bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients
Authors: Legge Francesco , Paglia Amelia , D'Asta Marco , Fuoco Gilda , Scambia Giovanni , Ferrandina Gabriella
Published: June 2011

Background

Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients.

Methods

Patients were administered oral celecoxib (400 mg/day) in combination with intravenous carboplatin (AUC5, q28). A Simon's two-stage design was employed.

Results

45 patients were enrolled: 23 (51.1%) presented platinum-resistance, and 27 (60%) had received at least 3 prior regimens for recurrence. The response rate was 28.9% with 3 complete and 10 partial responses (median duration of response = 6 months). Only one (0.4%) G4 non-febrile neutropenia was observed; G3 neutropenia, anemia, or thrombocytopenia, were observed in 2.5%, 1.7%, and 1.7% of the cycles, respectively. G3-4 vomiting was reported in only 1.7%, and 0.4% of the cycles were associated with G3 dyspepsia or diarrhea or constipation. Only one patient experienced G3 hypertension associated to G2 hypersensitivity reaction. No differences in baseline versus post-treatment Quality of Life scores were observed. Median progression free survival and overall survival were 5 and 13 months, respectively.

Conclusions

Celecoxib combined with carboplatin showed promising activity and it is well tolerated in heavily-treated recurrent ovarian cancer patients.

Trial registration number

NCT01124435 (ClinicalTrials.gov Identifier) and 935/03 (study ID numbers).
Improving children's nutrition environments: A survey of adoption and implementation of nutrition guidelines in recreational facilities
Authors: Olstad Dana Lee , Downs Shauna M , Raine Kim D , Berry Tanya R , McCargar Linda J
Published: June 2011

Background

Although the mandate of recreational facilities is to enhance well-being, many offer foods inconsistent with recommendations for healthy eating. Little is known regarding recreational facility food environments and how they might be improved, as few studies exist. The Alberta Nutrition Guidelines for Children and Youth (ANGCY) are intended to ensure access to healthy food choices in schools, childcare and recreational facilities. This study investigated awareness, adoption and implementation of the ANGCY among recreational facilities in Alberta, Canada, one year following their release.

Methods

A cross-sectional telephone survey was conducted from June - December, 2009 (n = 151) with managers of publicly funded recreational facilities that served food. The questionnaire included 10 closed and 7 open ended questions to assess the organizational priority for healthy eating, awareness, adoption and implementation of the ANGCY. Chi-squared tests examined quantitative variables, while qualitative data were analysed using directed content analysis. Greenhalgh's model of diffusion of complex innovations within health service organizations constituted the theoretical framework for the study.

Results

One half of respondents had heard of the ANGCY, however their knowledge of them was limited. Although 51% of facilities had made changes to improve the nutritional quality of foods offered in the past year, only a small fraction (11%) of these changes were motivated by the ANGCY. At the time of the survey, 14% of facilities had adopted the ANGCY and 6% had implemented them. Barriers to adoption and implementation were primarily related to perceived negative attributes of the ANGCY, the inner (organizational) context, and negative feedback received during the implementation process. Managers strongly perceived that implementing nutrition guidelines would limit their profit-making ability.

Conclusions

If fully adopted and implemented, the ANGCY have the potential to make a significant and sustained contribution to improving the recreational facility food environment, however one year following their release, awareness, adoption and implementation of the ANGCY remained low. A mandated policy approach could offer an efficacious, cost-effective means of improving the food environment within recreational facilities.
Static and dynamic mechanics of the murine lung after intratracheal bleomycin
Authors: Manali Effrosyni D , Moschos Charalampos , Triantafillidou Christina , Kotanidou Anastasia , Psallidas Ioannis , Karabela Sophia P , Roussos Charis , Papiris Spyridon , Armaganidis Apostolos , Stathopoulos Georgios T , Maniatis Nikolaos A
Published: June 2011

Background

Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure.

Methods

Single intratracheal injections of saline (50 μL) or bleomycin (2 mg/Kg in 50 μL saline) were administered to C57BL/6 (n = 40) and Balb/c (n = 32) mice. Injury/fibrosis score, tissue volume density (TVD), collagen content, airway resistance (R

N
), tissue damping (G) and elastance coefficient (H), hysteresivity (η), and area of pressure-volume curve (PV-A) were determined after 7 and 21 days (inflammation and fibrosis stage, respectively). Statistical hypothesis testing was performed using one-way ANOVA with LSD post hoc tests.

Results

Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and G and H non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. G and H, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, H and G was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls.

