bluuebunny/crossref_metadata_2025 huggingface dataset:
PROVENGE (Sipuleucel-T) in Prostate Cancer: The First FDA-Approved Therapeutic Cancer Vaccine
Authors: Cheever Martin A. , Higano Celestia S.
Published: April 2011

Sipuleucel-T (PROVENGE; Dendreon) is the first therapeutic cancer vaccine to be approved by the U.S. Food and Drug Administration. In men who have metastatic castration-resistant prostate cancer with no or minimal symptoms, sipuleucel-T prolongs median survival by 4.1 months compared with results in those treated with placebo. At 3 years, the proportion of patients in the vaccine group who were alive was 50% higher than that in the control group (31.7% versus 21.7%, respectively). Sipuleucel-T, which is designed to elicit an immune response to prostatic acid phosphatase, uses the patient's own immune system to recognize and combat his cancer. Currently, no other agents are available that offer a survival benefit for this population of asymptomatic patients who have not been treated with chemotherapy, except for docetaxel (whose inherent toxicities often lead patients and physicians to delay administration until symptoms develop). Straightforward strategies to increase the efficacy of sipuleucel-T are likely to provide even greater benefit. The preclinical and clinical development of sipuleucel-T is reviewed, and approaches to enhance efficacy are considered herein. Clin Cancer Res; 17(11); 3520–6. ©2011 AACR.
Targeting Oncogenic ALK: A Promising Strategy for Cancer Treatment
Authors: Grande Enrique , Bolós María-Victoria , Arriola Edurne
Published: April 2011

Recently, the anaplastic lymphoma kinase (ALK) has been found to be altered in several solid and hematologic tumors. Novel drugs targeting this tyrosine kinase receptor are under development, and early clinical trials are showing promising activity in non–small cell lung cancer patients with ALK+ tumors. Here, we review the structure and function of the ALK receptor, the mechanisms associated with its deregulation in cancer, methods for ALK detection in tumor samples, its potential as a new marker for candidate patient selection for tailored therapy, and novel drugs under development that target ALK. Mol Cancer Ther; 10(4); 569–79. ©2011 AACR.
Pathway Analysis of Glioblastoma Tissue after Preoperative Treatment with the EGFR Tyrosine Kinase Inhibitor Gefitinib—A Phase II Trial
Authors: Hegi Monika E. , Diserens Annie-Claire , Bady Pierre , Kamoshima Yuta , Kouwenhoven Mathilde C. M. , Delorenzi Mauro , Lambiv Wanyu L. , Hamou Marie-France , Matter Matthias S. , Koch Arend , Heppner Frank L. , Yonekawa Yasuhiro , Merlo Adrian , Frei Karl , Mariani Luigi , Hofer Silvia
Published: April 2011

Amplification of the epidermal growth factor receptor (EGFR) gene is one of the most common oncogenic alterations in glioblastoma (45%) making it a prime target for therapy. However, small molecule inhibitors of the EGFR tyrosine kinase showed disappointing efficacy in clinical trials for glioblastoma. Here we aimed at investigating the molecular effects of the tyrosine kinase inhibitor gefitinib on the EGFR signaling pathway in human glioblastoma. Twenty-two patients selected for reoperation of recurrent glioblastoma were treated within a phase II trial for 5 days with 500 mg gefitinib before surgery followed by postoperative gefitinib until recurrence. Resected glioblastoma tissues exhibited high concentrations of gefitinib (median, 4.1 μg/g), 20 times higher than respective plasma. EGFR-pathway activity was evaluated with phosphorylation-specific assays. The EGFR was efficiently dephosphorylated in treated patients as compared to a control cohort of 12 patients. However, no significant effect on 12 pathway constituents was detected. In contrast, in vitro treatment of a glioblastoma cell line, BS-153, with endogenous EGFRwt amplification and EGFRvIII expression resulted not only in dephosphorylation of the EGFR, but also of key regulators in the pathway such as AKT. Treating established xenografts of the same cell line as an in vivo model showed dephosphorylation of the EGFR without affecting downstream signal transductors, similar to the human glioblastoma. Taken together, gefitinib reaches high concentrations in the tumor tissue and efficiently dephosphorylates its target. However, regulation of downstream signal transducers in the EGFR pathway seems to be dominated by regulatory circuits independent of EGFR phosphorylation. Mol Cancer Ther; 10(6); 1102–12. ©2011 AACR.
Differential Roles for the Interferon-Inducible IFI16 and AIM2 Innate Immune Sensors for Cytosolic DNA in Cellular Senescence of Human Fibroblasts
Authors: Duan Xin , Ponomareva Larissa , Veeranki Sudhakar , Panchanathan Ravichandran , Dickerson Eric , Choubey Divaker
Published: April 2011

