bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of SST Bias Correction on North Atlantic Hurricane Retrospective Forecasts
Authors: LaRow Timothy E.
Published: September 2012

The impact of sea surface temperature (SST) bias correction on seasonal North Atlantic hurricane retrospective forecasts is examined with the Florida State University/Center for Ocean–Atmospheric Prediction Studies (FSU/COAPS) atmospheric global spectral model. The retrospective forecasts cover a 28-yr period (1982–2009). For each year of the retrospective forecast, two, four-member ensembles are developed using predicted SSTs from the National Oceanic and Atmospheric Administration’s Climate Forecast System, version 1 (CFSv1), model. The first ensemble uses the SSTs forecasted from the CFSv1 model and the second ensemble uses the same SSTs with a simple bias correction applied. Seasonal hurricane counts determined using both SSTs are shown to have skill, although the skill is much greater using the bias-corrected SSTs. In addition, a positive significant trend in the hurricane counts is noted using the bias-corrected SSTs, in good agreement with observations while no significant trend is noted using the non-bias-corrected SST. The reason for the enhanced skill is related in part to the magnitude of the mean SST allowing stronger convective activity in the equatorial Pacific to more effectively alter the vertical wind shear in the tropical North Atlantic through changes in the Walker cell.
Mental Health Issues in Adolescents and Young Adults With Type 1 Diabetes
Authors: Bernstein Carrie M. , Stockwell Melissa S. , Gallagher Mary Pat , Rosenthal Susan L. , Soren Karen
Published: September 2012

Mental health comorbidities can negatively affect disease management in adolescents with chronic illnesses. This study sought to determine the prevalence and impact of mental health issues in a population of adolescents and young adults with type 1 diabetes. A cross-sectional study of 150 patients aged 11 to 25 years with type 1 diabetes from an urban, academic diabetes center was conducted. Participants completed 3 validated mental health disorder screening instruments: Beck’s Depression Inventory, the Screen for Child Anxiety Related Emotional Disorders-41 anxiety screen, and the Eating Disorder Screen for Primary Care. More than a third screened positive: 11.3% for depression, 21.3% for anxiety, and 20.7% for disordered eating (14.7% had ≥2 positive screens). Patients with a positive screen had twice the odds of having poor glycemic control as those without, as measured by HgbA1c. This study supports screening for mental health issues in adolescents and young adults with type 1 diabetes.
Interplay between Mesenchymal Stem Cells and Lymphocytes
Authors: Wang L. , Zhao Y. , Shi S.
Published: September 2012

In addition to their potential for replacing damaged and diseased tissues by differentiating into tissue-specific cells, mesenchymal stem cells (MSCs) have been found to interact closely with immune cells, such as lymphocytes. In this review, we will discuss current research regarding the immunomodulatory properties of MSCs and the effects of lymphocytes on MSCs. We will suggest how these findings could be translated to potential clinical treatment. MSCs can regulate immune response by inducing activated T-cell apoptosis through the FAS ligand (FASL)/FAS-mediated death pathway via cell-cell contact, leading to up-regulation of regulatory T-cells (Tregs), which ultimately results in immune tolerance. Conversely, lymphocytes can impair survival and osteogenic differentiation of implanted MSCs by secreting the pro-inflammatory cytokines IFN-γ and TNF-α and/or through the FASL/FAS-mediated death pathway, thereby negatively affecting MSC-mediated tissue regeneration. One novel strategy to improve MSC-based tissue engineering involves the reduction of IFN-γ and TNF-α concentration by systemic infusion of Tregs or local application of aspirin. Further understanding of the mechanisms underlying the interplay between lymphocytes and MSCs may be helpful in the development of promising approaches to improve cell-based regenerative medicine and immune therapies.
George F. Root’s Normal Musical Institute, 1853–1885
Authors: Hash Phillip M.
Published: September 2012

George F. Root, Lowell Mason, and William B. Bradbury opened the New York Normal Musical Institute in April of 1853 in New York City. Each term lasted about three months and provided the first long-term preparation program for singing-school masters, church choir directors, private instructors, and school music teachers in the United States. Students at the institute studied pedagogy, voice culture, music theory, and choral literature and had the opportunity to take private lessons with prominent musicians and teachers. The Normal Musical Institute relocated to North Reading, Massachusetts, in 1856 and, in 1860, began meeting in various cities throughout the country. In 1872, the school became the National Normal Musical Institute and continued under this name until its final season in Elmira, New York, in 1885. This study was designed to examine the history of this institution in relation to its origin, details of operation, pedagogy and curriculum, prominent students and faculty, and influence on music education. Data included articles from music periodicals and newspapers, pamphlets and catalogs from the institution, biographies of prominent participants, and other primary and secondary sources.
Modeling Using Discrete Event Simulation
Authors: Karnon Jonathan , Stahl James , Brennan Alan , Caro J. Jaime , Mar Javier , Möller Jörgen
Published: September 2012

