bluuebunny/crossref_metadata_2025 huggingface dataset:
The NF-κB Inhibitor LC-1 Has Single Agent Activity in Multiple Myeloma Cells and Synergizes with Bortezomib
Authors: Walsby Elisabeth J. , Pratt Guy , Hewamana Saman , Crooks Peter A. , Burnett Alan K. , Fegan Chris , Pepper Chris
Published: June 2010

Multiple myeloma remains incurable with conventional therapeutics. Thus, new treatments for this condition are clearly required. In this study we evaluated the novel NF-κB inhibitor LC-1 in multiple myeloma cell lines and plasma cells derived from multiple myeloma patients. LC-1 was cytotoxic to multiple myeloma cell lines H929, U266, and JJN3, and induced apoptosis in a dose-dependent manner with an overall LD50 of 3.6 μmol/L (±1.8) after 48 hours in culture. Primary multiple myeloma cells, identified by CD38 and CD138 positivity, had a mean LD50 for LC-1 of 4.9 μmol/L (±1.6); normal bone marrow cells were significantly less sensitive to the cytotoxic effects of LC-1 (P = 0.0002). Treatment of multiple myeloma cell lines with LC-1 resulted in decreased nuclear localization of the NF-κB subunit Rel A and the inhibition of NF-κB target genes. In addition, LC-1 showed synergy with melphalan, bortezomib, and doxorubicin (combination indices of 0.72, 0.61, and 0.78, respectively), and was more effective when cells were cultured on fibronectin. These data show that LC-1 has activity in multiple myeloma cell lines and primary multiple myeloma cells, and its ability to inhibit NF-κB seems important for its cytotoxic effects. Furthermore, LC-1–induced transcriptional suppression of survivin and MCL1 provides a potential explanation for its synergy with conventional agents. Mol Cancer Ther; 9(6); 1574–82. ©2010 AACR.
Lesion Patterns of Small Deep Infarcts Have Different Clinical and Imaging Characteristics
Authors: Kim Joon-Tae , Yoon Geum-Jin , Park Man-Seok , Nam Tai-Seung , Choi Seong-Min , Lee Seung-Han , Kim Byeong-Chae , Kim Myeong-Kyu , Cho Ki-Hyun
Published: June 2010

Background: The mechanisms underlying small deep infarcts in the subcortical area are unknown. This study used coronal diffusion-weighted imaging (DWI) to investigate clinical and radiological findings in patients with small deep infarcts. Methods: This was a retrospective study of consecutively admitted patients with small deep infarcts in the subcortical area. We divided the patients into two groups as follows: (1) those with isolated lesion (IL) defined as an IL in the parenchyma by coronal DWI (group A), and (2) those with linear lesion (LL), defined as a LL extending to the basal surface on coronal DWI (group B). Results: A total of 86 patients were included in this study, with 43 patients in each group. Neurological decline and ipsilateral MCA stenosis were observed more frequently in group B than in group A. Fluid-attenuated inversion recovery (FLAIR) signals showed that white-matter hyperintensity was more severe in group A than in group B (p = 0.015). Conclusions: This study suggests that LL patterns of small deep infarcts may result in a higher rate of neurological decline and ipsilateral MCA stenosis than IL patterns.
Alcohol Consumption and Expectations of Its Effects in the Border Region of Pomerania: Comparison of German and Polish Adolescents
Authors: Zimmermann J. , Junge C. , Niemann J. , Wong J.W.M. , Preuss U.W.
Published: June 2010

The study focused on expectations of alcohol effects and patterns of consumption in German and Polish adolescents in the border region of Pomerania. In 2005/2006 a cross-sectional study was conducted in various schools. Adolescents with an average age of 14 from one German town (Greifswald) and two Polish towns (Szczecin and Kolobrzeg) were assessed using the ESPAD (European School Project on Alcohol and Other Drugs) questionnaire. Altogether 757 (444 Polish and 313 German) students in their 7th and 8th grades were assessed. Differences between alcohol consumption patterns and expectations between Germany and Poland, and relationships between alcohol consumption and anticipated alcohol effects were tested. There is a difference in patterns of consumption between the two countries. Among all adolescents, expectations of positive alcohol effects dominated, and the negative effects were estimated to be less likely. In a country-specific comparison, German students estimated the occurrence of positive as well as negative effects to be likely. Adolescents who consumed a lot of alcohol in both countries estimated the positive effects to be stronger. Adolescents are more focused on short-term experiences than the long-term consequences of alcohol consumption. The results show potential targets for prevention and intervention of future risky consumption and alcohol use disorders.
Detection of Uncommon Deletions in Alpha-Thalassemia Using the PCR-Reverse Dot-Blot Method for Prenatal Diagnosis of Nondeletional Hemoglobin H Disease
Authors: Yang Yu , Li Dong-Zhi
Published: June 2010

Nondeletional hemoglobin (Hb) H disease is caused by a deletion of both α-globin genes on one chromosome 16 and of an α+-thalassemia point mutation on the other chromosome 16. Patients with nondeletional Hb H disease are usually more anemic, more symptomatic, and are often transfused. Counseling and prenatal diagnosis ought to be offered to couples at risk of nondeletional Hb H disease. In this study, we report on the prenatal diagnoses of 2 cases of uncommon nondeletional Hb H disease using the PCR-reverse dot-blot method.
Malfunction of SynchroMed II Baclofen Pump Delivers a Near-Lethal Baclofen Overdose
Authors: Sgouros S. , Charalambides C. , Matsota P. , Tsangaris I. , Kostopanagiotou G.
Published: June 2010