The IFN-inducible IFI16 and AIM2 proteins act as innate immune sensors for cytosolic double-stranded DNA (dsDNA). On sensing dsDNA, the IFI16 protein induces the expression of IFN-β whereas the AIM2 protein forms an inflammasome, which promotes the secretion of IL-1β. Given that the knockdown of IFI16 expression in human diploid fibroblasts (HDF) delays the onset of cellular senescence, we investigated the potential roles for the IFI16 and AIM2 proteins in cellular senescence. We found that increased IFI16 protein levels in old (vs. young) HDFs were associated with the induction of IFN-β. In contrast, increased levels of the AIM2 protein in the senescent (vs. old) HDFs were associated with increased production of IL-1β. The knockdown of type I IFN-α receptor subunit, which reduced the basal levels of the IFI16 but not of the AIM2, protein delayed the onset of cellular senescence. Accordingly, increased constitutive levels of IFI16 and AIM2 proteins in ataxia telangiectasia mutated (ATM) HDFs were associated with the activation of the IFN signaling and increased levels of IL-1β. The IFN-β treatment of the young HDFs, which induced the expression of IFI16 and AIM2 proteins, activated a DNA damage response and also increased basal levels of IL-1β. Interestingly, the knockdown of AIM2 expression in HDFs increased the basal levels of IFI16 protein and activated the IFN signaling. In contrast, the knockdown of the IFI16 expression in HDFs decreased the basal and dsDNA-induced activation of the IFN signaling. Collectively, our observations show differential roles for the IFI16 and AIM2 proteins in cellular senescence and associated secretory phenotype. Mol Cancer Res; 9(5); 589–602. ©2011 AACR.
Levels of Surfactant Proteins A and D and KL-6 Are Elevated in the Induced Sputum of Chronic Obstructive Pulmonary Disease Patients: A Sequential Sputum Analysis
Authors: Ishikawa Nobuhisa , Hattori Noboru , Tanaka Sonosuke , Horimasu Yasushi , Haruta Yoshinori , Yokoyama Akihito , Kohno Nobuoki , Kinnula Vuokko L.
Published: April 2011

Background: Recent clinical studies have suggested that serum surfactant protein (SP) A, SP-D and Krebs von den Lungen-6 (KL-6) are potential biomarkers for interstitial lung diseases. Serum levels of SP-A and SP-D have also been found to be elevated in chronic obstructive pulmonary disease (COPD), but their significance has not been evaluated or compared in induced sputum samples obtained directly from the airways. Objective: A sequential sputum analysis was conducted to assess the value of SP-A, SP-D and KL-6 levels in COPD. Methods: The study material consisted of induced sputum samples from 61 subjects, 28 with COPD and 33 with prolonged cough (cough lasting >3 weeks and normal spirometry). Sputum was collected in 3 fractions (3 periods of 5 min each). Sputum levels of these proteins were measured, and receiver operating characteristic curve analysis was carried out to evaluate the sensitivity, specificity and area under the curve (AUC) for each fraction. Results: The levels of SP-A, SP-D and KL-6 were higher in patients with COPD than in those with prolonged cough in each of the fractions. Sputum levels of these proteins correlated inversely with obstruction and positively with ageing, smoking history, sputum macrophages and eosinophils. Sputum fractionation had a relatively minor effect on the levels and AUC of these proteins. Conclusion: Sequential sputum analysis from 3 consecutive fractions indicated a significant difference in the levels of SP-A, SP-D and KL-6 between COPD and prolonged cough. However, sputum fractionation itself had a relatively minor effect on the levels of these proteins.
Activation of the Prefrontal Cortex Is Associated with Exertional Dyspnea in Chronic Obstructive Pulmonary Disease
Authors: Higashimoto Yuji , Honda Noritsugu , Yamagata Toshiyuki , Matsuoka Toshiki , Maeda Kazushige , Satoh Rhyuji , Nishiyama Osamu , Sano Hiroyuki , Iwanaga Takashi , Miyara Takayuki , Muraki Masato , Tomita Katsuyuki , Kume Hiroaki , Miyai Ichiro , Tohda Yuji , Fukuda Kanji
Published: April 2011

Background: Exertional dyspnea is the primary symptom that limits exercise in patients with chronic obstructive pulmonary disease (COPD). It is unknown which activated brain area is associated with this symptom in COPD patients. Objectives: To investigate the activation of cortical areas associated with dyspnea during exercise in COPD patients. Methods: COPD patients (n = 10) and age-matched controls (n = 10) performed mild-intensity constant work rate cycle exercise (40% of their symptom-limited peak work rates) for 10 min, while cerebral hemodynamics and oxygenation were measured by near-infrared spectroscopy (NIRS). Ventilatory responses (breathing pattern and pulmonary gas exchange) and Borg scale ratings of dyspnea and leg fatigue were measured during exercise. Three NIRS probes were placed over the prefrontal and temporoparietal cortical regions of the subjects’ heads. Changes in cortical oxyhemoglobin (oxy-Hb), deoxyhemoglobin (deoxy-Hb), and total hemoglobin (total Hb) concentrations from baseline recordings were measured. Increased oxy-Hb (oxygenation) was assumed to reflect cortical activation. Results: Oxy-Hb concentration was significantly increased in the prefrontal region during exercise in both groups but not in the temporoparietal regions. The change in prefrontal oxy-Hb concentration of COPD patients was not different from that of controls. Dyspnea scores were positively correlated with changes in oxy-Hb concentrations of the prefrontal regions in both groups. Multivariate analysis showed that oxy-Hb concentration in the prefrontal region was the best predictor of dyspnea in both groups. Conclusions: Exertional dyspnea was related to activation (oxygenation) of the prefrontal cortex in COPD patients and control subjects.
Disseminated Strongyloides stercoralis Infection in HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma
Authors: Stewart Donn M. , Ramanathan Roshan , Mahanty Siddhartha , Fedorko Daniel P. , Janik John E. , Morris John C.
Published: April 2011