Conclusions

Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than forced oscillations at detecting inflammation and fibrosis.
Studying feasibility and effects of a two-stage nursing staff training in residential geriatric care using a 30 month mixed-methods design [ISRCTN24344776]
Authors: Betschon Elsbeth , Brach Michael , Hantikainen Virpi
Published: May 2011

Background

Transfer techniques and lifting weights often cause back pain and disorders for nurses in geriatric care. The Kinaesthetics care conception claims to be an alternative, yielding benefits for nurses as well as for clients.

Starting a multi-step research program on the effects of Kinaesthetics, we assess the feasibility of a two-stage nursing staff training and a pre-post research design. Using quantitative and qualitative success criteria, we address mobilisation from the bed to a chair and backwards, walking with aid and positioning in bed on the staff level as well as on the resident level. In addition, effect estimates should help to decide on and to prepare a controlled trial.

Methods/Design

Standard basic and advanced Kinaesthetics courses (each comprising four subsequent days and an additional counselling day during the following four months) are offered to n = 36 out of 60 nurses in a residential geriatric care home, who are in charge of 76 residents. N = 22 residents needing movement support are participating to this study.

On the staff level, measurements include focus group discussions, questionnaires, physical strain self-assessment (Borg scale), video recordings and external observation of patient assistance skills using a specialised instrument (SOPMAS). Questionnaires used on the resident level include safety, comfort, pain, and level of own participation during mobilisation. A functional mobility profile is assessed using a specialised test procedure (MOTPA).

Measurements will take place at baseline (T0), after basic training (T1), and after the advanced course (T2). Follow-up focus groups will be offered at T1 and 10 months later (T3).

Discussion

Ten criteria for feasibility success are established before the trial, assigned to resources (missing data), processes (drop-out of nurses and residents) and science (minimum effects) criteria. This will help to make rational decision on entering the next stage of the research program.

Trial Registration

Current Controlled Trials ISRCTN24344776.
MHC class I-related chain A and B ligands are differentially expressed in human cervical cancer cell lines
Authors: del Toro-Arreola Susana , Arreygue-Garcia Naela , Aguilar-Lemarroy Adriana , Cid-Arregui Angel , Jimenez-Perez Miriam , Haramati Jesse , Barros-Nuñez Patricio , Gonzalez-Ramella Oscar , del Toro-Arreola Alicia , Ortiz-Lazareno Pablo , Hernandez-Flores Georgina , Bravo-Cuellar Alejandro , Daneri-Navarro Adrian , Jave-Suarez Luis F
Published: June 2011

Background

Natural killer (NK) cells are an important resource of the innate immune system directly involved in the spontaneous recognition and lysis of virus-infected and tumor cells. An exquisite balance of inhibitory and activating receptors tightly controls the NK cell activity. At present, one of the best-characterized activating receptors is NKG2D, which promotes the NK-mediated lysis of target cells by binding to a family of cell surface ligands encoded by the MHC class I chain-related (MIC) genes, among others. The goal of this study was to describe the expression pattern of MICA and MICB at the molecular and cellular levels in human cervical cancer cell lines infected or not with human papillomavirus, as well as in a non-tumorigenic keratinocyte cell line.

Results

Here we show that MICA and MICB exhibit differential expression patterns among HPV-infected (SiHa and HeLa) and non-infected cell lines (C33-A, a tumor cell line, and HaCaT, an immortalized keratinocyte cell line). Cell surface expression of MICA was higher than cell surface expression of MICB in the HPV-positive cell lines; in contrast, HPV-negative cells expressed lower levels of MICA. Interestingly, the MICA levels observed in C33-A cells were overcome by significantly higher MICB expression. Also, all cell lines released higher amounts of soluble MICB than of soluble MICA into the cell culture supernatant, although this was most pronounced in C33-A cells. Additionally, Real-Time PCR analysis demonstrated that MICA was strongly upregulated after genotoxic stress.

