bluuebunny/crossref_metadata_2025 huggingface dataset:
Giving Voice From the Perspectives of African American Women Leaders
Authors: Stanley Christine A.
Published: November 2009

The problem and the solution. This Issue overview introduces the problem, purpose, significance, and need for studying leadership from the perspectives of African American women. The concept of intersectionality is introduced and is a common thread throughout the articles contained in this Issue. The need for more sociocultural theories in the field of human resource development (HRD) that address intersectionality in the leadership experience is the overarching theme of this Issue. A discussion of the contribution to HRD is provided in this overview as well as a preview of each article contained in this Issue.
Bringing the Voices Together
Authors: Byrd Marilyn Y. , Stanley Christine A.
Published: November 2009

The linking pin among the articles in this Issue is the existence of sociocultural realities of race, gender, and social class in the everyday, lived experiences of African American women leaders. Sociocultural realities make an argument for recognizing intersectionality (the juncture of these sociocultural realities) and the experiences that can emerge (disempowering, exclusion, etc.). Therefore, sociocultural theories are needed to explain these experiences. The overarching theme of this Issue has been to give voice to African American women on encounters with intersectionality in their leadership experience. Until the silent voices are allowed to speak, the dominant perspectives will continue to ignore and challenge the need for these conversations to take place. It is in making the space for and the hearing of these voices that the value to HRD lies. For doing so informs the development and refinement of informing HRD theories, the expansion of the theoretical foundations of HRD, and the more informed research and practice of the field and profession.
Implications of Race and Gender in Higher Education Administration: An African American Woman’s Perspective
Authors: Lloyd-Jones Brenda
Published: November 2009

A qualitative single-case-study approach is used in this study to examine the lived experiences of an African American woman senior-level administrator in a predominantly White research university. The everyday, lived experience of the participant challenges the ideology that education and hard work are combinations that equal success. The findings in the study indicate that despite achieving advanced levels of education and holding high-ranking positions within academia, many African American women in administrative positions encounter social inequity emerging from intersectionality. The dichotomous tension between achievement ideologies, as “the great equalizer,” and the organizational structure as a form of resistance to social equity are continuous threads throughout this article.
Borrowed Power
Authors: Petitt Becky
Published: November 2009

Whiteness is a critical issue in organizational culture and power. Because White individuals define, control, and shape organizational realities, policies, and practices, people of color—African American women, in the present example—are never fully empowered. The power African American women hold is borrowed power; it can be taken away at any moment. In this article, the author discusses the sociocultural realities of her experience as an African American woman working in a predominately White institution of higher education and provides illustrations of the impermanence of her authority under the weight of whiteness. Recommendations are made for advancing HRD theory by drawing from nontraditional theoretical frameworks for explaining the realities of African American women in positions of leadership.
From The Simpsons to “The Simpsons of the South Pacific”: New Zealand’s First Primetime Animation, bro’Town
Authors: Lustyik Katalin , Smith Philippa
Published: November 2009

New Zealand’s first primetime animated program, bro’Town, ran successfully for five seasons between 2004 and 2009. Described by its creators as a “modern-day non-PC satire,” bro’Town focuses on five New Zealand teenagers of Samoan and Maori ethnicities growing up in Auckland. While the program was promoted as “ The Simpsons of the South Pacific,” its audience, critics, and politicians have celebrated it as a twenty-first-century New Zealand creative success story. This article explores the historical, cultural, and economic forces that have shaped bro’Town in the context of the debates on media globalization using the framework of hybridity as “the cultural logic of globalization” as well as the framework of global television formats. The authors suggest that bro’Town represents a complex case of television program adaptation and provides a unique case study to examine the multilayered nature of contemporary hybrid cultural forms moving beyond the simplistic local—global dyad.
Interleukin-6 is essential for zwitterionic polysaccharide-mediated abscess formation
Authors: Meemboor Sonja , Mertens Janina , Flenner Eva , Groneck Laura , Zingarelli Alessandra , Gamstätter Thomas , Bessler Martina , Seeger Jens M. , Kashkar Hamid , Odenthal Margarete , Kalka-Moll Wiltrud Maria
Published: November 2009

Abscess formation associated with secondary peritonitis causes severe morbidity and can be fatal. Formation of abscesses requires the presence of CD4+ T-cells. Zwitterionic polysaccharides (ZPSs) represent a novel class of immunomodulatory bacterial antigens that stimulate CD4+ T-cells in a major histocompatibility complex (MHC) class II-dependent manner. The capsular polysaccharide Sp1 of Streptococcus pneumoniae serotype 1 possesses a zwitterionic charge with free amino groups and promotes T-cell-dependent abscess formation in an experimental mouse model. So far, nothing is known about the function of Interleukin (IL)-6 in intraperitoneal abscess formation. Here, we demonstrate that macrophages and dendritic cells (DCs), the most prevalent professional antigen-presenting cells involved in the formation of abscesses, secrete Interleukin (IL)-6 and are incorporated in the abscess capsule. Sp1 inhibits apoptosis of CD4 + T-cells and causes IL-17 expression by CD4+ T-cells in an IL-6-dependent manner. Abrogation of the Sp1-induced pleiotropic effects of IL-6 in IL-6-deficient mice and mice treated with an IL-6-specific neutralizing antibody results in significant inhibition of abscess formation. The data delineate the essential role of IL-6 in the linkage of innate and adaptive immunity in polysaccharide-mediated abscess formation.
Role of beta-adrenergic receptor blocking agents in hypertensive diseases: personal thoughts as the controversy persists
Authors: Frohlich Edward D.
Published: November 2009