Discrete event simulation (DES) is a form of computer-based modeling that provides an intuitive and flexible approach to representing complex systems. It has been used in a wide range of health care applications. Most early applications involved analyses of systems with constrained resources, where the general aim was to improve the organization of delivered services. More recently, DES has increasingly been applied to evaluate specific technologies in the context of health technology assessment. The aim of this article is to provide consensus-based guidelines on the application of DES in a health care setting, covering the range of issues to which DES can be applied. The article works through the different stages of the modeling process: structural development, parameter estimation, model implementation, model analysis, and representation and reporting. For each stage, a brief description is provided, followed by consideration of issues that are of particular relevance to the application of DES in a health care setting. Each section contains a number of best practice recommendations that were iterated among the authors, as well as the wider modeling task force.
Re-imagining postcolonial studies: a discussion of Neil Lazarus’s The Postcolonial Unconscious
Authors: Brennan Timothy
Published: September 2012

Neil Lazarus’s The Postcolonial Unconscious proposes a new literary comparatism based on a sociology of representational types rather than on modernist literary form. In this highly successful counter-text, he blasts postcolonial theory for its unacknowledged reliance on tropes and terms very alien or indifferent to the actual corpus of non-western literature. Heralding a still vibrant peripheral modernism, Lazarus pores over an extraordinarily wide range of non-western novels and poems to map an actually existing Third World aesthetic, whose political dimensions re-orient our understanding of what the postcolonial actually is.
Borderline justice
Authors: Webber Frances
Published: September 2012

This article reflects on the author’s legal career of over thirty years as a barrister representing migrants and asylum seekers in the UK. It exposes the consistently inhumane treatment meted out by successive governments to migrants and asylum seekers. It examines the ways in which such treatment is embodied in an ever-more punitive regulatory system, often implemented by powerful and profitable corporations, at the state’s behest. The hallmarks of a free society (universal rights not to be detained arbitrarily; access to justice; to fair trial; freedom from double punishment; freedom of movement) and those of a humane one (access to subsistence, shelter and health care) have all been called into question. In the service of relentless ‘common-sense’ racism, the law has been deployed against migrants and asylum seekers. However, through the sustained efforts of migrants and their solidarity groups, human rights lawyers and impartial judges, it has also been used to resist executive abuses of power, exclusion and injustice.
Sleep and Everyday Functioning in Older Adulthood
Authors: Parsey Carolyn M. , Schmitter-Edgecombe Maureen , Belenky Gregory
Published: September 2012

As individuals age they report increasing numbers of sleep problems (e.g., increased nighttime wakings) and this poorer sleep quality has been associated with increased risk for various medical conditions; however limited research has focused on the implications of sleep quality on everyday functioning in older adulthood. We compared three methods of sleep data collection (wrist actigraphy, self-report questionnaires, and sleep diary) and evaluated their relationships with three approaches to assessing everyday functioning (direct observation, self-report, and paper-and-pencil-based problem-solving tasks) in cognitively healthy older adults. Consistent with previous research, subjective sleep measures correlated significantly with each other but did not correlate with objective sleep measures. Multiple regression analyses revealed neither objective nor subjective sleep measures predicted everyday functioning. Individual variability in sleep may affect prediction of everyday functioning using a cross-sectional sample. Future research should investigate the combined influence of sleep and cognitive factors on everyday functioning in older adults.
A Population-Based Study of Physical Function and Risk for Elder Abuse Reported to Social Service Agency
Authors: Dong XinQi , Simon Melissa , Evans Denis
Published: September 2012

We examined the association between physical function and the risk for reported elder abuse. In the Chicago Health and Aging Project ( N = 8,932), 238 participants had reported elder abuse. The independent variable was objectively assessed physical function using both directly observed physical performance testing and self-reported physical function (Katz activity of daily living scale, Nagi physical activity scale, and Rosow Breslau mobility scales). Outcomes were elder abuse and specific subtypes of elder abuse. After adjusting for confounders, lower levels of physical performance testing ( OR, 2.71[1.58-4.64]), Katz impairment ( OR, 1.84[1.29-2.59]), Nagi impairment ( OR, 1.65[1.15-2.37]) and Rosow Breslau ( OR, 1.76[1.26-2.47]) were associated with increased risk for elder abuse. Lowest levels of physical performance testing were associated with increased risk for psychological abuse ( OR, 2.69[1.27-5.71]), caregiver neglect ( OR, 2.66[1.22-5.79]), and financial exploitation ( OR, 2.35 [1.21-4.55]). Our results may have important implications to healthcare professional, social services and other disciplines to prevent and treat elder abuse.
Decision-Making in Social Enterprises
Authors: Ohana Marc , Meyer Maryline , Swaton Sophie
Published: September 2012