A 55-year-old woman with human T-cell lymphotropic virus type-1 (HTLV-1)-associated adult T-cell leukemia (ATL) and a history of previously treated Strongyloides stercoralis infection received anti-CD52 monoclonal antibody therapy with alemtuzumab on a clinical trial. After an initial response, she developed ocular involvement by ATL. Alemtuzumab was stopped and high-dose corticosteroid therapy was started to palliate her ocular symptoms. Ten days later, the patient developed diarrhea, vomiting, fever, cough, skin rash, and a deteriorating mental status. She was diagnosed with disseminated S. stercoralis. Corticosteroids were discontinued and the patient received anthelmintic therapy with ivermectin and albendazole with complete clinical recovery.
Measuring Therapeutic Efficacy in Patients with Alzheimer’s Disease: Role of Instruments
Authors: Riepe Matthias W. , Janetzky Wolfgang , Lemming Ole M.
Published: April 2011

Background/Aims: Global cognitive scales and meta-analyses thereof are used to appraise therapeutic efficacy over a broad range of disease severity. Clinically, however, different aspects of cognition change in different stages of disease. Methods: Calculation of effect sizes for single cognitive functions on treatment as assessed by the Alzheimer’s Disease Assessment Scale (ADAS-cog), the Mini-Mental-Status Examination (MMSE), and the Severe Impairment Battery (SIB). In these scales, subdomains of ‘cognition’, e.g. memory and language, are represented in different proportions. To exemplify the analysis of ‘cognition’, we used original data of previously published clinical studies with memantine. Results: Depending on dementia severity and on the scale used, the effect size for memory varies between –0.44 and +0.34 and for language between –0.40 and +0.26. Conclusion: Beyond interstudy variance, effect sizes for treatment with antidementia drugs are subject to disease stage, instruments used, and interaction thereof. Therefore, clinical interpretation is necessary to appraise therapeutic efficacy in clinical studies and meta-analyses thereof when patients with different severity are included or different instruments are used. Alternatively, severity-adapted endpoints should be used for appraisal and meta-analysis of therapeutic efficacy.
Different Effect of IgA Nephropathy and Polycystic Kidney Disease on Arterial Stiffness
Authors: Késői István , Sági Balázs , Tóth Orsolya I. , Vas Tibor , Fazekas Attila , Kovács Tibor , Pintér Tünde , Wittmann István , Nagy Judit
Published: April 2011

Background: Renal function is a major predictor of vascular function and cardiovascular diseases. Little information exists about the effect of specific renal diseases on vascular function in chronic kidney diseases (CKD). Methods: One hundred and twenty patients (60 with IgA nephropathy, IgAN, and 60 with polycystic kidney disease, PKD) with CKD stages 1–4 were studied and compared. Pulse-wave velocity was measured by the digital volume pulse (DVP) method and stiffness index (SIDVP) was derived. Results: All CKD (IgAN and PKD) patients had increased SIDVP compared to controls (10.39 vs. 8.87 ± 1.79 m/s, p = 0.008). PKD patients had increased SIDVP compared to IgAN and controls (11.14 ± 2.19, 9.66 ± 2.02 and 8.87 ± 1.79 m/s, respectively, p < 0.001). An inverse correlation was found between SIDVP and glomerular filtration rate in all CKD (IgAN and PKD) patients (p = 0.001) and in IgAN alone (p < 0.01), but not in PKD. With multivariate regression analysis, only age and 24-hour systolic blood pressure exerted independent effects on SIDVP. Conclusions: Compared to controls, arterial stiffness was increased in CKD patients. However, arterial stiffening was more pronounced in PKD than in IgAN, suggesting that vascular function is not similarly altered in etiologically different CKD groups. The fact that blood pressure was an independent risk factor underscores a therapeutic opportunity.
Asymptotic Properties of an Autocorrelation Coefficient for Coherent Doppler Sonar
Authors: Dillon Jeremy , Zedel Len , Hay Alex E.
Published: April 2011

A new formula is derived for the asymptotic form of the magnitude of an autocorrelation coefficient for coherent Doppler sonar. The autocorrelation magnitude is shown to be a biased estimator in the limit of infinite ensemble length. Numerical simulation of a Gaussian random process is used to verify the asymptotic formula and to show that a bias persists for finite pulse-pair averages. Validity of the asymptotic formula is also confirmed using a high-fidelity coherent Doppler sonar simulation, and from sonar measurements in a towing tank. It is shown that the distribution of observed autocorrelation coefficients is well predicted by a Gaussian random process once the autocorrelation bias has been removed.
A Scale-Invariant Formulation of the Anticipated Potential Vorticity Method
Authors: Chen Qingshan , Gunzburger Max , Ringler Todd
Published: April 2011

The long-term success of climate models that operate on multiresolution grids depends on access to subgrid parameterizations that act appropriately across a wide range of spatial and temporal scales. As the first step in a series of efforts to obtain such scale-aware subgrid parameterizations, the authors focus on the anticipated potential vorticity method (APVM) on a sequence of quasi-uniform grids with varying resolutions. Through a scale analysis technique and phenomenological theories for two-dimensional turbulent flows, they derive a new formulation of the APVM that depends on a single parameter that is formally independent of the time-step size, the grid resolution, and the flow itself. Results of numerical experiments with this new formulation demonstrate that the optimal parameter of the new APVM formulation is invariant with respect to the time-step size, is insensitive to the flows, and is only weakly dependent on the grid resolution.
Operational Convective-Scale Numerical Weather Prediction with the COSMO Model: Description and Sensitivities
Authors: Baldauf Michael , Seifert Axel , Förstner Jochen , Majewski Detlev , Raschendorfer Matthias , Reinhardt Thorsten
Published: April 2011