The long history of the beta-adrenergic receptor blockers for the treatment of hypertension is fraught with many controversies. The first compound had severe untoward effects preventing their use until propranolol was introduced. It was found effective for treatment of angina pectoris since not all patients with hypertension responded to monotherapy with a meaningful reduction of pressure. Nevertheless, the beta-blockers were most effective in: younger patients, especially with hyperkinetic circulation; with co-morbid diseases (e.g. coronary arterial disease with or without prior myocardial infarction); or when used with a diuretic. Subsequently with the advent of meta-analysis to evaluate more generalized experience, controversy resumed with statements made to exclude beta-blockers for initial hypertensive therapy. Support for this argument was gained with reports of patients developing ‘dysglycemia’ with treatment. However, exclusion of any one therapeutic class for a multifactorial disease such as hypertension seems unrealistic. Meta-analysis confounded this conclusion since inadequate numbers of patients having specific clinical and biological characteristics were included (especially young patients). This is particularly important at this time when third-party reimbursement procedures are particularly relevant and when the primary care physician must deal with the individual patient. The NICE report has introduced specific thinking along these lines. In-and-of itself, its recommendations are reasonable, but current articles continue to suggest that the ‘older’ beta-blockers should be excluded from national guidelines for initial antihypertensive therapy. Personally, I disagree; and, no doubt, controversy will continue.
Scarf Osteotomy for the Correction of Adolescent Hallux Valgus
Authors: John Shine , Weil Lowell , Weil Lowell Scott , Chase Kari
Published: November 2009

Adolescent hallux valgus deformity is a complex surgical condition. Although several techniques have been described to correct this deformity in adults, limitations exist for adolescents because of the presence of open growth plates and high recurrence rates. This retrospective study reports results of 7 patients (14 feet) using the Scarf osteotomy for correction of adolescent hallux valgus deformity. All patients underwent concomitant bilateral hallux valgus surgery. Radiographic evaluation measures included intermetatarsal 1-2 angle, hallux valgus angle, and distal metatarsal articular angle. Data recorded from the lateral radiograph evaluated the first metatarsal declination angle. Postoperative patient satisfaction was assessed using a standard patient satisfaction survey. Postoperative, subjective, and objective measurements were calculated using the American College of Foot and Ankle Surgeons (ACFAS) Scoring Scale for the First Metatarsophalangeal Joint and First Ray and the American Orthopaedic Foot & Ankle Society (AOFAS) Hallux Metatarsophalangeal-Interphalangeal Scoring Scale. Average patient age and follow-up were 14.43 years and 57 months, respectively. There was 100% maternal inheritance of hallux valgus deformity. The average postoperative ACFAS Metatarsophalangeal Joint and First Ray Scale (module 1) score was 94.72, and the average AOFAS Hallux Metatarsophalangeal-Interphalangeal Scale score was 96.43. Complications included 1 patient who underwent revision surgery on 1 foot 18 years after the date of index surgery because of painful recurrence of the deformity. The authors believe the Scarf osteotomy is a safe, effective, and versatile procedure for the correction of juvenile and adolescent hallux valgus deformity.
CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets
Authors: Yu Jianhua , Mao Hsiaoyin C. , Wei Min , Hughes Tiffany , Zhang Jianying , Park Il-kyoo , Liu Shujun , McClory Susan , Marcucci Guido , Trotta Rossana , Caligiuri Michael A.
Published: November 2009

Human CD56bright natural killer (NK) cells possess little or no killer immunoglobulin-like receptors (KIRs), high interferon-γ (IFN-γ) production, but little cytotoxicity. CD56dim NK cells have high KIR expression, produce little IFN-γ, yet display high cytotoxicity. We hypothesized that, if human NK maturation progresses from a CD56bright to a CD56dim phenotype, an intermediary NK cell must exist, which demonstrates more functional overlap than these 2 subsets, and we used CD94 expression to test our hypothesis. CD94highCD56dim NK cells express CD62L, CD2, and KIR at levels between CD56bright and CD94lowCD56dim NK cells. CD94highCD56dim NK cells produce less monokine-induced IFN-γ than CD56bright NK cells but much more than CD94lowCD56dim NK cells because of differential interleukin-12–mediated STAT4 phosphorylation. CD94highCD56dim NK cells possess a higher level of granzyme B and perforin expression and CD94-mediated redirected killing than CD56bright NK cells but lower than CD94lowCD56dim NK cells. Collectively, our data suggest that the density of CD94 surface expression on CD56dim NK cells identifies a functional and likely developmental intermediary between CD56bright and CD94lowCD56dim NK cells. This supports the notion that, in vivo, human CD56bright NK cells progress through a continuum of differentiation that ends with a CD94lowCD56dim phenotype.
Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant Vα14-Jα18 TCRα gene
Authors: Watarai Hiroshi , Rybouchkin Andrei , Hongo Naomi , Nagata Yuko , Sakata Sakura , Sekine Etsuko , Dashtsoodol Nyambayar , Tashiro Takuya , Fujii Shin-ichiro , Shimizu Kanako , Mori Kenji , Masuda Kyoko , Kawamoto Hiroshi , Koseki Haruhiko , Taniguchi Masaru
Published: November 2009