This article studies the influence of the procedural justice resulting from participation in decision-making on employees’ affective commitment in social enterprises. It also examines whether any potential link between participation and commitment is due to social exchange, as is the case with for-profit companies. The study is based on data from employees of French work integration social enterprises. The results confirm the positive relationship between procedural justice and affective commitment and the mediating role of perceived organizational support and leader–member exchanges. Managerial recommendations are then given to best maintain or increase employees’ involvement in the decision-making processes of social enterprises.
Public Service Motivation Theory and Voluntary Organizations
Authors: Ertas Nevbahar
Published: September 2012

Research has shown that individuals with greater public service motivation (PSM) values are more likely to work for government, because government jobs offer more public service opportunities; the question then arises of whether they are also drawn into other activities that offer service opportunities, such as participation in voluntary organizations. This study examined the volunteering behavior of government employees in different domains. Using the Americans’ Changing Lives survey, logistic regression models were estimated to examine the relationship between employment in the government sector and self-reported volunteering in five different types of organization. The results indicated that government employees engage in significantly more volunteering than their private-sector counterparts. When separate models were run for volunteering in each organization type, controlling for several other factors, the results showed that these initial big differences were driven primarily by their volunteering in two specific types of organization: Educational institutions and political groups.
Flemish palliative-care nurses’ attitudes to palliative sedation
Authors: Gielen Joris , Van den Branden Stef , Van Iersel Trudie , Broeckaert Bert
Published: September 2012

Palliative sedation is an option of last resort to control refractory suffering. In order to better understand palliative-care nurses’ attitudes to palliative sedation, an anonymous questionnaire was sent to all nurses (589) employed in palliative care in Flanders (Belgium). In all, 70.5% of the nurses ( n = 415) responded. A large majority did not agree that euthanasia is preferable to palliative sedation, were against non-voluntary euthanasia in the case of a deeply and continuously sedated patient and considered it generally better not to administer artificial floods or fluids to such a patient. Two clusters were found: 58.5% belonged to the cluster of advocates of deep and continuous sedation and 41.5% belonged to the cluster of nurses restricting the application of deep and continuous sedation. These differences notwithstanding, overall the attitudes of the nurses are in accordance with the practice and policy of palliative sedation in Flemish palliative-care units.
Euthanasia and physician-assisted suicide
Authors: Tamayo-Velázquez María-Isabel , Simón-Lorda Pablo , Cruz-Piqueras Maite
Published: September 2012

The aim of this study is to assess the knowledge, attitudes and experiences of Spanish nurses in relation to euthanasia and physician-assisted suicide. In an online questionnaire completed by 390 nurses from Andalusia, 59.1% adequately identified a euthanasia situation and 64.1% a situation involving physician-assisted suicide. Around 69% were aware that both practices were illegal in Spain, while 21.4% had received requests for euthanasia and a further 7.8% for assisted suicide. A total of 22.6% believed that cases of euthanasia had occurred in Spain and 11.4% believed the same for assisted suicide. There was greater support (70%) for legalisation of euthanasia than for assisted suicide (65%), combined with a greater predisposition towards carrying out euthanasia (54%), if it were to be legalised, than participating in assisted suicide (47.3%). Nurses in Andalusia should be offered more education about issues pertaining to the end of life, and extensive research into this area should be undertaken.
Time Diversification in Developed and Emerging Markets
Authors: Anderson Hamish D. , Malone Christopher B. , Marshall Ben R.
Published: September 2012

Time in the market substantially reduces the risk of loss resulting from holding both stocks and bonds. By focusing on a downside VaR risk proxy in 25 emerging and 24 developed markets, we show that the downside risk of both stocks and bonds is greatly reduced as the investment horizon is increased beyond 10 years, but the risk reduction is more pronounced in stocks. We also show that emerging markets have substantially greater downside risk than developed markets. The results suggest that investors should be aware of their investment horizon when making asset allocation decisions, particularly into stocks in emerging markets.

JEL Classification: G14, G15
Trade-off Theory vs Pecking Order Theory Revisited
Authors: Singh Priyanka , Kumar Brajesh
Published: September 2012

This article empirically tests the two competing theories of capital structure: Trade-off theory against Pecking Order theory using the time series hypothesis. This study is performed for an emerging market context taking the case of Indian firms with a sample from 10 industries for the period 1990 to 2007. Our results support the evidence of trade-off theory in the Indian firms (contrary to the results found by Farhat, Cotei and Abugri 2006). The result is consistent for the overall sample as well as for different industries separately.