Introduction: Intrathecal baclofen therapy using implantable pumps is an established treatment for spasticity. The pumps occasionally experience serious malfunction. Case Report: A 12-year-old girl suffering from spastic diplegia was implanted with a Medtronic SynchroMed II pump (Medtronic Inc., Minneapolis, Minn., USA). During a refill at 3 months 19 ml of baclofen were still in the pump. It was assumed that there was a lumbar catheter obstruction and a revision was performed. At 11 months she was receiving 180 µg/day. When she presented for refill, there were again 19 ml of baclofen in the reservoir. The pump was refilled, stopped and restarted at a lower dose. Ten minutes after restart the patient was complaining that she could not move her legs. Within the next 50 min she lapsed into coma, from a presumed baclofen overdose. She was intubated and ventilated. The reservoir was emptied of baclofen and the pump stopped. Seventeen hours after the baclofen overdose, the patient woke up gradually with no new neurological deficits. The pump was removed a week later. Medtronic laboratories examined the pump and reported no technical fault. Discussion: The implanted Medtronic SynchroMed II pump suffered an unusual malfunction. It is postulated that the pump had suffered a motor stall, and when it was restarted, it gave an unusually high, potentially lethal, dose to the patient. Conclusion: Physicians who implant pumps for intrathecal baclofen administration need to be aware that these devices may suffer unheralded catastrophic failure that can lead to potentially lethal overdose administration.
Macular Pigment Optical Density in an Ageing Irish Population: The Irish Longitudinal Study on Ageing
Authors: Nolan John M. , Kenny Roseanne , O’Regan Claire , Cronin Hilary , Loughman James , Connolly Eithne E. , Kearney Patricia , Loane Edward , Beatty Stephen
Published: June 2010

Purpose: The 3 carotenoids lutein, zeaxanthin, and meso-zeaxanthin, which account for the ‘yellow spot’ at the macula and which are referred to as macular pigment (MP), are believed to play a role in visual function and protect against age-related macular degeneration (AMD) via their optical and antioxidant properties. This study was undertaken to compare MP optical density (MPOD) in a population aged ≧50 years with MPOD values from a normative database of subjects aged 18–60 years. Methods: Seventy-nine subjects were recruited into this pilot study (The Irish Longitudinal Study on Ageing-TILDA). MPOD was measured using heterochromatic flicker photometry. Retinal fundus photographs, lifestyle data and general health data, were also obtained. Results: The mean ± SD age of the 79 subjects recruited into this study was 65 ± 11 years. There was a moderate, but statistically significant, age-related decline in MPOD at 0.5° in the TILDA data (r = –0.251, p = 0.045), which remained upon merging with a normative database of an additional 462 subjects aged between 18 and 67 years (r = –0.179, p = 0.000). Conclusions: We report an inverse association between MPOD and increasing age. Longitudinal data in a larger cohort of participants are required to satisfactorily investigate the relationship between the optical density of this pigment and age, and with risk for development and/or progression of AMD. This pilot study represents a first step in this endeavour.
Periprocedural Stroke and Management of Major Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation
Authors: Di Biase Luigi , Burkhardt J. David , Mohanty Prasant , Sanchez Javier , Horton Rodney , Gallinghouse G. Joseph , Lakkireddy Dhanunjay , Verma Atul , Khaykin Yaariv , Hongo Richard , Hao Steven , Beheiry Salwa , Pelargonio Gemma , Dello Russo Antonio , Casella Michela , Santarelli Pietro , Santangeli Pasquale , Wang Paul , Al-Ahmad Amin , Patel Dimpi , Themistoclakis Sakis , Bonso Aldo , Rossillo Antonio , Corrado Andrea , Raviele Antonio , Cummings Jennifer E. , Schweikert Robert A. , Lewis William R. , Natale Andrea
Published: June 2010

Background—

Catheter ablation of atrial fibrillation is associated with the potential risk of periprocedural stroke, which can range between 1% and 5%. We developed a prospective database to evaluate the prevalence of stroke over time and to assess whether the periprocedural anticoagulation strategy and use of open irrigation ablation catheter have resulted in a reduction of this complication.

Methods and Results—

We collected data from 9 centers performing the same ablation procedure with the same anticoagulation protocol. We divided the patients into 3 groups: ablation with an 8-mm catheter off warfarin (group 1), ablation with an open irrigated catheter off warfarin (group 2), and ablation with an open irrigated catheter on warfarin (group 3). Outcome data on stroke/transient ischemic attack and bleeding complications during and early after the procedures were collected. Of 6454 consecutive patients in the study, 2488 were in group 1, 1348 were in group 2, and 2618 were in group 3. Periprocedural stroke/transient ischemic attack occurred in 27 patients (1.1%) in group 1 and 12 patients (0.9%) in group 2. Despite a higher prevalence of nonparoxysmal atrial fibrillation and more patients with CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score >2, no stroke/transient ischemic attack was reported in group 3. Complications among groups 1, 2, and 3, including major bleeding (10 [0.4%], 11 [0.8%], and 10 [0.4%], respectively;
P
>0.05) and pericardial effusion (11 [0.4%], 11 [0.8%], and 12 [0.5%];
P
>0.05), were equally distributed.