Since April 2007, the numerical weather prediction model, COSMO (Consortium for Small Scale Modelling), has been used operationally in a convection-permitting configuration, named COSMO-DE, at the Deutscher Wetterdienst (DWD; German weather service). Here the authors discuss the model changes that were necessary for the convective scale, and report on the experience from the first years of operational application of the model. For COSMO-DE the ability of the numerical solver to treat small-scale structures has been improved by using a Runge–Kutta method, which allows for the use of higher-order upwind advection schemes. The one-moment cloud microphysics parameterization has been extended by a graupel class, and adaptations for describing evaporation of rain and stratiform precipitation processes were made. Comparisons with a much more sophisticated two-moment scheme showed only minor differences in most cases with the exception of strong squall-line situations. Whereas the deep convection parameterization was switched off completely, small-scale shallow convection was still parameterized by the appropriate part of the Tiedtke scheme. During the first year of operational use, convective events in synoptically driven situations were satisfactorily simulated. Also the daily cycles of summertime 10-m wind and 1-h precipitation sums were well captured. However, it became evident that the boundary layer description had to be adapted to enhance convection initiation in airmass convection situations. Here the asymptotic Blackadar length scale l∞ had proven to be a sensitive parameter.
Computerized Texture Analysis of Carotid Plaque Ultrasonic Images Can Identify Unstable Plaques Associated With Ipsilateral Neurological Symptoms
Authors: Kakkos Stavros K. , Nicolaides Andrew N. , Kyriacou Efthyvoulos , Daskalopoulou Stella S. , Sabetai Michael M. , Pattichis Constantinos S. , Geroulakos George , Griffin Maura B. , Thomas Dafydd
Published: April 2011

We estimated the value of objective, computerized texture analysis of ultrasonic images in distinguishing carotid plaques associated with neurological ipsilateral symptoms (amaurosis fugax [AmF; n = 30], transient ischemic attack [TIA; n = 52], and stroke [n = 55]) from asymptomatic plaques (n = 51). We performed 3 case-control studies (1/symptom with asymptomatic plaques as control). On logistic regression, AmF was independently associated with severity of stenosis, percentage of pixels with gray levels 0 to 10 (PPCS1; measure of echolucency), and spatial gray level dependence matrices (SGLDM) information measure of correlation (IMC-1; texture); TIAs with PPCS1 (echolucency), SGLDM correlation, and skewness (both texture); and stroke with PPCS1, SGLDM correlation, and percentage of pixels with gray levels 11 to 20 (PPCS2; echolucency). The area under the curve of the regression-derived predicted probability for AmF, TIA, and stroke was 0.92, 0.82, and 0.85, respectively (all P < .001). Texture analysis can identify carotid plaques associated with a neurological event, improving the diagnostic value of echolucency measures. Texture analyses could be applied to natural history studies.
Early Identification of Vascular Damage in Patients With Systemic Sclerosis
Authors: Cusmà Piccione Maurizio , Bagnato Gianluca , Zito Concetta , Di Bella Gianluca , Caliri Annalisa , Catalano Mariarita , Longordo Caterina , Oreto Giuseppe , Bagnato Gianfilippo , Carerj Scipione
Published: April 2011

Vascular involvement in systemic sclerosis (SSc) plays a key role in the pathogenesis of fibrosis. We assessed arterial stiffness using a new echo-tracking technique in patients with SSc asymptomatic for cardiovascular diseases. We enrolled 22 patients (21 female, 63 ± 14 years) and 20 controls (12 female, 62 ± 3 years). Carotid intima-media thickness (IMT) was comparable between the 2 groups (1.1 ± 0.3 vs 1.0 ± 0.4 mm, P = ns), whereas the stiffness parameters were significantly increased in patients (β: 9.5 ± 4.2 vs 5.8 ± 1.1, P = .001; pulse wave velocity [PWV]: 6.5 ± 1.5 vs 5.2 ± 0.6 m/sec, P = .003). A correlation between stiffness parameters, anti-Scl-70 antibodies (β: r = .46, P = .03; PWV: r = .50, P = .02), and anticentromere antibodies (β: r = -.54, P = .020; PWV: r = -.53, P = .023) was found. Echo-tracking technique may be valuable in early identification of vascular involvement in patients with SSc.
A Simple Scoring System to Improve Clinical Assessment of Acute Otitis Media
Authors: Casey Janet R. , Block Stan , Puthoor Pamela , Hedrick Jim , Almudevar Anthony , Pichichero Michael E.
Published: April 2011

Objective. To evaluate an easy to use 10-point scoring system in clinical assessment of acute otitis media (AOM). Study design. Symptoms of AOM observed by validated otoscopists were tabulated and scored with a 10-point and a 30-point system at acute onset of illness and at the test-of-cure (TOC) 3 weeks later. Results. A total of 330 children (mean age = 13.1 months) with AOM were studied. At AOM onset, the mean 10-point and 30-point scores; were highly correlated ( P < .001). At TOC, 256 children were cured, 69 failed, and 5 were lost to follow-up. The 10-point scores were 0.5 and 4.4 for children with cure and failure. The 10-point score had a sensitivity of 87%, specificity of 98%, positive predictive value of 91%, and negative predictive value of 97% compared with the diagnosis by validated otoscopists. Conclusion. A simple, easy-to-use 10-point AOM scoring system was shown to discriminate AOM cure and failure at TOC.
Mode I delamination growth of multidirectional composite laminates under fatigue loading
Authors: Lei Peng  , Jianyu Zhang  , Libin Zhao  , Rui Bao  , Hongqin Yang  , Binjun Fei
Published: April 2011