JEL Classification: G32, C23, C33
The distribution of and relationship between autistic traits and social anxiety in a UK student population
Authors: Freeth Megan , Bullock Tom , Milne Elizabeth
Published: September 2012

Traits associated with autism and social anxiety were assessed in a UK student population (n = 1325) using the Autism-spectrum Quotient and the Liebowitz Social Anxiety Scale. Clinically relevant levels of autistic traits were observed in 3.3% of the cohort; 10.1% of the cohort reported clinically relevant levels of social anxiety; 1.8% of the cohort met clinically relevant cut-offs for both conditions. There was a significant positive correlation between scores on the two scales (r = .51); students with high levels of autistic traits were more likely to report increased social anxiety than those with average or low levels of autistic traits. Level of social anxiety was best predicted by autistic traits associated with social skill, attention switching and communication, accounting for 33% of the variance in social anxiety scores. Social skill was a better predictor of social anxiety in males than females; attention switching ability was a better predictor of social anxiety in females than males. Students with high levels of autistic traits displayed heightened anxiety to situations and activities necessary for the successful completion of their degree. Implications for student well-being and attainment are discussed.
Adaptive function in preschoolers in relation to developmental delay and diagnosis of autism spectrum disorders: Insights from a clinical sample
Authors: Milne Susan L , McDonald Jenny L , Comino Elizabeth J
Published: September 2012

This study aims to explore the relationship between developmental ability, autism and adaptive skills in preschoolers. Adaptive function was assessed in 152 preschoolers with autism, with and without developmental delay, and without autism, with and without developmental delay. Their overall adaptive function, measured by the general adaptive composite on the Adaptive Behaviour Assessment System, was closely correlated to developmental ability as measured by the general quotient on the Griffith Mental Development Scales. Children with autism performed significantly less well on both scales. Domain scores discriminated between children with and without autism, with poorer performance on both the social and practical domain scores for children with autism, even when controlling for the effects of development. Children with average development, both with and without autism, had lower adaptive skills than expected for their developmental level. The importance of considering domain scores as well as the general adaptive composite when determining support needs is emphasised.
Ontological quarrels: Indigeneity, exclusion and citizenship in a relational world
Authors: Salmond Anne
Published: September 2012

In settler societies such as New Zealand, the relationships between indigenous groups and settlers whose ancestors arrived from Europe involve clashes and exchanges between those who hold different sets of presuppositions about how the world works. In early New Zealand, Māori and Europeans often found themselves at ontological cross-purposes, and such contestations are still common. In this paper, I explore fundamental divergences and resonances between ancestral Māori and modernist ontological styles, and how over the past two hundred years these have emerged in debates over the Treaty of Waitangi, signed between Māori rangatira (chiefs) and the British Crown in 1840; and over tapu (the sacred, or state of ancestral presence), land, citizenship and mana or power.
The pitch of ethnography: Language, relations, and the significance of listening
Authors: Myhre Knut Christian
Published: September 2012

This article explores social anthropology’s relationship to, and conception of, language, and uses kinship as an example to show how the discipline presumes and entails a digital conception of social relations, which leaves little room for language as a constitutive phenomenon. By drawing on certain philosophies of language, the article deploys the notion of pitch to explore the published ethnography on the Lovedu of South Africa to show how language is constitutive of social relations and the manner in which these can be conceived of as analogue phenomena. On this basis, it is argued that language must be added to recent approaches as a central concern for kinship studies. Furthermore, it is held that the activity of listening can reconfigure our approach to, and conception of, language to attune ethnography to vernacular conceptual analyses.
Teaching close reading: A VLE-based approach
Authors: Adlington Hugh , Wright Gillian
Published: September 2012

This article discusses the effectiveness of using an approach based on a virtual learning environment (VLE) to enhance the close-reading skills of first-year English undergraduates. The first two sections explore the practical and theoretical issues involved in adopting such an approach; the third describes the design and functions of a VLE close-reading resource designed for this purpose; and the fourth and fifth elucidate the methodology and findings of a two-year research project which aimed to evaluate the resource’s effectiveness. Analysis of the findings shows: first, that student usage of the resource is significantly enhanced by tutor recommendation; second, that student usage strategies are highly instrumental (i.e. that students disproportionately choose texts likely to feature in the end-of-year exam); and third, that the expansion of the number of particular kinds of worked examples would increase the usefulness of the resource. The implications of these findings for use of the VLE resource are discussed.
Curing type 2 diabetes mellitus with bariatric surgery - reality or delusion?
Authors: Davies Andrew R , Efthimiou Evangelos
Published: September 2012

Bariatric surgery is known to have profound effects on type 2 diabetes mellitus, yet only a fraction of eligible patients will be considered for this type of intervention. In the UK, eligibility criteria for surgery are becoming increasingly strict and diabetes has emerged as the most important comorbid indication for surgery in the obese patient. This review examines current evidence for bariatric surgery in obese diabetic patients with a view to raising the profile of this life changing intervention.
Paucity of IL-21–producing CD4+ T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques
Authors: Micci Luca , Cervasi Barbara , Ende Zachary S. , Iriele Robin I. , Reyes-Aviles Elane , Vinton Carol , Else James , Silvestri Guido , Ansari Aftab A. , Villinger Francois , Pahwa Savita , Estes Jacob D. , Brenchley Jason M. , Paiardini Mirko
Published: September 2012