Conclusion—

The combination of an open irrigation ablation catheter and periprocedural therapeutic anticoagulation with warfarin may reduce the risk of periprocedural stroke without increasing the risk of pericardial effusion or other bleeding complications.
Low Blood Pressure in Endothelial Cell–Specific Endothelin 1 Knockout Mice
Authors: Kisanuki Yaz Y. , Emoto Noriaki , Ohuchi Takashi , Widyantoro Bambang , Yagi Keiko , Nakayama Kazuhiko , Kedzierski Rafal M. , Hammer Robert E. , Yanagisawa Hiromi , Williams S. Clay , Richardson James A. , Suzuki Takashi , Yanagisawa Masashi
Published: June 2010

Endothelin (ET) 1 is a potent vasoconstrictor peptide produced by vascular endothelial cells and implicated in various pathophysiologic states involving abnormal vascular tone. Homozygous ET-1 null mice have craniofacial and cardiac malformations that lead to neonatal death. To study the role of ET-1 in adult vascular physiology, we generated a mouse strain (ET-1
flox/flox
;Tie2-Cre mice) in which ET-1 is disrupted specifically in endothelial cells. ET-1 peptide levels in plasma, heart, lung, kidney, and brain homogenates were reduced by 65% to 80% in these mice. mRNA levels for ET receptors were unaltered except that the ET
A
receptor mRNA was upregulated in the heart. ET-1
flox/flox
;Tie2-Cre mice had mean blood pressures 10 to 12 mm Hg lower than genetic controls. In contrast, the blood pressure of mice systemically heterozygous for the ET-1 null allele (ET-1
dlox/+
mice) was unchanged compared with wild-type littermates. Despite the lower basal blood pressure, acute pharmacological responses to angiotensin II, captopril, phenylephrine, bradykinin,
N
G
-nitro-
l
-arginine methyl ester, and exogenous ET-1 were normal in ET-1
flox/flox
;Tie2-Cre mice. These results support an essential role of endothelial-derived ET-1 in the maintenance of basal vascular tone and blood pressure. Normal pharmacological responses of ET-1
flox/flox
;Tie2-Cre mice suggest that the renin-angiotensin system, the adrenergic system, and NO are not significantly altered by endothelial ET-1. Taken in conjunction with other lines of genetically altered mice, our results provide evidence for a paracrine vasoregulatory pathway mediated by endothelial cell–derived ET-1 acting on the vascular smooth muscle ET
A
receptor.
U.S. Policy and Peacemaking Efforts in the Middle East: Historical Perspectives
Authors: Dine Thomas A.
Published: June 2010

The United States has long sought to promote a lasting peace settlement between Israel and the Arab countries. That objective has outlived the Cold War, but the Middle East was a particular flashpoint during the Cold War because of the prospect that the two superpowers might become directly involved. Moreover, the Soviet Union's strong political and military backing for Arab governments often worked against U.S. efforts to broker a peace settlement. This essay reviews two recent books that trace the history of U.S. involvement in the Middle East after the creation of Israel in 1948. The Cold War accentuated a basic problem that has persisted after the Cold War; namely, that several of the leading parties to the conflict are less intent than the United States on achieving a durable peace settlement.
On Empathy and Critical Oral History: A Commentary
Authors: Garthoff Raymond L.
Published: June 2010

Six former U.S. State Department officials, all of whom were involved in U.S. foreign policy during the Carter administration, respond to the article by James Blight and janet Lang. Their reactions vary, but one common point of concern is whether Blight and Lang are correct in arguing that “empathy” as an organizing concept or analytical tool will be useful “not just in conferences in which the past is revisited, but also in the present and future, when it really matters.” Even though most of the commentators accept at least some of the points about the U.S.-Soviet détente in the late 1970s, they have questions about the conceptual underpinnings of the article. The forum ends with a response from Blight and Lang.
Re-Animating Greg Lynn's Embryological House: A Case Study in Digital Design Preservation
Authors: Bird Lawrence , LaBelle Guillaume
Published: June 2010

Greg Lynn's Embryological House was an early work of digital architecture: a work in which the computer was a fundamental part of the design process. It was the subject of a case study in digital preservation by the Daniel Langlois Foundation's project for the Documentation and Conservation of Media Arts Heritage (DOCAM) and the Canadian Centre for Architecture (CCA). Research identified characteristics of digital architectural artifacts that are key to their long-term preservation. The results imply a shift in the focus of preservation from the artifact to its transformation in a digital context and a re-evaluation of preservation strategies and principles.
Investigating the Application of Virtual Reality Systems to Psychology and Cognitive Neuroscience Research
Authors: Annett Michelle K , Bischof Walter F
Published: June 2010