Fatigue delamination growth of multidirectional carbon/bismaleimide composites was investigated to disclose the specific role of ply orientations. Both fatigue crack growth rate and threshold values of strain energy release rate in Mode I were studied by double cantilever beam test. For specimens with rising delamination resistance effect, the fatigue crack growth rate was found to be dependent on normalized interlaminar energy, GI/GIC, rather than GI. The experimental data also show that the fatigue threshold Gth is almost proportional to the corresponding GIC, that is Gth /GIC is constant and hardly affected by the midplane-adjacent fiber orientation. Furthermore, fractographs revealed that the rising delamination resistance is dominantly aroused by fiber bridging and intra-ply fracture.
Limitation of Economic Damages as a ‘Humanitarian Gesture’: The German Foundation ‘Remembrance, Responsibility and the Future’
Authors: Hense Anja
Published: April 2011

Over 50 years after the end of the second world war, the German foundation ‘Remembrance, Responsibility and the Future’ was established in order to guarantee a collective compensation of victims of slave and forced labour and ‘aryanization’ in the nazi era. The Foundation was frequently praised as a final sign of the historical and moral responsibility of the German state and economy for ‘nazi wrongs’. Some survivors’ organizations and other participants of the international negotiations on the compensation settlement, in contrast, judged the Foundation as a late and hard-won compromise, which had little relation to the unpaid wages and the misery and repression suffered.

In order to evaluate the Foundation as an element of the German compensation politics towards victims of National Socialism, it is necessary to take a close look at its genesis and conception. This article therefore explores which factors determined the international negotiations on a collective compensation settlement for former slave and forced labourers at the end of the twentieth century, and to what extent the survivors’ claims for recognition of the crimes committed, and a comprehensive and adequate compensation were realized. It will be shown that the Foundation was not the result of a voluntary and ‘humanitarian’ initiative of the German economy and government and that numerous victims’ groups were excluded from the modest payments made to especially harshly damaged survivors.
Popular Film-going in Britain in the Early 1930s
Authors: James Robert
Published: April 2011

This article examines the relationship between leisure and class in early 1930s Britain. Based on an examination of Sidney Bernstein’s film popularity surveys, the article offers a comparative analysis of the tastes of middle- and working-class cinema-goers in a period during which society’s engagement with that cultural medium was vital. It argues that while the middle and working classes shared many similarities in film tastes, they also exhibited a number of key differences. These differences, it is claimed, were directly linked to their class position. While gender, generation and geographical location are all shown to be determining factors in the consumption process, it is argued that class was the principal determinant overall.
The Air Panic of 1935: British Press Opinion between Disarmament and Rearmament
Authors: Holman Brett
Published: April 2011

The British fear of bombing in the early twentieth century has aptly been termed ‘the shadow of the bomber’. But the processes by which the public learned about the danger of bombing are poorly understood. This paper proposes that the press was the primary source of information about the threat, and examines a formative period in the evolution of public concern about airpower — the so-called air panic of 1935 — during which German rearmament was revealed and large-scale RAF expansion undertaken in response. A proposed air pact between the Locarno powers enabled a shift from support of disarmament to rearmament by newspapers on the right, while simultaneously supporting collective security. Paradoxically, after initially supporting the air pact, the left-wing press and its readers began to have doubts, for the same reason: the need to support collective security. This episode sheds new light on Britain’s early rearmament, and how the government was able to undertake it, despite the widespread feelings in the electorate in favour of disarmament.
Parents and Children in Second World War Germany: An Inter-generational Perspective on Wartime Separation
Authors: Vaizey Hester
Published: April 2011

This article discusses how the relationship between parents and their children were affected by the second world war in Germany. With fathers away from home for often as long as a decade, many children grew up without a father being physically present. The current historiography suggests that wartime separation caused a crisis in the family. But did the prolonged periods of time apart and the separate experiences of husbands at the Front and wives and children at home really destabilize family relationships? This article questions such a picture of families in ruin. It argues that family relationships were far more resilient in the face of wartime separation than has previously been credited. Indeed, it reveals the importance of children in keeping mothers and fathers focused on getting through the war. It further contends that, even from afar, fathers continued to play an important role in their children’s lives. And this in turn revises our understanding of the situation facing reuniting families.
Host-Pathogen Interactions in Progressive Chronic Periodontitis
Authors: Hernández M. , Dutzan N. , García-Sesnich J. , Abusleme L. , Dezerega A. , Silva N. , González F.E. , Vernal R. , Sorsa T. , Gamonal J.
Published: April 2011

Periodontitis is an infection characterized by the occurrence of supporting tissue destruction with an episodic nature. Disease progression is often determined by the loss of attachment level or alveolar bone, and sequential probing of periodontal attachment remains the most commonly utilized method to diagnose progressive destruction of the periodontium. The tolerance method has been the most extensive clinical method used in recent years to determine site-specific attachment level changes. There is abundant evidence that major tissue destruction in periodontal lesions results from the recruitment of immune cells. Considerable effort has been made to study the host cell and mediator profiles involved in the pathogenesis of chronic periodontitis, but the definition of active sites, where current periodontal breakdown occurs, and consecutive characterization of the mediators involved are still among the main concerns. In the present review, we summarize periodontopathic bacteria and host factors, including infiltrating cell populations, cytokines, and host matrix metalloproteinases, associated with under-going episodic attachment loss that could partly explain the mechanisms involved in destruction of the supporting tissues of the tooth.
Cytolethal Distending Toxin Damages the Oral Epithelium of Gingival Explants
Authors: Damek-Poprawa M. , Haris M. , Volgina A. , Korostoff J. , DiRienzo J.M.
Published: April 2011