IL-21 regulates Th17 cell homeostasis, enhances the differentiation of memory B cells and antibody-secreting plasma cells, and promotes the maintenance of CD8+ T-cell responses. In this study, we investigated the phenotype, function, and frequency of blood and intestinal IL-21–producing cells in nonhuman primates that are hosts of progressive (rhesus macaques [RMs]) and nonprogressive (sooty mangabeys [SMs]) SIV infection. We found that, in both species, memory CD4+CD95+CCR6− T cells are the main IL-21 producers, and that only a small fraction of CD4+IL-21+ T cells produce IL-17. During chronic SIV infection of RMs, CD4+IL-21+ T cells were significantly depleted in both blood and rectal mucosa, with the extent of this depletion correlating with the loss of Th17 cells. Furthermore, treatment with IL-21 increased the in vivo levels of Th17 cells in SIV-infected RMs. In contrast, normal levels of CD4+IL-21+ T cells were found in SIV-infected SMs. Collectively, these data indicate that depletion of IL-21–producing CD4+ T cells distinguishes progressive from nonprogressive SIV infection of RMs and SMs, and suggest that depletion of CD4+IL-21+ T cells is involved in the preferential loss of Th17 cells that is associated with SIV disease progression. Further preclinical studies of IL-21 as a potential immunotherapeutic agent for HIV infection may be warranted.
Extracytoplasmic function (ECF) sigma factor σF is involved in Caulobacter crescentus response to heavy metal stress
Authors: Kohler Christian , Lourenço Rogério F , Avelar Gabriela M , Gomes Suely L
Published: September 2012

Background

The α-proteobacterium Caulobacter crescentus inhabits low-nutrient environments and can tolerate certain levels of heavy metals in these sites. It has been reported that C. crescentus responds to exposure to various heavy metals by altering the expression of a large number of genes.

Results

In this work, we show that the ECF sigma factor σF is one of the regulatory proteins involved in the control of the transcriptional response to chromium and cadmium. Microarray experiments indicate that σF controls eight genes during chromium stress, most of which were previously described as induced by heavy metals. Surprisingly, σF itself is not strongly auto-regulated under metal stress conditions. Interestingly, σF-dependent genes are not induced in the presence of agents that generate reactive oxygen species. Promoter analyses revealed that a conserved σF-dependent sequence is located upstream of all genes of the σF regulon. In addition, we show that the second gene in the sigF operon acts as a negative regulator of σF function, and the encoded protein has been named NrsF (Negative regulator of sigma F). Substitution of two conserved cysteine residues (C131 and C181) in NrsF affects its ability to maintain the expression of σF-dependent genes at basal levels. Furthermore, we show that σF is released into the cytoplasm during chromium stress and in cells carrying point mutations in both conserved cysteines of the protein NrsF.

Conclusion

A possible mechanism for induction of the σF-dependent genes by chromium and cadmium is the inactivation of the putative anti-sigma factor NrsF, leading to the release of σF to bind RNA polymerase core and drive transcription of its regulon.
The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2
Authors: Cline Brandon H , Steinbusch Harry WM , Malin Dmitry , Revishchin Alexander V , Pavlova Galia V , Cespuglio Raymond , Strekalova Tatyana
Published: September 2012

Background

A number of epidemiological studies have established a link between insulin resistance and the prevalence of depression. The occurrence of depression was found to precede the onset of diabetes and was hypothesized to be associated with inherited inter-related insufficiency of the peripheral and central insulin receptors. Recently, dicholine succinate, a sensitizer of the neuronal insulin receptor, was shown to stimulate insulin-dependent H2O2production of the mitochondrial respiratory chain leading to an enhancement of insulin receptor autophosphorylation in neurons. As such, this mechanism can be a novel target for the elevation of insulin signaling.

Results

Administration of DS (25 mg/kg/day, intraperitoneal) in CD1 mice for 7 days prior to the onset of stress procedure, diminished manifestations of anhedonia defined in a sucrose test and behavioral despair in the forced swim test. Treatment with dicholine succinate reduced the anxiety scores of stressed mice in the dark/light box paradigm, precluded stress-induced decreases of long-term contextual memory in the step-down avoidance test and hippocampal gene expression of IGF2.

Conclusions

Our data suggest that dicholine succinate has an antidepressant-like effect, which might be mediated via the up-regulation of hippocampal expression of IGF2, and implicate the neuronal insulin receptor in the pathogenesis of stress-induced depressive syndrome.
In-house preparation of hydrogels for batch affinity purification of glutathione S-transferase tagged recombinant proteins
Authors: Buhrman Jason S , Rayahin Jamie E , Köllmer Melanie , Gemeinhart Richard A
Published: September 2012

Background

Many branches of biomedical research find use for pure recombinant proteins for direct application or to study other molecules and pathways. Glutathione affinity purification is commonly used to isolate and purify glutathione S-transferase (GST)-tagged fusion proteins from total cellular proteins in lysates. Although GST affinity materials are commercially available as glutathione immobilized on beaded agarose resins, few simple options for in-house production of those systems exist. Herein, we describe a novel method for the purification of GST-tagged recombinant proteins.