With interest in virtual reality (VR) technologies, techniques, and devices growing at a quick pace, many researchers in areas such as psychology or cognitive neuroscience want to use VR. The software and VR systems available today do not support the skill sets or experimental requirements of this group of users. We describe a number of concerns and requirements that researchers express and focus on the extent to which today's VR systems support non-VR experts. The work then concludes with a number of suggestions and potential development avenues that should be undertaken to ensure that VR systems are usable by a large range of researchers, regardless of their programming skills or technical backgrounds.
Age-related variation in threat-sensitive behavior exhibited by spotted hyenas: observational and experimental approaches
Authors: Pangle Wiline , Holekamp Kay
Published: June 2010

We examined ontogenetic variation in threat-sensitive behaviors exhibited by spotted hyenas (Crocuta crocuta). We documented naturally-occurring vigilance throughout ontogeny, and used playback experiments to evaluate age-related variation in hyenas' responses to control sounds or lion roars. We inquired whether juveniles respond to lions more cautiously than do adults. Naturalistic observations showed that juveniles are less vigilant than adults when no immediate threat is present, but more vigilant than adults when lions are present. Our playback experiments revealed that both adult and juvenile hyenas moved in response to lion roars but not to control sounds, and their reactions were stronger to roars emitted by male than female lions. However, juveniles showed a stronger response to lions than adults, as expressed by spending more time avoiding speakers after roar onset, and by having a shorter latency to first movement than adults. Like adults, juvenile hyenas, thus, appear to recognize certain signals as dangerous and respond accordingly. However, our data suggest that young hyenas may need experience with danger early in life to learn the environmental circumstances under which they ought to be vigilant when no threat is immediately apparent.
Truth, Reality and Temporality: Tractarian Visions
Authors: Bassols Alejandro Tomasini
Published: June 2010

Ludwig Wittgenstein's Tractatus Logico-Philosophicus sketches a formal view of language, reality and truth. On this account, the work only offers a purely abstract picture of the world. Wittgenstein makes clear that in order to explain the sense and the truth of our propositions we have to appeal to notions like ostension (showing) and verification. From this perspective, it turns out that everything we say is one way or another verified in the present. In particular, our past-tense propositions are verified now, i.e., in the present. Thus Wittgenstein links his formal ontology, his Picture Theory and what I refer to as his 'logical theory of truth' with an appealing solipsistic stance. From this perspective, temporality just vanishes as a feature of reality. It is always now that the world is the totality of facts.
School Counselors’ Perceptions and Experience With Acceleration as a Program Option for Gifted and Talented Students
Authors: Wood Susannah , Portman Tarrell Awe Agahe , Cigrand Dawnette L. , Colangelo Nicholas
Published: June 2010

This article presents findings from a national survey of 149 practicing school counselors who are members of the American School Counselor Association. The survey gathered information on school counselors’ perceptions of and experiences with acceleration as a program option for gifted students. Results indicate that, although school counselors’ opinions are being solicited in decision making regarding acceleration, they do not possess training and accurate information regarding acceleration. Hence, training and professional development focusing on the research-based practices of acceleration are needed to ensure that school counselors give accurate advice and guidance concerning gifted students’ education. Future research is needed to compare and contrast the effectiveness of accelerative decision making between school counselors who are trained and untrained in acceleration programmatic options.

Putting the Research to Use

School counselors are ubiquitous to schools and it is expected that they will assume an important role in the academic planning of students. In addition, they are looked to for consultation on the social and emotional development of students and how these dimensions may help or hinder academic choices. This study indicates that school counselors are prominent in the academic and social issues of gifted students when it comes to the issue of acceleration. Parents and educators do look to counselors for information and perspective regarding acceleration and counselors do provide their perspective. Also, acceleration has become a more prominent option for gifted students in schools. Unfortunately, the information and perspectives of school counselors on acceleration is not based on formal training and familiarity with the research but on informal information and limited knowledge of the research. School counselors are not well prepared to fulfill their role in helping parents, educators and students make sound decisions regarding acceleration. This study makes it clear that there is need for formal training of school counselors in the research and practice of acceleration both at the preservice and inservice levels. School counselors should participate in acceleration decisions because they bring a general and comprehensive understanding of the student. However, they need a specific understanding of acceleration in order to be effective in such decisions.
Democratization and civil war: Empirical evidence
Authors: Cederman Lars-Erik , Hug Simon , Krebs Lutz F.
Published: June 2010

The hypothesis that democratization triggers political violence has been proposed repeatedly in the quantitative literature, but it remains controversial with respect to both interstate and civil wars. Current empirical research continues to be afflicted by methodological and data problems related to the measurement of democracy and the task of detecting changes in such scores. In order to gain further clarity into the link between democratization and civil war, the current study introduces a new period-finding algorithm that is able to detect periods of democratization and autocratization. This allows for a more flexible way of finding directional changes in governance indicators than is possible with the rigid lag structures commonly employed in previous studies. When regressed on various measures of civil-war onset, the indicator for the initiation of a period of democratization has a strong and robust effect on conflict even in the presence of static measures of regime type. The same applies to autocratization, but its impact is much more sudden than that of democratization. Moreover, we find that the democratization effect is limited to governmental rather than territorial conflicts. Further research will be needed to confirm these results in terms of the relevant causal mechanisms, especially in ethno-nationalist civil wars.
Designing Cognitive Complexity in Mathematical Problem-Solving Items
Authors: Daniel Robert C. , Embretson Susan E.
Published: June 2010