Establishment of a system with efficient generation of natural killer T (NKT) cells from embryonic stem (ES) cells would enable us to identify the cells with NKT-cell potential and obtain NKT cells with desired function. Here, using cloned ES (NKT-ES) cells generated by the transfer of nuclei from mature NKT cells, we have established a culture system that preferentially developed functional NKT cells and also identified early NKT progenitors, which first appeared on day 11 as a c-kit+ population in the cocultures on OP9 cells with expression of Notch ligand, delta-like1 (OP9/Dll-1) and became c-kitlo/− on day 14. Interestingly, in the presence of Notch signals, NKT-ES cells differentiated only to thymic CD44lo CD24hi NKT cells producing mainly interleukin-4 (IL-4), whereas NKT cells resembling CD44hi CD24lo liver NKT cells producing mainly interferon γ (IFN-γ) and exhibiting strong adjuvant activity in vivo were developed in the switch culture starting at day 14 in the absence of Notch. The cloned ES culture system offers a new opportunity for the elucidation of the molecular events on NKT-cell development and for the establishment of NKT-cell therapy.
Three-dimensional migration of macrophages requires Hck for podosome organization and extracellular matrix proteolysis
Authors: Cougoule Céline , Le Cabec Véronique , Poincloux Renaud , Al Saati Talal , Mège Jean-Louis , Tabouret Guillaume , Lowell Clifford A. , Laviolette-Malirat Nathalie , Maridonneau-Parini Isabelle
Published: November 2009

Tissue infiltration of phagocytes exacerbates several human pathologies including chronic inflammations or cancers. However, the mechanisms involved in macrophage migration through interstitial tissues are poorly understood. We investigated the role of Hck, a Src-family kinase involved in the organization of matrix adhesion and degradation structures called podosomes. In Hck−/− mice submitted to peritonitis, we found that macrophages accumulated in interstitial tissues and barely reached the peritoneal cavity. In vitro, 3-dimensional (3D) migration and matrix degradation abilities, 2 protease-dependent properties of bone marrow–derived macrophages (BMDMs), were affected in Hck−/− BMDMs. These macrophages formed few and undersized podosome rosettes and, consequently, had reduced matrix proteolysis operating underneath despite normal expression and activity of matrix metalloproteases. Finally, in fibroblasts unable to infiltrate matrix, ectopic expression of Hck provided the gain–of–3D migration function, which correlated positively with formation of podosome rosettes. In conclusion, spatial organization of podosomes as large rosettes, proteolytic degradation of extracellular matrix, and 3D migration appeared to be functionally linked and regulated by Hck in macrophages. Hck, as the first protein combining a phagocyte-limited expression with a role in 3D migration, could be a target for new anti-inflammatory and antitumor molecules.
Purified T-depleted, CD34+ peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia
Authors: Sodani Pietro , Isgrò Antonella , Gaziev Javid , Polchi Paola , Paciaroni Katia , Marziali Marco , Simone Maria Domenica , Roveda Andrea , Montuoro Aldo , Alfieri Cecilia , De Angelis Gioia , Gallucci Cristiano , Erer Buket , Isacchi Giancarlo , Zinno Francesco , Adorno Gaspare , Lanti Alessandro , Faulkner Lawrence , Testi Manuela , Andreani Marco , Lucarelli Guido
Published: November 2009

Fetomaternal microchimerism suggests immunological tolerance between mother and fetus. Thus, we performed primary hematopoietic stem cell transplantation from a mismatched mother to thalassemic patient without an human leukocyte antigen–identical donor. Twenty-two patients with thalassemia major were conditioned with 60 mg/kg hydroxyurea and 3 mg/kg azathioprine from day −59 to −11; 30 mg/m2 fludarabine from day −17 to −11; 14 mg/kg busulfan starting on day −10; and 200 mg/kg cyclophosphamide, 10 mg/kg thiotepa, and 12.5 mg/kg antithymocyte globulin daily from day −5 to −2. Fourteen patients received CD34+-mobilized peripheral blood and bone marrow progenitor cells; 8 patients received marrow graft–selected peripheral blood stem cells CD34+ and bone marrow CD3/CD19-depleted cells. T-cell dose was adjusted to 2 × 105/kg by fresh marrow cell addback at the time of transplantation. Both groups received cyclosporine for graft-versus-host disease prophylaxis for 2 months after transplantation. Two patients died (cerebral Epstein-Barr virus lymphoma or cytomegalovirus pneumonia), 6 patients reject their grafts, and 14 showed full chimerism with functioning grafts at a median follow-up of 40 months. None of the 14 patients who showed full chimerism developed acute or chronic graft-versus-host disease. These results suggest that maternal haploidentical hematopoietic stem cell transplantation is feasible in patients with thalassemia who lack a matched related donor.
A population-based cytogenetic study of adults with acute lymphoblastic leukemia
Authors: Moorman Anthony V. , Chilton Lucy , Wilkinson Jennifer , Ensor Hannah M. , Bown Nick , Proctor Stephen J.
Published: November 2009