The cytolethal distending toxin (Cdt), expressed by the periodontal pathogen Aggregatibacter actinomycetemcomitans, inhibits the proliferation of cultured epithelial cells by arresting the cell cycle. The gingival epithelium is an early line of defense against microbial assault. When damaged, bacteria collectively gain entry into underlying connective tissue where microbial products can affect infiltrating inflammatory cells, leading to the destruction of the attachment apparatus. Histological evaluation of rat and healthy human gingival tissue exposed ex vivo to the Cdt for 36 and 18 hours, respectively, revealed extensive detachment of the keratinized outer layer and distention of spinous and basal cells in the oral epithelium. Treated human tissue also exhibited disruption of rete pegs and dissolution of cell junctions. Cells in the connective tissue appeared unaffected. Primary gingival epithelial cells, but not gingival fibroblasts, isolated from the same healthy human tissue were cell-cycle-arrested when treated with the toxin. These findings provide new evidence that the Cdt severely damages the oral epithelium, ex vivo, by specifically targeting epithelial cells, in situ. The Cdt shows preferential targeting of the epithelium as opposed to connective tissue in animal and human gingival explant models.

Abbreviations: cytolethal distending toxin (Cdt), connective tissue (CT), 4′,6-diamidino-2-phenylindole (DAPI), human gingival epithelial cells (HGEC), human gingival explants (HGX), human gingival fibroblasts (HGF), junctional epithelium (JE), oral epithelium (OE), rete pegs (RP), sulcular epithelium (SE)
Apoptotic Genes are Differentially Expressed in Aged Gingival Tissue
Authors: González O.A. , Stromberg A.J. , Huggins P.M. , Gonzalez-Martinez J. , Novak M.J. , Ebersole J.L.
Published: April 2011

Cellular and molecular changes of the periodontium associated with a higher prevalence of oral diseases (e.g., chronic periodontitis) in aged populations have received little attention. Since impaired apoptosis during aging appears to be related to chronic inflammatory disorders, we hypothesized that the expression of genes associated with apoptotic processes are altered in aged healthy and periodontitis-affected gingival tissue. Ontology analysis of 88 genes related to apoptotic pathways was performed in gingival biopsies of healthy and periodontitis sites from young, adult, and aged non-human primates (Macaca mulatta), using the GeneChip® Rhesus Macaque Genome Array. Lower expression of anti-apoptotic and higher expression of pro-apoptotic genes were associated with healthy gingival tissue from young compared with aged animals. Few differences in gene expression were observed in healthy gingival tissue between adult and aged animals. Comparison between healthy and periodontitis gingival tissues showed that the up- or down-regulated apoptotic genes in diseased gingival tissue are different in adults compared with aged animals. These results suggest that apoptotic events normally occurring in gingival tissues could be reduced in aging,and unique aspects of apoptotic pathways are potentially involved in the pathophysiology of perio-dontal disease in adult vs. aged gingival tissues.
Camus’s Challenge
Authors: O’Dwyer Kathleen
Published: April 2011

In the opening essay of The Myth of Sisyphus and Other Essays, Camus states that: “There is but one truly serious philosophical problem, and that is suicide. Judging whether life is or is not worth living amounts to answering the fundamental question of philosophy.” He argues that all the other questions of philosophy, dealing with truth, knowledge, ethics, science, language and so on, are necessarily secondary to this question: “I therefore conclude that the meaning of life is the most urgent of questions.” The meaning of life —why am I here? how am I to live? what is my purpose?—is one of the most enduring questions in philosophy and psychology and it is a question confronted by almost every individual at some point in life. This article provides a contemporary reflection on the relevance and validity of Camus’s thought regarding the connection between suicide and the meaning of life.
Assessing the Robustness of Crisp-set and Fuzzy-set QCA Results
Authors: Skaaning Svend-Erik
Published: April 2011

Configurational comparative methods constitute promising methodological tools that narrow the gap between variable-oriented and case-oriented research. Their infancy, however, means that the limits and advantages of these techniques are not clear. Tests on the sensitivity of qualitative comparative analysis (QCA) results have been sparse in previous empirical studies, and so has the provision of guidelines for doing this. Therefore this article uses data from a textbook example to discuss and illustrate various robustness checks of results based on the employment of crisp-set QCA and fuzzy-set QCA. In doing so, it focuses on three issues: the calibration of raw data into set-membership values, the frequency of cases linked to the configurations, and the choice of consistency thresholds. The study emphasizes that robustness tests, using systematic procedures, should be regarded as an important, and maybe even indispensable, analytical step in configurational comparative analysis.
Primer on Pramlintide, an Amylin Analog
Authors: Traina Andrea N. , Kane Michael P.
Published: April 2011

Purpose

Pramlintide is an injectable synthetic analog of human amylin. It is indicated for patients with type 1 or type 2 diabetes who are taking mealtime insulin but have been unable to achieve desired glucose targets. Pramlintide decreases postprandial glucose by lowering inappropriate postmeal glucagon secretion, slowing gastric emptying, and increasing satiety. As such, pramlintide targets several of the defects commonly seen in patients with diabetes. Given the unique characteristics of this agent in the treatment of diabetes, a practical guide to its use is presented.