Cognitive complexity level is important for measuring both aptitude and achievement in large-scale testing. Tests for standards-based assessment of mathematics, for example, often include cognitive complexity level in the test blueprint. However, little research exists on how mathematics items can be designed to vary in cognitive complexity level. In fact, determining the cognitive complexity level of items is usually based on correspondence to definitions rather than on empirically and theoretically justifiable variables that can predict item difficulty. In the current study, mathematical problem-solving items were designed for varying cognitive complexity levels based on a cognitive model of item processing. Structural variants of item models were designed to vary on two aspects of the cognitive model, the equation source and the number of subgoals. Participants were randomly assigned to test forms that contained different structural variants of the item models. Results from the linear logistic test model, the two-parameter-logistic—constrained model, and a corresponding linear mixed modeling procedure indicated that the item design variables affected both item difficulty and response time. Implications of the results for using structural variants in item generation and for the plausibility of the hypothesized cognitive model are discussed.
The corporeality of practice-based learning
Authors: Yakhlef Ali
Published: June 2010

Practice-based approaches to learning and knowing can be credited with their contribution to, among other things, establishing the social basis for human cognition, action and interaction. However, although they emphasise the (ontological) significance of practice, inter/action and activity as the basis of learning and knowing, little attention has been paid to the body — that which makes all doing and performs all action. The aim of the present study is to suggest a corporeal ground for a practice-based learning theory. The body is regarded as our link to the practical (social and material) world, and is thus the medium of learning and knowing. Drawing on Merleau-Ponty’s (1962; 1964; 1968) advanced phenomenology learning is viewed as a process of incorporating and absorbing new competencies and understandings into our body schema, which in turn transforms our ways of perceiving and acting. Learning is corporeal, pre-discursive and pre-social, stemming from the body’s perpetual need to cope with tensions arising in the body-environment connections. The study closes with some theoretical and practical implications for practice-based approaches to learning and knowing.
Evaluating Causal Explanations of Specific Events
Authors: Runde Jochen , de Rond Mark
Published: June 2010

Organizational life and research regularly involve having to explain specific events. This paper considers how such explanations might be evaluated. We outline a theory of causal explanations as answers to why-questions and introduce criteria to assess such explanations. The criteria are illustrated via an analysis of different explanations proposed for the remarkable success of Honda’s entry into the US motorcycle market.
“They Get a C-Section . . . They Gonna Die”: Somali Women’s Fears of Obstetrical Interventions in the United States
Authors: Brown Elizabeth , Carroll Jennifer , Fogarty Colleen , Holt Cristina
Published: June 2010

The authors explore sources of resistance to common prenatal and obstetrical interventions among 34 Somali resettled adult women in Rochester, New York. Results of individual interviews and focus groups with these women revealed aversion to or outright fear of cesarean sections because of fear of death and substantial resistance regarding other obstetrical interventions. Because Somali women expressed resistance to many common U.S. prenatal/obstetrical care practices, educating health professionals about Somali women’s fears and educating Somali women about common obstetrical practices are both necessary to improve maternity care for non-Bantu and Bantu Somali women.
A Long Period Grating for Simultaneous Measurement of Temperature and Strain Based on Support Vector Regression
Authors: Hu Xingliu , Liang Dakai , Zeng Jie , Lu Guan
Published: June 2010

A single long period grating is used for simultaneous measurement of temperature and strain in this article. To decrease the effect of cross-sensitivity effectively, a support vector regression (SVR) method is proposed due to its characteristics to approximate nonlinear function in the whole region. By detecting the shifts of LPG’s different loss peaks’ resonant wavelength, the temperature and strain were obtained by way of regression prediction where proper parameters were chosen. Some comparisons between the SVR and a standard matrix inversion method were made; the root-mean-square errors of two methods are 0.1746°C, 3.82 με and 2.981°C, 28.61 με, respectively. The experimental results show that SVR has advantages such as excellent learning performance of small samples, good generalization ability, small errors, high calculation accuracy, etc.
Narratives of mitigation
Authors: Jeffries Samantha , Bond Christine E.W.
Published: June 2010

In their statistical analyses of higher court sentencing in South Australia, Jeffries and Bond (2009) found evidence that Indigenous offenders were treated more leniently than non-Indigenous offenders, when they appeared before the court under similar numerical circumstances. Using a sample of narratives for criminal defendants convicted in South Australia’s higher courts, the current article extends Jeffries and Bond’s (2009) prior statistical work by drawing on the ‘focal concerns’ approach to establish whether, and in what ways, Indigeneity comes to exert a mitigating influence over sentencing. Results show that the sentencing stories of Indigenous and non-Indigenous offenders differed in ways that may have reduced assessments of blameworthiness and risk for Indigenous defendants. In addition, judges highlighted a number of Indigenous-specific constraints that potentially could result in imprisonment being construed as an overly harsh and costly sentence for Indigenous offenders.
Systematic and Engaging Early Literacy: Examining the Effects of Paraeducator Implemented Early Literacy Instruction
Authors: Bingham Gary E. , Hall-Kenyon Kendra M. , Culatta Barbara
Published: June 2010