Chromosomal abnormalities are increasingly used to risk stratify adults with acute lymphoblastic leukemia. Published data describing the age-specific incidence of chromosomal abnormalities and their prognostic relevance are largely derived from clinical trials. Trials frequently have age restrictions and low recruitment rates. Thus we investigated these factors in a population-based cohort of 349 patients diagnosed during the course of 19 years in the northern part of England. The incidence of most chromosomal abnormalities varied significantly with age. The incidence of t(9;22)(q34;q11) increased in each successive decade, up to 24% among 40- to 49-year-old subjects. Thereafter the incidence reached a plateau. t(4;11)(q21;q23) and t(1;19)(q23;p13) were a rare occurrence among patients older than 60 years of age. In contrast, the frequency of t(8;14)(q24;q32) and t(14;18)(q32;q21) increased with age. High hyperdiploidy occurred in 13% of patients younger than 20 years of age but in only 5% of older patients. The incidence of low hypodiploidy/near-triploidy and complex karyotype increased with age from 4% (15-29 years) to 16% (≥ 60 years). Overall survival varied significantly by age and cytogenetics. Older patients and those with t(9;22), t(4;11), low hypodiploidy/near-triploidy, or complex karyotype had a significantly inferior outcome. These population-based results demonstrate the cytogenetic heterogeneity of adult acute lymphoblastic leukemia. These data will inform the delivery of routine clinical services and the design of new age-focused clinical trials.
Differential genome-wide array–based methylation profiles in prognostic subsets of chronic lymphocytic leukemia
Authors: Kanduri Meena , Cahill Nicola , Göransson Hanna , Enström Camilla , Ryan Fergus , Isaksson Anders , Rosenquist Richard
Published: November 2009

Global hypomethylation and regional hypermethylation are well-known epigenetic features of cancer; however, in chronic lymphocytic leukemia (CLL), studies on genome-wide epigenetic modifications are limited. Here, we analyzed the global methylation profiles in CLL, by applying high-resolution methylation microarrays (27 578 CpG sites) to 23 CLL samples, belonging to the immunoglobulin heavy-chain variable (IGHV) mutated (favorable) and IGHV unmutated/IGHV3-21 (poor-prognostic) subsets. Overall, results demonstrated significant differences in methylation patterns between these subgroups. Specifically, in IGHV unmutated CLL, we identified methylation of 7 known or candidate tumor suppressor genes (eg, VHL, ABI3, and IGSF4) as well as 8 unmethylated genes involved in cell proliferation and tumor progression (eg, ADORA3 and PRF1 enhancing the nuclear factor-κB and mitogen-activated protein kinase pathways, respectively). In contrast, these latter genes were silenced by methylation in IGHV mutated patients. The array data were validated for selected genes using methylation-specific polymerase chain reaction, quantitative reverse transcriptase–polymerase chain reaction, and bisulfite sequencing. Finally, the significance of DNA methylation in regulating gene promoters was shown by reinducing 4 methylated tumor suppressor genes (eg, VHL and ABI3) in IGHV unmutated samples using the methyl-inhibitor 5-aza-2′-deoxycytidine. Taken together, our data for the first time reveal differences in global methylation profiles between prognostic subsets of CLL, which may unfold epigenetic silencing mechanisms involved in CLL pathogenesis.
Endothelin-1 receptor antagonists prevent the development of pulmonary emphysema in rats
Authors: Chen Y. , Hanaoka M. , Droma Y. , Chen P. , Voelkel N. F. , Kubo K.
Published: November 2009

We hypothesised that endothelin (ET)-1 plays an important role in the pathogenesis of emphysema. We attempted to apply ET-1 receptor antagonists to demonstrate and further elucidate the molecular pathogenesis pathways through which ET-1 may cause emphysematous changes.

Sprague-Dawley rats were divided into four groups: control, cigarette smoke extract (CSE), CSE+BQ-123 (a selective endothelin receptor type A (ETA) antagonist) and CSE+bosentan (a mixed ETA/ETBreceptor antagonist). The CSE was injected intraperitoneally once a week for 3 weeks, and BQ-123 or bosentan was administered daily for the same duration. The expression of ETAreceptor, apoptosis index, caspase-3 activity, matrix metalloproteinase (MMP)-2 and MMP-9 activity, and tumour necrosis factor (TNF)-α and interleukin (IL)-1β concentrations were measured in the lung tissue. The ET-1 levels and antioxidant activity were measured in the serum.

Both BQ-123 and bosentan prevented the development of CSE-induced emphysema, blocked the expression of ETAreceptor, inhibited pulmonary apoptosis, inactivated MMP-2 and MMP-9 activities in the lung tissues, reduced the concentrations of inflammatory cytokines TNF-α and IL-1β, and improved the biological antioxidant activity in the serum.

Emphysema development is suppressed by ET-1 receptor antagonists. ET-1 may cause emphysematous changes through molecular pathogenesis pathways involving apoptosis, proteinase and antiproteinase imbalance, inflammation and oxidative stress.
Glutathione peroxidase-2 protects from allergen-induced airway inflammation in mice
Authors: Dittrich A. M. , Meyer H-A. , Krokowski M. , Quarcoo D. , Ahrens B. , Kube S. M. , Witzenrath M. , Esworthy R. S. , Chu F-F. , Hamelmann E.
Published: November 2009

The aim of the present study was to identify and validate the biological significance of new genes/proteins involved in the development of allergic airway disease in a murine asthma model.