Results

Glutathione was conjugated to low molecular weight poly(ethylene glycol) diacrylate (PEGDA) via thiol-ene “click” chemistry. With our in-house prepared PEGDA:glutathione (PEGDA:GSH) homogenates, we were able to purify a glutathione S-transferase (GST) green fluorescent protein (GFP) fusion protein (GST-GFP) from the soluble fraction of E. coli lysate. Further, microspheres were formed from the PEGDA:GSH hydrogels and improved protein binding to a level comparable to purchased GSH-agarose beads.

Conclusions

GSH containing polymers might find use as in-house methods of protein purification. They exhibited similar ability to purify GST tagged proteins as purchased GSH agarose beads.
Conjunctival lymphoma arising from reactive lymphoid hyperplasia
Authors: Fukuhara Junichi , Kase Satoru , Noda Mika , Ishijima Kan , Yamamoto Teppei , Ishida Susumu
Published: September 2012

Extra nodal marginal zone B-cell lymphoma (EMZL) of the conjunctiva typically arises in the marginal zone of mucosa-associated lymphoid tissue. The pathogenesis of conjunctival EMZL remains unknown. We describe an unusual case of EMZL arising from reactive lymphoid hyperplasia (RLH) of the conjunctiva. A 35-year-old woman had fleshy salmon-pink conjunctival tumors in both eyes, oculus uterque (OU). Specimens from conjunctival tumors in the right eye, oculus dexter (OD), revealed a collection of small lymphoid cells in the stroma. Immunohistochemically, immunoglobulin (Ig) light chain restriction was not detected. In contrast, diffuse atypical lymphoid cell infiltration was noted in the left eye, oculus sinister (OS), and positive for CD20, a marker for B cells OS. The tumors were histologically diagnosed as RLH OD, and EMZL OS. PCR analysis detected IgH gene rearrangement in the joining region (JH) region OU. After 11 months, a re-biopsy specimen demonstrated EMZL based on compatible pathological and genetic findings OD, arising from RLH. This case suggests that even if the diagnosis of the conjunctival lymphoproliferative lesions is histologically benign, confirmation of the B-cell clonality by checking IgH gene rearrangement should be useful to predict the incidence of malignancy.
Surface-downhole electrical resistivity tomography applied to monitoring of CO2 storage at Ketzin, Germany
Authors: Bergmann Peter , Schmidt-Hattenberger Cornelia , Kiessling Dana , Rücker Carsten , Labitzke Tim , Henninges Jan , Baumann Gunther , Schütt Hartmut
Published: September 2012

Surface-downhole electrical resistivity tomography (SD-ERT) surveys were repeatedly carried out to image [Formula: see text] injected at the pilot storage Ketzin, Germany. The experimental setup combines surface with downhole measurements by using a permanent electrode array that has been deployed in three wells. Two baseline experiments were performed during the site startup and three repeat experiments were performed during the first year of CO2 injection. By the time of the third repeat, approximately 13,500 tons of [Formula: see text] had been injected into the reservoir sandstones at about 650 m depth. Field data and inverted resistivity models showed a resistivity increase over time at the [Formula: see text] injector. The lateral extent of the related resistivity signature indicated a preferential [Formula: see text] migration toward the northwest. Using an experimental resistivity-saturation relationship, we mapped [Formula: see text] saturations by means of the resistivity index method. For the latest repeat, [Formula: see text] saturations show values of up to 70% near the injection well, which matches well with [Formula: see text] saturations determined from pulsed neutron-gamma logging. The presence of environmental noise, reservoir heterogeneities, and irregularities in the well completions are the main sources of uncertainty for the interpretations. The degradation of the permanently installed downhole components is monitored by means of frequently performed resistance checks. In consistency with the SD-ERT data, these resistance checks indicate a long-term resistivity increase near the [Formula: see text] injector. In conclusion, the investigations demonstrate the capability of surface-downhole electrical resistivity tomography to image geologically stored [Formula: see text] at the Ketzin site.
Seven-Year Follow-Up Assessment of Cardiac Function in NSABP B-31, a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel (ACP) With ACP Plus Trastuzumab As Adjuvant Therapy for Patients With Node-Positive, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: Romond Edward H. , Jeong Jong-Hyeon , Rastogi Priya , Swain Sandra M. , Geyer Charles E. , Ewer Michael S. , Rathi Vikas , Fehrenbacher Louis , Brufsky Adam , Azar Catherine A. , Flynn Patrick J. , Zapas John L. , Polikoff Jonathan , Gross Howard M. , Biggs David D. , Atkins James N. , Tan-Chiu Elizabeth , Zheng Ping , Yothers Greg , Mamounas Eleftherios P. , Wolmark Norman
Published: September 2012

Purpose

Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2–positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care.

Patients and Methods

In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified.

Results

At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab.