This study examined the effect of explicit and engaging supplemental early literacy instruction on at-risk kindergarten children’s literacy development. Sixty-three kindergarten-aged children who had been ranked in the lowest 20th percentile on basic literacy skills participated in this study (38 treatment). Results reveal that children who received engaging and explicit supplemental instruction from a paraeducator performed significantly better on rhyming, alliteration, letter knowledge, letter-sound association, spelling, and blending tasks than children who received one-on-one instruction through a tutoring program. Findings highlight the important role that paraeducators can play in implementing explicit and engaging literacy curriculum that positively affects children’s development of early literacy skills.
Hypothalamic deep brain stimulation in the treatment of chronic cluster headache
Authors: Leone Massimo , Franzini Angelo , Proietti Cecchini Alberto , Broggi Giovanni , Bussone Gennaro
Published: June 2010

Cluster headache (CH) is a short-lasting unilateral headache associated with ipsilateral craniofacial autonomic manifestations. A positron emission tomography (PET) study has shown that the posterior hypothalamus is activated during CH attacks, suggesting that hypothalamic hyperactivity plays a key role in CH pathophysiology. On this basis, stimulation of the ipsilateral posterior hypothalamus was hypothesized to counteract such hyperactivity to prevent intractable CH. Ten years after its introduction, hypothalamic stimulation has been proved to successfully prevent attacks in more than 60% of 58 hypothalamic implanted drug-resistant chronic CH patients. The implantation procedure has generally been proved to be safe, although it carries a small risk of brain haemorrhage. Long-term stimulation is safe, and nonsymptomatic impairment of orthostatic adaptation is the only noteworthy change. Microrecording studies will make it possible to better identify the target site. Neuroimaging investigations have shown that hypothalamic stimulation activates ipsilateral trigeminal complex, but with no immediate perceived sensation within the trigeminal distribution. Other studies on the pain threshold in chronically stimulated patients showed increased threshold for cold pain in the distribution of the first trigeminal branch ipsilateral to stimulation. These studies suggest that activation of the hypothalamus and of the trigeminal system are both necessary, but not sufficient to generate CH attacks. In addition to the hypothalamus, other unknown brain areas are likely to play a role in the pathophysiology of this illness. Hypothalamus implantation is associated with a small risk of intracerebral haemorrhage and must be performed by an expert neurosurgical team, in selected patients.
Continuous Passive Motion, Early Weight Bearing, and Active Motion following Knee Articular Cartilage Repair
Authors: Howard Jennifer S. , Mattacola Carl G. , Romine Spencer E. , Lattermann Christian
Published: June 2010

Objective:

To systematically review the literature regarding postoperative rehabilitation for articular cartilage repair: (1) does the use of continuous passive motion (CPM) enhance healing, and if so, what parameters should be applied? (2) Can active range of motion (AROM) be used in place of or with CPM? (3) When can individuals safely resume weight bearing (WB) following repair?

Data Sources:

A search using Medline, SportsDiscus, and CINAHL databases was performed with the following keywords: articular cartilage, AROM, CPM, microfracture, osteochondral allograft, autologous chondrocyte implantation, rehabilitation, weight bearing, and knee.

Study Selection:

Basic science or clinical outcomes examining the effects of CPM, AROM, or WB on knee articular cartilage healing.

Data Extraction:

Selected articles were rated using the Strength of Recommendation Taxonomy (SORT) to determine evidence for clinical application.

Data Synthesis:

Sixteen articles met selection criteria: 12 were basic science studies; 4 were clinical studies. Basic science evidence supporting CPM exists. However, few patient-oriented outcomes have been documented resulting in a SORT rating of C. Early WB and AROM received a SORT rating of B based on limited clinical research and patient-oriented outcomes.

Conclusions:

Basic science evidence supports CPM to maintain ROM, reduce pain, and promote healing. Patient-oriented research is needed to strengthen CPM’s recommendation. Limited evidence exists regarding early WB and AROM post cartilage repair. There is insufficient evidence to confidently address when to begin WB for maximum healing. Appropriate basic science and patient-oriented research are needed for rehabilitation protocols to maximize benefits of cartilage repair procedures.
Mitochondrial cytochrome redox states and respiration in acute pulmonary oxygen sensing
Authors: Sommer N. , Pak O. , Schörner S. , Derfuss T. , Krug A. , Gnaiger E. , Ghofrani H.A. , Schermuly R.T. , Huckstorf C. , Seeger W. , Grimminger F. , Weissmann N.
Published: June 2010

Hypoxic pulmonary vasoconstriction (HPV) is an essential mechanism to optimise lung gas exchange. We aimed to decipher the proposed oxygen sensing mechanism of mitochondria in HPV.

Cytochrome redox state was assessed by remission spectrophotometry in intact lungs and isolated pulmonary artery smooth muscle cells (PASMC). Mitochondrial respiration was quantified by high-resolution respirometry. Alterations were compared with HPV and hypoxia-induced functional and molecular readouts on the cellular level. Aortic and renal arterial smooth muscle cells (ASMC and RASMC, respectively) served as controls.