Gene microarrays were used to identify genes with at least a two-fold increase in gene expression in lungs of two separate mouse strains with high and low allergic susceptibility. Validation of mRNA data was obtained by western blotting and immunohistochemistry, followed by functional analysis of one of the identified genes in mice with targeted disruption of specific gene expression.

Expression of two antioxidant enzymes, glutathione peroxidase-2 (GPX2) and glutathioneS-transferase omega (GSTO) 1-1 was increased in both mouse strains after induction of allergic airway disease and localised in lung epithelial cells. Mice with targeted disruption of theGpx-2gene showed significantly enhanced airway inflammation compared to sensitised and challenged wild-type mice.

Our data indicate that genes encoding the antioxidants GPX2 andGSTO 1-1are common inflammatory genes expressed upon induction of allergic airway inflammation, and independently of allergic susceptibility. Furthermore, we provide evidence to illustrate the importance of a single antioxidant enzyme, GPX2, in protection from allergen-induced disease.
Variability in the prevalence of premenstrual asthma
Authors: Pereira Vega A. , Sánchez Ramos J. L. , Maldonado Pérez J. A. , Álvarez Gutierrez F. J. , Ignacio García J. M. , Vázquez Oliva R. , Romero Palacios P. , Bravo Nieto J. M. , Sánchez Rodríguez I. , Gil Muñoz F.
Published: November 2009

Our aim is to analyse the differences in the prevalence of premenstrual asthma (PMA) according to a set of criteria, the relationship between them and the influence of asthma severity.

The answer “Yes” to “Does your asthma get worse before menstruation?” was considered subjective PMA. A daily respiratory symptoms register of fertile asthmatic females was taken during two consecutive menstrual cycles. For the semi-objective diagnosis, an exacerbation of ≥20% was required in the symptoms register. Objective diagnosis was a premenstrual worsening of ≥20% of peak flow.

We selected 103 patients. Subjective premenstrual deterioration was perceived in 43.7%. The semi-objective deterioration of symptoms in the first cycle occurred in 44.7%, and in 22.3% in both cycles. A total of 54.3% of females with semi-objective criteria in the first cycle perceived a subjective deterioration of symptoms,versus35.1% of those without semi-objective criteria (p = 0.05). PMA was present at all levels of asthma severity, with no clear link to the degree of severity.

The detection of PMA prevalence, the subjective perception of this deterioration and its presence at all levels of asthma severity lead us to urge research into possible premenstrual deterioration in all fertile asthmatic females.
Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension
Authors: Sztrymf B. , Souza R. , Bertoletti L. , Jaïs X. , Sitbon O. , Price L. C. , Simonneau G. , Humbert M.
Published: November 2009

Acute right ventricular failure in the setting of pulmonary arterial hypertension (PAH) often requires hospitalisation in intensive care units (ICU) to manage the subsequent low cardiac output and its consequences. There are very few data on these acute events.

We recorded demographic, clinical and biological data and therapy in consecutive patients suffering from acute right heart failure requiring catecholamine treatment in the ICU of the French referral centre for pulmonary hypertension. These variables were analysed according to the survival status in ICU.

46 patients were included, the mean age was 50.3 yrs. ICU mortality was 41%. We found no difference in terms of demographics, clinical data, last haemodynamic measurements at admission. Systemic arterial pressure was significantly lower in the subgroup of patients whose clinical course was fatal. Plasma brain natriuretic peptide (BNP), C-reactive protein (CRP), serum sodium and creatinine at admission correlated with survival. Demonstration of an infection during the ICU stay was associated with a worse prognosis.

These preliminary results underline the importance of some simple clinical and biological parameters in the prognostic evaluation of acute heart failure in the setting of PAH. Whether these parameters can guide therapy needs to be further investigated.
Negative impacts of unreported COPD exacerbations on health-related quality of life at 1 year
Authors: Xu W. , Collet J-P. , Shapiro S. , Lin Y. , Yang T. , Wang C. , Bourbeau J.
Published: November 2009

Unreported chronic obstructive pulmonary disease (COPD) exacerbations are common, but their intermediate-to-long-term impacts on health-related quality of life (HRQoL) are unknown. The aim of the present study was to examine the impact of unreported exacerbations on HRQoL at 1 yr.

A multicentric prospective cohort study in 491 COPD patients was conducted in China. HRQoL was measured using the St George's Respiratory Questionnaire (SGRQ). Other measurements included sociodemographic, clinical, psychosocial and treatment profiles. Patients were monitored monthly for 12 months to document exacerbations (at least one symptom worsening for ≥48 h). Patients were categorised into six groups: no exacerbation, one unreported exacerbation only, more than one unreported exacerbation only, one reported exacerbation only, more than one reported exacerbation only, and both unreported and reported exacerbations. Generalised estimating equations were used to estimate the adjusted associations between exacerbations and HRQoL change.

A total of 466 unreported and 410 reported exacerbations were recorded. Compared with patients with no exacerbations, the change in SGRQ total score was similar amongst patients with one unreported exacerbation (adjusted mean change 1.22 points (95% CI -4.05–6.48)), but significantly worse among patients with more than one unreported exacerbation (4.61 (95% CI 0.09–9.13)).