Conclusion

The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab.
L-Carnitine Supplementation for the Management of Fatigue in Patients With Cancer: An Eastern Cooperative Oncology Group Phase III, Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Cruciani Ricardo A. , Zhang Jenny J. , Manola Judith , Cella David , Ansari Bilal , Fisch Michael J.
Published: September 2012

Purpose

L-carnitine, a popular complementary and alternative medicine product, is used by patients with cancer for the treatment of fatigue, the most commonly reported symptom in this patient population. The purpose of this study was to determine the efficacy of L-carnitine supplementation as a treatment for fatigue in patients with cancer.

Patients and Methods

In this double-blind, placebo-controlled trial, patients with invasive malignancies and fatigue were randomly assigned to either 2 g/d of L-carnitine oral supplementation or matching placebo. The primary end point was the change in average daily fatigue from baseline to week 4 using the Brief Fatigue Inventory (BFI).

Results

Three hundred seventy-six patients were randomly assigned to treatment with L-carnitine supplementation or placebo. L-carnitine supplementation resulted in significant carnitine plasma level increase by week 4. The primary outcome, fatigue, measured using the BFI, improved in both arms compared with baseline (L-carnitine: −0.96, 95% CI, −1.32 to −0.60; placebo: −1.11, 95% CI −1.44 to −0.78). There were no statistically significant differences between arms (P = .57). Secondary outcomes, including fatigue measured by the Functional Assessment of Chronic Illness Therapy–Fatigue instrument, depression, and pain, did not show significant difference between arms. A separate analysis of patients who were carnitine-deficient at baseline did not show statistically significant improvement in fatigue or other outcomes after L-carnitine supplementation.

Conclusion

Four weeks of 2 g of L-carnitine supplementation did not improve fatigue in patients with invasive malignancies and good performance status.
Adverse Prognostic Impact of Intratumor Heterogeneous HER2 Gene Amplification in Patients With Esophageal Adenocarcinoma
Authors: Yoon Harry H. , Shi Qian , Sukov William R. , Lewis Mark A. , Sattler Christopher A. , Wiktor Anne E. , Wu Tsung-Teh , Diasio Robert B. , Jenkins Robert B. , Sinicrope Frank A.
Published: September 2012

Purpose

There is increasing recognition of the existence of intratumoral heterogeneity of the human epidermal growth factor receptor (HER2), which affects interpretation of HER2 positivity in clinical practice and may have implications for patient prognosis and treatment. We determined the frequency and prognostic impact of heterogeneous HER2 gene amplification and polysomy 17 in patients with esophageal adenocarcinoma (EAC).

Patients and Methods

HER2 amplification (by fluorescence in situ hybridization) was examined in surgical EAC specimens (n = 675). HER2 heterogeneity was defined according to consensus guidelines as gene amplification (HER2/CEP17 ratio ≥ 2.0) in more than 5% but less than 50% of cancer cells. No patient received neoadjuvant or HER2-targeted therapy. Cox models were used to assess disease-specific survival (DSS) and overall survival (OS).

Results

Overall, 117 EACs (17%) demonstrated HER2 amplification, of which 20 (17%) showed HER2 heterogeneity. All HER2-heterogeneous tumors were amplified. Among HER2-amplified tumors, heterogeneous tumors had significantly higher frequency of poor histologic grade and polysomy 17. In multivariable models that included number of metastatic lymph nodes, grade, tumor stage, and polysomy 17, only HER2 heterogeneity and node number were prognostic among HER2-amplified tumors, with heterogeneity showing worse DSS (hazard ratio, 2.04; 95% CI, 1.09 to 3.79; P = .025) and OS (P = .026). Among HER2-nonamplified EACs, polysomy 17 was independently associated with worse DSS (P = .012) and OS (P = .023).

Conclusion

Among HER2-amplified EACs, 17% show HER2 heterogeneity, which independently predicts for worse cancer-specific death. Among HER2-nonamplified EACs, polysomy 17 is independently associated with worse survival. These novel findings demonstrate aggressive subgroups in HER2-amplified and -nonamplified EACs that have important implications for HER2 analysis and determination of benefit from HER2-targeted therapy.
Prognostic Significance of the European LeukemiaNet Standardized System for Reporting Cytogenetic and Molecular Alterations in Adults With Acute Myeloid Leukemia
Authors: Mrózek Krzysztof , Marcucci Guido , Nicolet Deedra , Maharry Kati S. , Becker Heiko , Whitman Susan P. , Metzeler Klaus H. , Schwind Sebastian , Wu Yue-Zhong , Kohlschmidt Jessica , Pettenati Mark J. , Heerema Nyla A. , Block AnneMarie W. , Patil Shivanand R. , Baer Maria R. , Kolitz Jonathan E. , Moore Joseph O. , Carroll Andrew J. , Stone Richard M. , Larson Richard A. , Bloomfield Clara D.
Published: September 2012

Purpose

To evaluate the prognostic significance of the international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML).

Patients and Methods

We analyzed 1,550 adults with primary AML, treated on Cancer and Leukemia Group B first-line trials, who had pretreatment cytogenetics and, for cytogenetically normal patients, mutational status of NPM1, CEBPA, and FLT3 available. We compared complete remission (CR) rates, disease-free survival (DFS), and overall survival (OS) among patients classified into the four ELN genetic groups (favorable, intermediate-I, intermediate-II, adverse) separately for 818 younger (age < 60 years) and 732 older (age ≥ 60 years) patients.