The hypoxia-induced decrease of mitochondrial respiration paralleled HPV in isolated lungs. In PASMC, reduction of respiration and mitochondrial cytochrome c and aa3 (complex IV), but not of cytochrome b (complex III) matched an increase in matrix superoxide levels as well as mitochondrial membrane hyperpolarisation with subsequent cytosolic calcium increase. In contrast to PASMC, RASMC displayed a lower decrease in respiration and no rise in superoxide, membrane potential or intracellular calcium. Pharmacological inhibition of mitochondria revealed analogous kinetics of cytochrome redox state and strength of HPV.

Our data suggest inhibition of complex IV as an essential step in mitochondrial oxygen sensing of HPV. Concomitantly, increased superoxide release from complex III and mitochondrial membrane hyperpolarisation may initiate the cytosolic calcium increase underlying HPV.
Comparison of normalization methods for Illumina BeadChip HumanHT-12 v3
Authors: Schmid Ramona , Baum Patrick , Ittrich Carina , Fundel-Clemens Katrin , Huber Wolfgang , Brors Benedikt , Eils Roland , Weith Andreas , Mennerich Detlev , Quast Karsten
Published: June 2010

Background

Normalization of microarrays is a standard practice to account for and minimize effects which are not due to the controlled factors in an experiment. There is an overwhelming number of different methods that can be applied, none of which is ideally suited for all experimental designs. Thus, it is important to identify a normalization method appropriate for the experimental setup under consideration that is neither too negligent nor too stringent. Major aim is to derive optimal results from the underlying experiment. Comparisons of different normalization methods have already been conducted, none of which, to our knowledge, comparing more than a handful of methods.

Results

In the present study, 25 different ways of pre-processing Illumina Sentrix BeadChip array data are compared. Among others, methods provided by the BeadStudio software are taken into account. Looking at different statistical measures, we point out the ideal versus the actual observations. Additionally, we compare qRT-PCR measurements of transcripts from different ranges of expression intensities to the respective normalized values of the microarray data. Taking together all different kinds of measures, the ideal method for our dataset is identified.

Conclusions

Pre-processing of microarray gene expression experiments has been shown to influence further downstream analysis to a great extent and thus has to be carefully chosen based on the design of the experiment. This study provides a recommendation for deciding which normalization method is best suited for a particular experimental setup.
Are "functionally related polymorphisms" of renin-angiotensin-aldosterone system gene polymorphisms associated with hypertension?
Authors: Hahntow Ines N , Mairuhu Gideon , van Valkengoed Irene GM , Koopmans Richard P , Michel Martin C
Published: June 2010

Background

Genotype-phenotype association studies are typically based upon polymorphisms or haplotypes comprised of multiple polymorphisms within a single gene. It has been proposed that combinations of polymorphisms in distinct genes, which functionally impact the same phenotype, may have stronger phenotype associations than those within a single gene. We have tested this hypothesis using genes encoding components of the renin-angiotensin-aldosterone system and the high blood pressure phenotype.

Methods

Our analysis is based on 1379 participants of the cross-sectional SUNSET study randomly selected from the population register of Amsterdam. Each subject was genotyped for the angiotensinogen M235T, the angiotensin-converting enzyme insertion/deletion and the angiotensin II type 1 receptor A1166C polymorphism. The phenotype high blood pressure was defined either as a categorical variable comparing hypertension versus normotension as in most previous studies or as a continuous variable using systolic, diastolic and mean blood pressure in a multiple regression analysis with gender, ethnicity, age, body-mass-index and antihypertensive medication as covariates.

Results

Genotype-phenotype relationships were explored for each polymorphism in isolation and for double and triple polymorphism combinations. At the single polymorphism level, only the A allele of the angiotensin II type 1 receptor was associated with a high blood pressure phenotype. Using combinations of polymorphisms of two or all three genes did not yield stronger/more consistent associations.

Conclusions

We conclude that combinations of physiologically related polymorphisms of multiple genes, at least with regard to the renin-angiotensin-aldosterone system and the hypertensive phenotype, do not necessarily offer additional benefit in analyzing genotype/phenotype associations.
Translating the Dutch Walking Stairs, Walking Ability and Rising and Sitting Questionnaires into German and assessing their concurrent validity with VAS measures of pain and activities in daily living
Authors: Heitz Carolin , Bachmann Lucas M , Leibfried Anne , Kissling Rudolf , Kessels Alfons GH , Perez Roberto SGM , Marinus Johan , Brunner Florian
Published: June 2010

Background

The Dutch Walking Stairs, Walking Ability and Rising and Sitting Questionnaires are three validated instruments to measure physical activity and limitations in daily living in patients with lower extremity disorders living at home of which no German equivalents are available. Our scope was to translate the Walking Stairs, Walking Ability and Rising and Sitting Questionnaires into German and to verify its concurrent validity in the two domains pain and activities in daily living by comparing them with the corresponding measures on the Visual Analogue Scale.

Methods

We translated the Walking Stairs, Walking Ability and Rising and Sitting Questionnaires according to published guidelines. Demographic data and validity were assessed in 52 consecutive patients with Complex Regional Pain Syndrome 1 of the lower extremity. Information on age, duration of symptoms, type of Complex Regional Pain Syndrome 1 and type of initiating event were obtained. We assessed the concurrent validity in the two domains pain and activities in daily living by comparing them with the corresponding measures on the Visual Analogue Scale.