Development and evaluation of self-management programmes emphasising early recognition of exacerbations and consequent action appear to be warranted.
Development and validation of the Capacity of Daily Living during the Morning questionnaire and the Global Chest Symptoms Questionnaire in COPD
Authors: Partridge M.R. , Miravitlles M. , Ståhl E. , Karlsson N. , Svensson K. , Welte T.
Published: November 2009

This report concerns the development and validation of two patient-reported outcomes questionnaires developed to assess chronic obstructive pulmonary disease (COPD) patients’ ability to perform morning activities and to evaluate their morning symptoms.

Based on interviews with COPD patients, the Capacity of Daily Living during the Morning (CDLM) questionnaire and the Global Chest Symptoms Questionnaire (GCSQ) were developed, linguistically validated and incorporated into two multicentre, randomised trials involving a total of 1,100 COPD patients; those trials were registered at ClinicalTrials.gov (NCT00496470andNCT00542880) . Data from these trials were used to determine the reliability, validity and responsiveness of the questionnaires and to derive estimates of minimal important differences (MIDs).

Both questionnaires displayed good-to-high reliability (Cronbach’s α 0.75–0.93). Analysis of convergent validity showed that CDLM and GCSQ scores correlated significantly (p<0.001) with symptoms, health-related quality of life (HRQoL) and use of rescue medication. In both trials, CDLM and GCSQ scores discriminated between patients with different levels of HRQoL, as assessed by the St George's Respiratory Questionnaire for COPD patients (SGRQ-C), but not with disease severity, as assessed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. A significant improvement in CDLM and GCSQ scores occurred in response to treatment. Estimations of MID scores, corresponding to an SGRQ-C MID of 4, were 0.20 for the CDLM questionnaire and 0.15 for the GCSQ.

Both the CDLM questionnaire and the GCSQ are easy-to-use, reliable, responsive, self-administered questionnaires that report on patients' symptoms and ability to perform morning activities.
Prevalence of sarcoidosis in Switzerland is associated with environmental factors
Authors: Deubelbeiss U. , Gemperli A. , Schindler C. , Baty F. , Brutsche M. H.
Published: November 2009

The current study aimed to investigate incidence, prevalence and regional distribution of sarcoidosis in Switzerland with respect to environmental exposures.

All sarcoidosis patients hospitalised between 2002 and 2005 were identified from the Swiss hospital statistics from the Swiss Federal Office for Statistics (Neuchâtel, Switzerland). Regional exposure characteristics included the regional distribution of different industrial sectors, agriculture and air quality. Co-inertia analysis, as well as a generalised linear model, was applied.

The prevalence of “ever-in-life” diagnosed sarcoidosis, currently active sarcoidosis and sarcoidosis requiring hospitalisation was 121 (95% CI 93–149), 44 (95% CI 34–54) and 16 (95% CI 10–22) per 100,000 inhabitants, respectively. The mean annual incidence of sarcoidosis was 7 (95% CI 5–11) per 100,000 inhabitants. The regional workforce in the metal industry, water supply, air transport factories and the area of potato production, artificial meadows (grassland) and bread grains were positively associated with the frequency of sarcoidosis.

The prevalence of sarcoidosis was higher than assumed based on former international estimates. Higher frequency was found in regions with metal industry and intense agriculture, especially production of potatoes, bread grains and artificial meadows.
Performance of optimized McRAPD in identification of 9 yeast species frequently isolated from patient samples: potential for automation
Authors: Trtkova Jitka , Pavlicek Petr , Ruskova Lenka , Hamal Petr , Koukalova Dagmar , Raclavsky Vladislav
Published: November 2009

Background

Rapid, easy, economical and accurate species identification of yeasts isolated from clinical samples remains an important challenge for routine microbiological laboratories, because susceptibility to antifungal agents, probability to develop resistance and ability to cause disease vary in different species. To overcome the drawbacks of the currently available techniques we have recently proposed an innovative approach to yeast species identification based on RAPD genotyping and termed McRAPD (Melting curve of RAPD). Here we have evaluated its performance on a broader spectrum of clinically relevant yeast species and also examined the potential of automated and semi-automated interpretation of McRAPD data for yeast species identification.

Results

A simple fully automated algorithm based on normalized melting data identified 80% of the isolates correctly. When this algorithm was supplemented by semi-automated matching of decisive peaks in first derivative plots, 87% of the isolates were identified correctly. However, a computer-aided visual matching of derivative plots showed the best performance with average 98.3% of the accurately identified isolates, almost matching the 99.4% performance of traditional RAPD fingerprinting.

Conclusion

Since McRAPD technique omits gel electrophoresis and can be performed in a rapid, economical and convenient way, we believe that it can find its place in routine identification of medically important yeasts in advanced diagnostic laboratories that are able to adopt this technique. It can also serve as a broad-range high-throughput technique for epidemiological surveillance.
Efficacy and tolerability of intravenous methylergonovine in migraine female patients attending the emergency department: a pilot open-label study
Authors: Niño-Maldonado Alfredo I , Caballero-García Gary , Mercado-Bochero Wilfrido , Rico-Villademoros Fernando , Calandre Elena P
Published: November 2009

Background

Methylergonovine is an ergot alkaloid widely used in postpartum women. It is also an active metabolite of methysergide and previous studies suggest that it could be effective against refractory headache and cluster headache. The purpose of the present study was to assess the potential therapeutic effectiveness of methylergonovine in the emergency treatment of severe migraine.