Conclusion

Pramlintide treats diabetes with a novel mechanism of action, offering the potential for improved postprandial control and weight loss for patients with type 1 or type 2 diabetes. Providers and diabetes educators should be familiar with the utility of the medication as well as its potential limitations in order to fully educate patients and maximize treatment options for patients with diabetes.
Perils and Profits
Authors: Madsen Peter M.
Published: April 2011

In many industries, for-profit business organizations make decisions that critically impact the safety of their employees and the public. Managers in such organizations often argue that there is no trade-off between profitability and safety because “safety is good business.” However, prior studies examining the profitability–safety relationship report inconsistent and conflicting results. In the present study, the author reexamines this issue, building on insights into managerial risk taking from the behavioral theory of the firm and hypothesizing that the slope of the profitability–safety relationship reaches an inflection point at the organizational profitability aspiration. Using data from the U.S. airline industry, the author finds support for this hypothesis, with results indicating a positive association between airline profitability and airline accident rates for airlines performing below their aspirations but a negative association for airlines performing above their aspirations.
Using visual support for language and learning in children with SLCN: A training programme for teachers and teaching assistants
Authors: Wellington Wendy , Stackhouse Joy
Published: April 2011

The majority of children with speech, language and communication needs (SLCN) are educated in mainstream classrooms where they can have difficulties with the language needed for learning. Although visual support in the classroom can help to scaffold children’s learning and socialization, many teachers feel ill equipped to use this. They do not feel confident enough to identify, differentiate and support children with SLCN. This article presents a training and mentoring programme delivered to teachers and teaching assistants (TAs) in seven mainstream primary schools. It involved a group training session outlining the nature and identification of children with SLCN, impact of SLCN on accessing the curriculum, and visual strategies and techniques for supporting learning. This was followed up by six, weekly mentoring sessions in the classroom with a speech and language therapist (SLT) or SLT assistant (SLTA). Pre- and post-training questionnaires and classroom observations were used to examine the impact of this programme. The observations were repeated after one school term to establish if the use of visual support had been maintained. Although there were differences between the teachers and TAs pre-training, they both increased their use of visual support strategies in the classroom post-training and maintained this one term after the training had ceased. The method and practical implications of this study are discussed.
Consequence of Preterm Birth in Early Adolescence: The Role of Language on Auditory Short-term Memory
Authors: Fraello David , Maller-Kesselman Jill , Vohr Betty , Katz Karol H. , Kesler Shelli , Schneider Karen , Reiss Allan , Ment Laura , Spann Marisa N.
Published: April 2011

This study tested the hypothesis that preterm early adolescents’ short-term memory is compromised when presented with increasingly complex verbal information and that associated neuroanatomical volumes would differ between preterm and term groups. Forty-nine preterm and 20 term subjects were evaluated at age 12 years with neuropsychological measures and magnetic resonance imaging (MRI). There were no differences between groups in simple short-term and working memory. Preterm subjects performed lower on learning and short-term memory tests that included increased verbal complexity. They had reduced right parietal, left temporal, and right temporal white matter volumes and greater bilateral frontal gray and right frontal white matter volumes. There was a positive association between complex working memory and the left hippocampus and frontal white matter in term subjects. While not correlated, memory scores and volumes of cortical regions known to subserve language and memory were reduced in preterm subjects. This study provides evidence of possible mechanisms for learning problems in former preterm infants.
Unusual Spinal Cord Lesions in Late-Onset Non-ketotic Hyperglycinemia
Authors: Wei Shu-Hao , Weng Wen-Chin , Lee Ni-Chung , Hwu Wu-Lian , Lee Wang-Tso
Published: April 2011

Non-ketotic hyperglycinemia is a disorder of glycine metabolism with severe neurologic regression in the infantile stage, while late-onset non-ketotic hyperglycinemia is a rare form characterized by variable clinical, biochemical, and imaging features. This report describes a boy of late-onset non-ketotic hyperglycinemia presenting with an unusual long tract-like lesion of the spinal cord aside by magnetic resonance imaging. This is the first reported child of non-ketotic hyperglycinemia with abnormal imaging features of spinal cord.
Synthesis and chemical curing kinetics of epoxy resin containing α,β-unsaturated carbonyl moiety in the main chain
Authors: Balakrishnan P. Shanmugaraj , Balaji Krishnasamy , Murugavel Salem Chandrasekaran
Published: April 2011

A new epoxy resin containing an α,β-unsaturated carbonyl group in the main chain was synthesized by solution polycondensation of 3-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl) propenone with epichlorohydrin. The synthesized epoxy resin was characterized systematically by Fourier transform infrared, 1H- and 13C-nuclear magnetic resonance spectroscopic techniques. The thermogravimetric analysis data revealed that the resin was stable up to 320 °C. Differential scanning calorimetry was used to analyze the curing kinetics of the epoxy resin. The activation energy for the curing of the resin was estimated using both Arrhenius and Kissinger methods and the values obtained were 156 and 142 kJ mol−1, respectively.
Creating a Safe Environment for Women’s Leadership Transformation
Authors: Debebe Gelaye
Published: April 2011