Conclusions

This study provides evidence that even when MICA and MICB share a high degree of homology at both genomic and protein levels, differential regulation of their expression and cell surface appearance might be occurring in cervical cancer-derived cells.
CTX-M-14 β-lactamase-producing Citrobacter freundii isolated in Venezuela
Authors: Millán Beatriz , Ghiglione Bárbara , Díaz Tulia , Gutkind Gabriel , Araque María
Published: June 2011

A clinical isolate ofC. freundiiwith reduced susceptibility to extended-spectrum β-lactams from a woman with cystocele associated with recurrent urinary tract infection was analyzed. Susceptibility tests, double disk synergy tests (DDST) and enzymatic activity by the agar iodometric method suggested the presence of ESBLs. Conjugation experiments revealed the presence of a large conjugative plasmid (pLM07/20) with an exclusive FrepB replicon type (IncF/FIB). PCR analysis and sequencing confirmed the presence of theblaCTX-M-14gene in the pLM07/20 fromC. freundii.LM07/10. Although this is the first report of CTX-M-14 in Venezuela, we alert the medical community that future increase of these β-lactamases in our city could be due to dissemination of plasmids into bacterial populations.
Antifungal activity of redox-active benzaldehydes that target cellular antioxidation
Authors: Kim Jong H , Chan Kathleen L , Mahoney Noreen , Campbell Bruce C
Published: June 2011

Background

Disruption of cellular antioxidation systems should be an effective method for control of fungal pathogens. Such disruption can be achieved with redox-active compounds. Natural phenolic compounds can serve as potent redox cyclers that inhibit microbial growth through destabilization of cellular redox homeostasis and/or antioxidation systems. The aim of this study was to identify benzaldehydes that disrupt the fungal antioxidation system. These compounds could then function as chemosensitizing agents in concert with conventional drugs or fungicides to improve antifungal efficacy.

Methods

Benzaldehydes were tested as natural antifungal agents against strains of Aspergillus fumigatus, A. flavus, A. terreus and Penicillium expansum, fungi that are causative agents of human invasive aspergillosis and/or are mycotoxigenic. The yeast Saccharomyces cerevisiae was also used as a model system for identifying gene targets of benzaldehydes. The efficacy of screened compounds as effective chemosensitizers or as antifungal agents in formulations was tested with methods outlined by the Clinical Laboratory Standards Institute (CLSI).

Results

Several benzaldehydes are identified having potent antifungal activity. Structure-activity analysis reveals that antifungal activity increases by the presence of an ortho-hydroxyl group in the aromatic ring. Use of deletion mutants in the oxidative stress-response pathway of S. cerevisiae (sod1 Δ, sod2 Δ, glr1 Δ) and two mitogen-activated protein kinase (MAPK) mutants of A. fumigatus (sakA Δ, mpkC Δ), indicates antifungal activity of the benzaldehydes is through disruption of cellular antioxidation. Certain benzaldehydes, in combination with phenylpyrroles, overcome tolerance of A. fumigatus MAPK mutants to this agent and/or increase sensitivity of fungal pathogens to mitochondrial respiration inhibitory agents. Synergistic chemosensitization greatly lowers minimum inhibitory (MIC) or fungicidal (MFC) concentrations. Effective inhibition of fungal growth can also be achieved using combinations of these benzaldehydes.

Conclusions

Natural benzaldehydes targeting cellular antioxidation components of fungi, such as superoxide dismutases, glutathione reductase, etc., effectively inhibit fungal growth. They possess antifungal or chemosensitizing capacity to enhance efficacy of conventional antifungal agents. Chemosensitization can reduce costs, abate resistance, and alleviate negative side effects associated with current antifungal treatments.
Mutation analysis of the WNT4 gene in Han Chinese women with premature ovarian failure
Authors: Chen Beili , Suo Peisu , Wang Binbin , Wang Jing , Yang Lu , Zhou Sirui , Zhu Ying , Ma Xu , Cao Yunxia
Published: May 2011

Background

The WNT4 gene plays an important role in female sex determination and differentiation. It also contributes to maintaining of the ovaries and the survival of follicles.

Methods

We sequenced the coding region and splice sites of WNT4 in 145 Han Chinese women with premature ovarian failure (POF) and 200 healthy controls.

Results

Only one novel variation, in Exon 2 (195C > T), was detected among the women with POF. However, this synonymous variation did not result in a change in amino acid sequence (65 Asp > Asp). No further variants were found in any of the samples.

Conclusion

Although we cannot provide any evidence that it is a possible disease-causing gene, this study is the first attempt to investigate the possible role of WNT4 in Han Chinese women with POF.
Predicting streptococcal pharyngitis in adults in primary care: a systematic review of the diagnostic accuracy of symptoms and signs and validation of the Centor score
Authors: Aalbers Jolien , O'Brien Kirsty K , Chan Wai-Sun , Falk Gavin A , Teljeur Conor , Dimitrov Borislav D , Fahey Tom
Published: June 2011

Background

Stratifying patients with a sore throat into the probability of having an underlying bacterial or viral cause may be helpful in targeting antibiotic treatment. We sought to assess the diagnostic accuracy of signs and symptoms and validate a clinical prediction rule (CPR), the Centor score, for predicting group A β-haemolytic streptococcal (GABHS) pharyngitis in adults (> 14 years of age) presenting with sore throat symptoms.