Methods

One hundred and twenty five female patients with migraine attending the emergency department received 0.15 mg of methylergonovine intravenously. Pain intensity, heart rate, blood pressure, and methylergonovine side effects were checked 5, 10, 15, 30 and 60 minutes after drug administration. An additional 0.075 mg dose of methylergonovine was administered to those patients who did not experienced relevant pain relief 15 minutes after dosing.

Results

Pain intensity decreased markedly from the first minutes after dosing, the 74.4% of patients being pain free at 60 minutes. Only seven patients required an additional dose of methylergonovine. Nausea and vomiting were the most relevant side effects related with methylergonovine administration (84% of patients). A substantial decrease (10 to 25 mmHg) in systolic blood pressure values was observed in 56% of the patients. A significant correlation (p < 0.0001) was found between the decrease in pain intensity and the reduction of systolic blood pressure.

Conclusion

Although limited by the non-controlled design of the study, our data suggest that intravenous methylergonovine can be an effective and safe drug in the management of severe migraine attacks in the emergency room.
Analysis of Factors Influencing Outcome in Patients With In-Transit Malignant Melanoma Undergoing Isolated Limb Perfusion Using Modern Treatment Parameters
Authors: Alexander H. Richard , Fraker Douglas L. , Bartlett David L. , Libutti Steven K. , Steinberg Seth M. , Soriano Perry , Beresnev Tatiana
Published: November 2009

Purpose

In-transit disease afflicts approximately 10% of patients with extremity melanoma; no single treatment approach has been uniformly accepted as the most effective. We report long-term outcomes in patients with in-transit extremity melanoma who underwent isolated limb perfusion (ILP) in an era of increasingly accurate staging, uniform operative and treatment conditions, and regular long-term follow-up.

Patients and Methods

Between May 1992 and February 2005, 91 patients (median age, 57 years; 50 women, 41 men) underwent a 90-minute hyperthermic ILP (melphalan, 10 to 13 mg/L limb volume, tumor necrosis factor [TNF; n = 44], or interferon [n = 38]) using uniform operative technique and intraoperative leak monitoring. Patients were prospectively followed for response, in-field progression-free survival (PFS), and overall survival (OS). Parameters associated with in-field PFS and OS were analyzed by standard statistical methods.

Results

There was one operative death (1.1%). There were 62 complete responses (69%) and 23 partial responses (26%) in 90 assessable patients. At a median potential follow-up of 11 years, median in-field PFS was 12.4 months and median OS was 47.4 months; 5 and 10-year actuarial OS probabilities were 43% and 34%, respectively. Female sex and low tumor burden (≤ 20 lesions) were associated with prolonged in-field PFS (male:female hazard ratio [HR], 2.07; 95% CI, 1.27 to 3.38; 21+ v ≤ 20 tumors HR, 2.29; 95% CI, 1.21 to 4.34; P < .011 for both). Female sex was associated with improved OS (P = .027; male:female HR, 1.82; 95% CI, 1.07 to 3.09).

Conclusion

In appropriately selected patients, ILP has clinical benefit. The use of TNF was not associated with improved in-field PFS, while female sex was associated with better survival.
Thyroid Hormone Induced Brown Adipose Tissue and Amelioration of Diabetes in a Patient with Extreme Insulin Resistance
Authors: Skarulis Monica C. , Celi Francesco S. , Mueller Elisabetta , Zemskova Marina , Malek Rana , Hugendubler Lynne , Cochran Craig , Solomon Jeffrey , Chen Clara , Gorden Phillip
Published: November 2009

Context: Brown adipose tissue (BAT) found by positron emission/computed tomography (PET-CT) using flouro-deoxyglucose (FDG) is inducible by cold exposure in men. Factors leading to increased BAT are of great interest for its potential role in the treatment of diabetes and obesity.

Objective: We tested whether thyroid hormone (TH) levels are related to the volume and activity of BAT in a patient with a mutation in the insulin receptor gene.

Design/Setting/Intervention: Our work was based on the case report of a patient in an observational study at the National Institutes of Health.

Patient: The patient discontinued insulin and oral antidiabetics after thyroidectomy and suppressive-dose levothyroxine therapy for thyroid cancer. PET-CT uptake in BAT was confirmed by histology and molecular analysis.

Outcomes: PET-CT studies were performed, and we measured hemoglobin A1c and resting energy expenditure before and after levothyroxine discontinuation for thyroid cancer testing. Molecular studies of BAT and white adipose samples are presented.

Result: Supraclavicular and periumbilical sc adipose tissue demonstrated molecular features of BAT including uncoupling protein-1, type 2 deiodinase, and PR domain containing 16 by quantitative PCR. Activity of type 2 deiodinase activity was increased. The discontinuation of levothyroxine resulted in decreased FDG uptake and diminished volume of BAT depots accompanied by worsening of diabetic control.

