clustering, we identified transcription factors with highest expression in either labyrinth, junctional, or metrial gland. Direct interaction (pathway) analysis revealed unique transcription factor networks operating in each compartment. The site-specific expression of 27 transcription factors in the three zones was ascertained via quantitative PCR and protein expression of six transcription factors was confirmed by immunohistochemistry. Finally, we elucidated the expression of key developmentally important families (Sox, GATA, Fox, Wnt, Tead, and IGF/IGFBP) in the placentation site to reveal novel expression of these several factors. The present dataset provides a novel resource to understand zonal gene expression and function in the placenta.
Using tri-axial acceleration data to identify behavioral modes of free-ranging animals: general concepts and tools illustrated for griffon vultures
Authors: Nathan Ran , Spiegel Orr , Fortmann-Roe Scott , Harel Roi , Wikelski Martin , Getz Wayne M.
Published: February 2012

Integrating biomechanics, behavior and ecology requires a mechanistic understanding of the processes producing the movement of animals. This calls for contemporaneous biomechanical, behavioral and environmental data along movement pathways. A recently formulated unifying movement ecology paradigm facilitates the integration of existing biomechanics, optimality, cognitive and random paradigms for studying movement. We focus on the use of tri-axial acceleration (ACC) data to identify behavioral modes of GPS-tracked free-ranging wild animals and demonstrate its application to study the movements of griffon vultures (Gyps fulvus, Hablizl 1783). In particular, we explore a selection of nonlinear and decision tree methods that include support vector machines, classification and regression trees, random forest methods and artificial neural networks and compare them with linear discriminant analysis (LDA) as a baseline for classifying behavioral modes. Using a dataset of 1035 ground-truthed ACC segments, we found that all methods can accurately classify behavior (80–90%) and, as expected, all nonlinear methods outperformed LDA. We also illustrate how ACC-identified behavioral modes provide the means to examine how vulture flight is affected by environmental factors, hence facilitating the integration of behavioral, biomechanical and ecological data. Our analysis of just over three-quarters of a million GPS and ACC measurements obtained from 43 free-ranging vultures across 9783 vulture-days suggests that their annual breeding schedule might be selected primarily in response to seasonal conditions favoring rising-air columns (thermals) and that rare long-range forays of up to 1750 km from the home range are performed despite potentially heavy energetic costs and a low rate of food intake, presumably to explore new breeding, social and long-term resource location opportunities.
Comparative genomics in ecological physiology: toward a more nuanced understanding of acclimation and adaptation
Authors: Whitehead Andrew
Published: February 2012

Organisms that live in variable environments must adjust their physiology to compensate for environmental change. Modern functional genomics technologies offer global top-down discovery-based tools for identifying and exploring the mechanistic basis by which organisms respond physiologically to a detected change in the environment. Given that populations and species from different niches may exhibit different acclimation abilities, comparative genomic approaches may offer more nuanced understanding of acclimation responses, and provide insight into the mechanistic and genomic basis of variable acclimation. The physiological genomics literature is large and growing, as is the comparative evolutionary genomics literature. Yet, expansion of physiological genomics experiments to exploit taxonomic variation remains relatively undeveloped. Here, recent advances in the emerging field of comparative physiological genomics are considered, including examples of plants, bees and fish, and opportunities for further development are outlined particularly in the context of climate change research. Elements of robust experimental design are discussed with emphasis on the phylogenetic comparative approach. Understanding how acclimation ability is partitioned among populations and species in nature, and knowledge of the relevant genes and mechanisms, will be important for characterizing and predicting the ecological and evolutionary consequences of human-accelerated environmental change.
Roles of transport and mixing processes in kelp forest ecology
Authors: Gaylord Brian , Nickols Kerry J. , Jurgens Laura
Published: February 2012

Fluid-dynamic transport and mixing processes affect birth, death, immigration and emigration rates in kelp forests, and can modulate broader community interactions. In the most highly studied canopy-forming kelp, Macrocystis pyrifera (the giant kelp), models of hydrodynamic and oceanographic phenomena influencing spore movement provide bounds on reproduction, quantify patterns of local and regional propagule supply, identify scales of population connectivity, and establish context for agents of early life mortality. Other analyses yield insight into flow-mediated species interactions within kelp forests. In each case, advances emerge from the use of ecomechanical approaches that propagate physical–biological connections at the scale of the individual to higher levels of ecological organization. In systems where physical factors strongly influence population, community or ecosystem properties, such mechanics-based methods promote crucial progress but are just beginning to realize their full potential.
The influence of local- and landscape-scale processes on spatial self-organization in estuarine ecosystems
Authors: van de Koppel Johan , Bouma Tjeerd J. , Herman Peter M. J.
Published: February 2012

Complexity theory proposes that spatial self-organization, the process whereby small-scale, localized interactions among the components of a system generate complex spatial structures at large spatial scales, explains the formation of autogenic spatial patterns in ecosystems. We question this premise by reviewing three estuarine ecosystems – mussel beds, mudflats and salt marshes – where self-organization has been put forward to explain spatial patterns. Our review highlights that these self-organized estuarine systems are shaped by the combination of small-scale interactions between ecological and physical processes on the one hand, and large-scale physical forcing on the other. More specifically, local interactions generate patchiness at small spatial scales, whereas landscape forcing determines the shape and orientation of these patches in the landscape. We present a framework that illustrates how self-organized ecosystems are shaped by interactions between organisms and physical processes occurring at multiple spatial scales. Moreover, the present review of estuarine systems underlines that scale-dependent feedbacks are capable of explaining spatial patterns that are much more complex than the regular patterns to which they have been applied so far.
Ode to an Ever-Open Pathway to Listening and Learning
Authors: Schwaber Evelyne Albrecht
Published: February 2012

This essay shares reflections offered by the author when she moderated a "Meet the Author" panel with James T. McLaughlin at a June 2006 meeting of the American Psychoanalytic Association, held in Washington, DC. Taking place only a few weeks before McLaughlin's death, the panel discussed his final work, The Healer's Bent: Solitude and Dialogue in the Clinical Encounter (2005), edited by William Cornell, which includes both new and some previously published writings, many reviewed here by the author. The author describes how she first met McLaughlin in 1980, when she sought him out after reading his as yet unpublished but soon-to-be classic paper, "Transference, Psychic Reality, and Countertransference," with the thesis of which—challenging the implicit hierarchy in the prevailing view of the inner experience of analyst and of patient—she felt in deep resonance. McLaughlin became for her a model of someone who, in growing older, never stopped learning and rethinking and always remained open to another way of looking at a matter, and at himself. In moderating this panel, the author, along with the other speakers, tried to convey something of the extent to which his book offers a beautiful personal, historical, theoretical, and clinical exposition of continued learning anew.