Methods

A systematic literature search was performed up to July 2010. Studies that assessed the diagnostic accuracy of signs and symptoms and/or validated the Centor score were included. For the analysis of the diagnostic accuracy of signs and symptoms and the Centor score, studies were combined using a bivariate random effects model, while for the calibration analysis of the Centor score, a random effects model was used.

Results

A total of 21 studies incorporating 4,839 patients were included in the meta-analysis on diagnostic accuracy of signs and symptoms. The results were heterogeneous and suggest that individual signs and symptoms generate only small shifts in post-test probability (range positive likelihood ratio (+LR) 1.45-2.33, -LR 0.54-0.72). As a decision rule for considering antibiotic prescribing (score ≥ 3), the Centor score has reasonable specificity (0.82, 95% CI 0.72 to 0.88) and a post-test probability of 12% to 40% based on a prior prevalence of 5% to 20%. Pooled calibration shows no significant difference between the numbers of patients predicted and observed to have GABHS pharyngitis across strata of Centor score (0-1 risk ratio (RR) 0.72, 95% CI 0.49 to 1.06; 2-3 RR 0.93, 95% CI 0.73 to 1.17; 4 RR 1.14, 95% CI 0.95 to 1.37).

Conclusions

Individual signs and symptoms are not powerful enough to discriminate GABHS pharyngitis from other types of sore throat. The Centor score is a well calibrated CPR for estimating the probability of GABHS pharyngitis. The Centor score can enhance appropriate prescribing of antibiotics, but should be used with caution in low prevalence settings of GABHS pharyngitis such as primary care.
Autosomal dominant cerebellar ataxia type I: A review of the phenotypic and genotypic characteristics
Authors: Whaley Nathaniel Robb , Fujioka Shinsuke , Wszolek Zbigniew K
Published: May 2011

Type I autosomal dominant cerebellar ataxia (ADCA) is a type of spinocerebellar ataxia (SCA) characterized by ataxia with other neurological signs, including oculomotor disturbances, cognitive deficits, pyramidal and extrapyramidal dysfunction, bulbar, spinal and peripheral nervous system involvement. The global prevalence of this disease is not known. The most common type I ADCA is SCA3 followed by SCA2, SCA1, and SCA8, in descending order. Founder effects no doubt contribute to the variable prevalence between populations. Onset is usually in adulthood but cases of presentation in childhood have been reported. Clinical features vary depending on the SCA subtype but by definition include ataxia associated with other neurological manifestations. The clinical spectrum ranges from pure cerebellar signs to constellations including spinal cord and peripheral nerve disease, cognitive impairment, cerebellar or supranuclear ophthalmologic signs, psychiatric problems, and seizures. Cerebellar ataxia can affect virtually any body part causing movement abnormalities. Gait, truncal, and limb ataxia are often the most obvious cerebellar findings though nystagmus, saccadic abnormalities, and dysarthria are usually associated. To date, 21 subtypes have been identified: SCA1-SCA4, SCA8, SCA10, SCA12-SCA14, SCA15/16, SCA17-SCA23, SCA25, SCA27, SCA28 and dentatorubral pallidoluysian atrophy (DRPLA). Type I ADCA can be further divided based on the proposed pathogenetic mechanism into 3 subclasses: subclass 1 includes type I ADCA caused by CAG repeat expansions such as SCA1-SCA3, SCA17, and DRPLA, subclass 2 includes trinucleotide repeat expansions that fall outside of the protein-coding regions of the disease gene including SCA8, SCA10 and SCA12. Subclass 3 contains disorders caused by specific gene deletions, missense mutation, and nonsense mutation and includes SCA13, SCA14, SCA15/16, SCA27 and SCA28. Diagnosis is based on clinical history, physical examination, genetic molecular testing, and exclusion of other diseases. Differential diagnosis is broad and includes secondary ataxias caused by drug or toxic effects, nutritional deficiencies, endocrinopathies, infections and post-infection states, structural abnormalities, paraneoplastic conditions and certain neurodegenerative disorders. Given the autosomal dominant pattern of inheritance, genetic counseling is essential and best performed in specialized genetic clinics. There are currently no known effective treatments to modify disease progression. Care is therefore supportive. Occupational and physical therapy for gait dysfunction and speech therapy for dysarthria is essential. Prognosis is variable depending on the type of ADCA and even among kindreds.
Improved host defense against septic peritonitis in mice lacking MyD88 and TRIF is linked to a normal interferon response
Authors: Reim Daniel , Rossmann-Bloeck Tanja , Jusek Gabriela , Prazeres da Costa Olivia , Holzmann Bernhard
Published: June 2011