Conclusions: This case demonstrates the TH effect on BAT activity and volume in this patient and an association between BAT activity and glucose levels in this patient. Because the contribution of TH on skeletal muscle energy expenditure and fuel metabolism was not assessed, an association between BAT activity and glucose homeostasis can only be suggested.
Procurement Auctions for Differentiated Goods
Authors: Shachat Jason , Swarthout J. Todd
Published: November 2009

We consider two mechanisms to procure differentiated goods: a sealed-bid buyer-determined auction and a dynamic-bid price-based auction with bidding credits. The sealed-bid buyer-determined auction is analogous to the “request for quote” procedure commonly used by procurement agencies, and has each seller submit a price and the inherent quality of his good. Then the buyer selects the seller who offers the greatest difference in quality and price. In the dynamic-bid price-based auction with bidding credits, the buyer assigns a bidding credit to each seller conditional upon the quality of the seller's good. Then the sellers compete in an English auction, with the winner receiving the auction price and his bidding credit. Game-theoretic models predict the sealed-bid buyer-determined auction is socially efficient but the dynamic-bid price-based auction with bidding credits is not. The optimal bidding credit assignment undercompensates for quality advantages, creating a market distortion in which the buyer captures surplus at the expense of the seller's profit and social efficiency. In our experiment, the sealed-bid buyer-determined auction is less efficient than the dynamic-bid price-based auction with bidding credits. Moreover, both the buyer and seller receive more surplus in the dynamic-bid price-based auction with bidding credits.
An Interview with Ronald A. Howard
Authors: Garber Russ
Published: November 2009

Ronald A. Howard has contributed substantially to defining the field of decision analysis since his first publication using that term in 1966 (Howard 1966). He has been a professor at the School of Engineering at Stanford since 1965, currently teaching an average of 450 students per year and having had 86 Ph.D. students in the last 44 years. In addition to numerous journal publications, Ron Howard has authored five books, including one very recent book on ethical decision making (Howard 1960, 1971; Howard and Matheson 1977, 1984; Howard and Korver 2008). He earned his Sc.D. in electrical engineering from the Massachusetts Institute of Technology (MIT) in 1958. Prior to joining the Stanford faculty, Howard was associate professor of electrical engineering, associate professor of industrial management, and associate director of the Operations Research Center at MIT. In 1986 he received the Frank P. Ramsey Award for “distinguished contributions in decision analysis.” Professor Howard was also a cofounder of Strategic Decisions Group (a private consulting firm) and the Decision Education Foundation (a philanthropic educational foundation). Earlier this year I had the pleasure of interviewing Professor Howard to discuss his life and his experiences in academia and business, as well as his current directions.
Hybrid Entrepreneurship
Authors: Folta Timothy B. , Delmar Frédéric , Wennberg Karl
Published: November 2009

In contrast to previous efforts to model an individual's movement from wage work into entrepreneurship, we consider that individuals might transition incrementally by retaining their wage job while entering into self-employment. We show that these hybrid entrepreneurs represent a significant share of all entrepreneurial activity. Theoretical arguments are proposed to suggest why hybrid entrants are distinct from self-employment entrants, and why hybrid entry may facilitate subsequent entry into full self-employment. We demonstrate that there are significant theoretical and empirical consequences for this group and our understanding of self-employment entry and labor market dynamics. Using matched employee–employer data over eight years, we test the model on a population of Swedish wage earners in the knowledge-intensive sector.
Design of Decision-Making Organizations
Authors: Christensen Michael , Knudsen Thorbjørn
Published: November 2009

Starting from the premise that individuals within an organization are fallible, this paper advances the study of relationships between the organization's decision-making structure and its performance. We offer a general treatment that allows one to analyze the full range of organizational architectures between extreme centralized and decentralized forms (often referred to as hierarchies and polyarchies). Our approach furthermore allows designers to examine the change in the overall reliability of the organizational structure as the number of actors within the organization changes. We provide general proofs that show how decision-making structures can be constructed so they maximize reliability for a given number of agents. Our model can be used directly for a qualitative assessment of decision-making structures. It is thereby useful for assessment of the many complicated hybrid structures that we see in actual decision-making organizations, such as banks, purchasing departments, and military intelligence. An application from a bank illustrates how our framework can be used in practice.
Global Dual Sourcing: Tailored Base-Surge Allocation to Near- and Offshore Production
Authors: Allon Gad , Van Mieghem Jan A.
Published: November 2009

When designing a sourcing strategy in practice, a key task is to determine the average order rates placed to each source because that affects cost and supplier management. We consider a firm that has access to a responsive nearshore source (e.g., Mexico) and a low-cost offshore source (e.g., China). The firm must determine an inventory sourcing policy to satisfy random demand over time. Unfortunately, the optimal policy is too complex to allow a direct answer to our key question. Therefore, we analyze a tailored base-surge (TBS) sourcing policy that is simple, used in practice, and captures the classic trade-off between cost and responsiveness. The TBS policy combines push and pull controls by replenishing at a constant rate from the offshore source and producing at the nearshore plant only when inventory is below a target. The constant base allocation allows the offshore facility to focus on cost efficiency, whereas the nearshore facility's quick response capability is utilized only dynamically to guarantee high service. The research goals are to (i) determine the allocation of random demand into base and surge capacity, (ii) estimate corresponding working capital requirements, and (iii) identify and value the key drivers of dual sourcing. We present performance bounds on the optimal cost and prove that economic optimization brings the system into heavy traffic. We analyze the sourcing policy that is asymptotically optimal for high-volume systems and present a simple “square-root” formula that is insightful to answer our questions and sufficiently accurate for practice, as is demonstrated with a validation study.