Results

We found that variability in the German Walking Stairs, Walking Ability and Rising and Sitting Questionnaires was largely explained by measures of pain and activities in daily living on the Visual Analogue Scale.

Conclusion

Our study shows that the domains pain and activities in daily living are properly represented in the German versions of the Walking Stairs, Walking Ability and Raising and Sitting Questionnaires. We would like to propagate their use in clinical practice and research alike.
Microprocessor of microRNAs: regulation and potential for therapeutic intervention
Authors: Beezhold Kevin J , Castranova Vince , Chen Fei
Published: June 2010

MicroRNAs (miRNAs) are a class of small, noncoding RNAs critically involved in a wide spectrum of normal and pathological processes of cells or tissues by fine-tuning the signals important for stem cell development, cell differentiation, cell cycle regulation, apoptosis, and transformation. Considerable progress has been made in the past few years in understanding the transcription, biogenesis and functional regulation of miRNAs. Numerous studies have implicated altered expression of miRNAs in human cancers, suggesting that aberrant expression of miRNAs is one of the hallmarks for carcinogenesis. In this review, we briefly discuss most recent discoveries on the regulation of miRNAs at the level of microprocessor-mediated biogenesis of miRNAs.
Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth
Authors: Yallapu Murali M , Maher Diane M , Sundram Vasudha , Bell Maria C , Jaggi Meena , Chauhan Subhash C
Published: June 2010

Background

Chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Curcumin is a naturally occurring compound with anti-cancer activity in multiple cancers; however, its chemo/radio-sensitizing potential is not well studied in ovarian cancer. Herein, we demonstrate the effectiveness of a curcumin pre-treatment strategy for chemo/radio-sensitizing cisplatin resistant ovarian cancer cells. To improve the efficacy and specificity of curcumin induced chemo/radio sensitization, we developed a curcumin nanoparticle formulation conjugated with a monoclonal antibody specific for cancer cells.

Methods

Cisplatin resistant A2780CP ovarian cancer cells were pre-treated with curcumin followed by exposure to cisplatin or radiation and the effect on cell growth was determined by MTS and colony formation assays. The effect of curcumin pre-treatment on the expression of apoptosis related proteins and β-catenin was determined by Western blotting or Flow Cytometry. A luciferase reporter assay was used to determine the effect of curcumin on β-catenin transcription activity. The poly(lactic acid-co-glycolic acid) (PLGA) nanoparticle formulation of curcumin (Nano-CUR) was developed by a modified nano-precipitation method and physico-chemical characterization was performed by transmission electron microscopy and dynamic light scattering methods.

Results

Curcumin pre-treatment considerably reduced the dose of cisplatin and radiation required to inhibit the growth of cisplatin resistant ovarian cancer cells. During the 6 hr pre-treatment, curcumin down regulated the expression of Bcl-XL and Mcl-1 pro-survival proteins. Curcumin pre-treatment followed by exposure to low doses of cisplatin increased apoptosis as indicated by annexin V staining and cleavage of caspase 9 and PARP. Additionally, curcumin pre-treatment lowered β-catenin expression and transcriptional activity. Nano-CUR was successfully generated and physico-chemical characterization of Nano-CUR indicated an average particle size of ~70 nm, steady and prolonged release of curcumin, antibody conjugation capability and effective inhibition of ovarian cancer cell growth.

Conclusion

Curcumin pre-treatment enhances chemo/radio-sensitization in A2780CP ovarian cancer cells through multiple molecular mechanisms. Therefore, curcumin pre-treatment may effectively improve ovarian cancer therapeutics. A targeted PLGA nanoparticle formulation of curcumin is feasible and may improve the in vivo therapeutic efficacy of curcumin.
The role of transposable elements in the evolution of non-mammalian vertebrates and invertebrates
Authors: Sela Noa , Kim Eddo , Ast Gil
Published: June 2010

Background

Transposable elements (TEs) have played an important role in the diversification and enrichment of mammalian transcriptomes through various mechanisms such as exonization and intronization (the birth of new exons/introns from previously intronic/exonic sequences, respectively), and insertion into first and last exons. However, no extensive analysis has compared the effects of TEs on the transcriptomes of mammals, non-mammalian vertebrates and invertebrates.

Results

We analyzed the influence of TEs on the transcriptomes of five species, three invertebrates and two non-mammalian vertebrates. Compared to previously analyzed mammals, there were lower levels of TE introduction into introns, significantly lower numbers of exonizations originating from TEs and a lower percentage of TE insertion within the first and last exons. Although the transcriptomes of vertebrates exhibit significant levels of exonization of TEs, only anecdotal cases were found in invertebrates. In vertebrates, as in mammals, the exonized TEs are mostly alternatively spliced, indicating that selective pressure maintains the original mRNA product generated from such genes.

Conclusions

Exonization of TEs is widespread in mammals, less so in non-mammalian vertebrates, and very low in invertebrates. We assume that the exonization process depends on the length of introns. Vertebrates, unlike invertebrates, are characterized by long introns and short internal exons. Our results suggest that there is a direct link between the length of introns and exonization of TEs and that this process became more prevalent following the appearance of mammals.