Results

The percentages of younger versus older patients in the favorable (41% v 20%; P < .001), intermediate-II (19% v 30%; P < .001), and adverse (22% v 31%; P < .001) genetic groups differed. The favorable group had the best and the adverse group the worst CR rates, DFS, and OS in both age groups. Both intermediate groups had significantly worse outcomes than the favorable but better than the adverse group. Intermediate-I and intermediate-II groups in older patients had similar outcomes, whereas the intermediate-II group in younger patients had better OS but not better CR rates or DFS than the intermediate-I group. The prognostic significance of ELN classification was confirmed by multivariable analyses. For each ELN group, older patients had worse outcomes than younger patients.

Conclusion

The ELN classification clearly separates the genetic groups by outcome, supporting its use for risk stratification in clinical trials. Because they have different proportions of genetic alterations and outcomes, younger and older patients should be reported separately when using the ELN classification.
Ectodomain shedding and ADAMs in development
Authors: Weber Silvio , Saftig Paul
Published: September 2012

Proteolytic enzymes belonging to the A Disintegin And Metalloproteinase (ADAM) family are able to cleave transmembrane proteins close to the cell surface, in a process referred to as ectodomain shedding. Substrates for ADAMs include growth factors, cytokines, chemokines and adhesion molecules, and, as such, many ADAM proteins play crucial roles in cell-cell adhesion, extracellular and intracellular signaling, cell differentiation and cell proliferation. In this Review, we summarize the fascinating roles of ADAMs in embryonic and adult tissue development in both vertebrates and invertebrates.
Compressive syndrome of internal jugular veins in multiple sclerosis: does it matter?
Authors: Radak Dj , Tanaskovic S , Antonic Z , Kolar J , Aleksic N , Ilijevski N
Published: September 2012

Objectives

Condition known as chronic cerebrospinal venous insufficiency (CCSVI) is characterized by insufficient cerebral vein drainage in patients with multiple sclerosis (MS) and internal jugular vein (IJV), vertebral and/or azygos veins stenoses. However, external compression on the IJV was not clearly described as a potential cause of CCSVI. We aim to present a case of CCSVI in a patient with MS caused by bilateral IJV inverted valves combined with IJV external compression by carotid bulb.

Methods

A 31-year-old female patient was admitted to our institute for IJV and vertebral veins morphological and haemodynamical assessment after being treated for MS for the last 14 years. Colour Doppler ultrasonography showed right IJV prestenotic dilation and inverted valves in both IJV. Computerized tomography angiography showed bilateral IJV compression by carotid bulb. Haemodynamical Doppler parameters showed that external IJV compression significantly contributed to CCSVI occurrence.

Results

Bilateral IJV confluence percutaneous angioplasty (PTA) was done, and the patient was discharged for further neurological examination. Partial carbon dioxide pressure was significantly lower in the distal part of both IJV following PTA and oxygen saturation increased.

Conclusion

In the case presented, PTA of the IJV confluence resulted in haemodynamic improvement despite the presence of IJV external compression.
Teaching Students to be Innovators: Examining Competencies and Approaches Across Disciplines
Authors: Duval-Couetil Nathalie , Dyrenfurth Michael
Published: September 2012

Universities are increasingly promoting programs and courses that focus on innovation to prepare students across disciplines for work in a competitive global economy. Information about program outcomes, target competencies, or best practices is limited given their early stages of development. This exploratory study examined eight academic programs offering an educational credential focused on innovation available to students in a variety of majors. The analyses of program descriptions and curricular requirements provide an understanding of their structure, content, and value they propose to students. This paper explores what teaching innovation means at a program-level and identifies where a curriculum is situated along the spectrum of topics that characterize innovation education. The results can be useful in developing and articulating core competencies related to innovation and understanding approaches to teaching it.
Learning from Aviation to Improve Safety in the Operating Room ‐ a Systematic Literature Review
Authors: Wauben Linda S. G. L. , Lange Johan F. , Goossens Richard H. M.
Published: September 2012

Lessons learned from other high‐risk industries could improve patient safety in the operating room (OR). This review describes similarities and differences between high‐risk industries and describes current methods and solutions within a system approach to reduce errors in the OR. PubMed and Scopus databases were systematically searched for relevant articles written in the English language published between 2000 and 2011. In total, 25 articles were included, all within the medical domain focusing on the comparison between surgery and aviation. In order to improve safety in the OR, multiple interventions have to be implemented. Additionally, the healthcare organization has to become a ‘learning organization’ and the OR team has to become a team with shared responsibilities and flat hierarchies. Interpersonal and technical skills can be trained by means of simulation and can be supported by implementing team briefings, debriefings and cross‐checks. However, further development and research is needed to prove if these solutions are useful, practical, and actually increase safety.