This study used qualitative data to describe how transformational learning was achieved in a women-only training (WOT) program. The article argues that an environment conducive to transformational learning for women was created from the harmonious coalescing of the presence of all-women participants and instructors with gender-sensitive teaching and learning practices. The integration of these elements created safety and participant willingness to break with habitual patterns. This article contributes to the transformational learning and WOT literatures by proposing a holistic explanation for creating safety and fostering women’s transformational learning in training settings. It also develops an analytic framework that expands current conceptions of the transformational learning process.
Renal Cell Carcinoma in Children and Young Adults: Clinicopathological, Immunohistochemical, and VHL Gene Analysis of 46 Cases With Follow-up
Authors: Qiu Rao  , Chen Jie-yu , Wang Jian-dong , Ma Heng-hui , Zhou Hang-bo , Lu Zhen-feng , Zhou Xiao-jun
Published: April 2011

To further study the characteristics of renal cell carcinoma (RCC) in young patients and better define their biological features, 46 RCCs of patients younger than 25 years were morphologically and immunohistochemically characterized with follow-up. Loss of heterozygosity (LOH) analysis of the von Hippel—Lindau (VHL) gene region and screening for VHL gene mutations were performed in all tumors. Applying the 2004 WHO classification for RCC, there were 19 Xp11.2 translocation RCCs, 9 clear cell RCCs, 17 papillary RCCs, and 1 unclassified RCC. All 19 Xp11.2 translocation RCCs showed moderate to strong immunoreactivity for TFE3. None had TFEB immunoreactivity. One Xp11.2 translocation RCC had an unreported morphology with empty or ground glass nuclei, occasional nuclear grooves, inconspicuous nucleoli and abundant mucinous material in stroma.VHL gene analysis revealed deletions at 3p25-26 in 1 clear cell RCC and 1 papillary type 2 RCC. The papillary type 2 RCC was also presented with a family history of VHL disease and found a germline mutation G → C on a splicing site at position 553+5. The present case widens the spectrum of microscopic features to be found in VHL-associated RCC. There were no VHL mutations in the remaining 45 RCCs. Statistical analysis of stage and outcome revealed that TFE+ pediatric RCCs were significantly more frequently associated with a higher pTNM pT3/pT4 stage and a poorer outcome than TFE-RCCs ( P < .05). Owing to the already known aggressive behavior of these Xp11.2 translocation RCCs, patients with TFE+ pediatric RCCs should benefit from a stricter follow-up.
Myopericytoma: A Pleural-Based Spindle Cell Neoplasm Off the Beaten Path
Authors: Edgecombe Allison , Peterson Rebecca A. , Shamji Farid M. , Commons Susan , Sekhon Harman , Gomes Marcio M.
Published: April 2011

Myopericytoma is a recently described hemangiopericytoma-like neoplasm with myoid differentiation. These tumors are typically located in the subcutaneous and soft tissues of the extremities. The authors report a rare pleural-based pulmonary myopericytoma in a 58-year-old woman. The lesion was grossly homogeneous and well circumscribed. Microscopically, it was composed of densely packed spindle cells organized as whorls and short interlacing fascicles with a concentric perivascular distribution. Immunohistochemical reactions were positive for vimentin, smooth muscle actin (SMA), muscle-specific actin, and Bcl-2 and negative for desmin, h-caldesmon, cytokeratin, and CD34. Atypically, increased mitotic activity was noted, but no other malignant features were identified. The differential diagnoses are discussed with specific emphasis on solitary fibrous tumor of the pleura, which is the most common benign pleural-based spindle cell neoplasm and may be a diagnostic pitfall with potentially harmful consequences.
Colonization of Intestinal Endometriosis by Benign Colonic Mucosa: A Pattern Potentially Misdiagnosed as Invasive Mucinous Carcinoma
Authors: Ponsford Tipps Ann M. , Weidner Noel
Published: April 2011

Endometriosis is well known for creating diagnostic pitfalls for pathologists. It may produce masses mimicking neoplasms or cause diagnostic quandaries, particularly when the patient age, location, and/or epithelial appearance are atypical. This study reports a patient with endometriosis causing rectal bleeding and involving the cecum. It produced a mass clinically considered appendiceal. The endometriosis was focally lined by intestinal epithelium including Paneth cells. In the deep endometriotic glands embedded within intestinal wall, direct fusion of the intestinal and the endometrial epithelium—the benign intestinal epithelium apparently colonizing the endometriotic foci—was found. The mass effect, plus deep-seated intestinal epithelium, closely mimicked invasive well-differentiated mucinous carcinoma. This is yet another peculiar presentation of endometriosis with potential for misinterpretation as a more serious condition, specifically well-differentiated mucinous carcinoma of the cecum or appendix.
Chasing a Myth? Searching for ‘Self’ Through Lifestyle Travel
Authors: Cohen Scott A.
Published: April 2011

This paper problematizes the concept of searching for self in the context of lifestyle travellers — individuals for whom extended leisure travel is a preferred lifestyle that they return to repeatedly. Qualitative findings on the search for self from in-depth semi-structured interviews with lifestyle travellers in northern India and southern Thailand are considered in light of opposing academic perspectives on self. The study reveals a theoretical tension that exists between lifestyle travellers who may seek a unified sense of self, underpinned by the essentialist position that one’s ‘true self’ exists, and contrasting widely held academic viewpoints that instead conceptualize embodied selves as relational and open to multiple performances.