The signaling adapters MyD88 and TRIF are engaged by TLRs and/or receptors of the IL-1 family and are considered important for innate immune responses that combat bacterial infections. Here, the consequences of a combined MyD88 and TRIF deficiency for the innate immune response against severe septic peritonitis was examined. We demonstrate that Myd88−/−;TrifLps2/Lps2 mice had markedly reduced bacterial numbers in the peritoneal cavity and peripheral blood, indicating that bacterial clearance in this model is improved in the absence of MyD88/TRIF signals. Survival of Myd88−/−; TrifLps2/Lps2 mice was improved significantly. The lack of MyD88/TRIF signaling prevented the excessive production of inflammatory cytokines and of IL-10. In contrast, Ifng mRNA was expressed at WT levels, and induction of Ifnb mRNA was reduced only by one-half. Consistent with these findings, numerous IFN-regulated genes, including p47 and p65 GTPases, as well as CXCL10, were expressed in a MyD88/TRIF-independent manner. In support of the in vivo data, Myd88−/−; TrifLps2/Lps2 macrophages stimulated with live intestinal bacteria produced normal amounts of CXCL10. The production of p47 GTPases and CXCL10 in septic peritonitis was found to be dependent on the presence of IFNAR1, but not IFN-γ, indicating a normal induction of the type I IFN response in Myd88−/−;TrifLps2/Lps2 mice, despite attenuated IFN-β production. Together, these results provide evidence that in severe septic peritonitis, the absence of MyD88 and TRIF balances the innate immune response in a favorable manner by attenuating deleterious responses such as excessive cytokine release, while leaving intact protective IFN responses.
Suppressor of cytokine signaling (SOCS)1 is a key determinant of differential macrophage activation and function
Authors: Whyte Claire S , Bishop Eileen T , Rückerl Dominik , Gaspar-Pereira Silvia , Barker Robert N , Allen Judith E , Rees Andrew J , Wilson Heather M
Published: June 2011

Macrophages become activated by their environment and develop polarized functions: classically activated (M1) macrophages eliminate pathogens but can cause tissue injury, whereas alternatively activated (M2) macrophages promote healing and repair. Mechanisms directing polarized activation, especially in vivo, are not understood completely, and here, we examined the role of SOCS proteins. M2 macrophages activated in vitro or elicited by implanting mice i.p. with the parasitic nematode Brugia malayi display a selective and IL-4-dependent up-regulation of SOCS1 but not SOCS3. Using siRNA-targeted knockdown in BMDM, we reveal that the enhanced SOCS1 is crucial for IL-4-induced M2 characteristics, including a high arginase I:iNOS activity ratio, suppression of T cell proliferation, attenuated responses to IFN-γ/LPS, and curtailed SOCS3 expression. Importantly, SOCS1 was essential in sustaining the enhanced PI3K activity that drives M2 activation, defining a new regulatory mechanism by which SOCS1 controls M2 polarization. By contrast, for M1 macrophages, SOCS1 was not only an important regulator of proinflammatory mediators (IL-6, IL-12, MHC class II, NO), but critically, for M1, we show that SOCS1 also restricted IL-10 secretion and arginase I activity, which otherwise would limit the efficiency of M1 macrophage proinflammatory responses. Together, our results uncover SOCS1, not only as a feedback inhibitor of inflammation but also as a critical molecular switch that tunes key signaling pathways to effectively program different sides of the macrophage balance.
End-of-life treatment and care: General Medical Council good practice guidance
Authors: Tapley Michael , Jolley David
Published: May 2011

The General Medical Council's guidelines on treatment and care towards the end of life, published in May 2010, contain important guidance for all doctors, including psychiatrists, who care for patients and their families towards the end of life. The document is written in the light of the Mental Capacity Act 2005 and complements existing Good Medical Practice and confidentiality guidelines, also from the General Medical Council. Psychiatrists need to be aware of the communication, legal and ethical issues around end-of-life care, including advance directives and clinically assisted nutrition and hydration. This new guidance is compulsory reading for all psychiatrists.
The adverse consequences of mephedrone use: a case series
Authors: Mackay Kirsty , Taylor Mark , Bajaj Neeraj
Published: May 2011

Aims and method

Mephedrone is a cathinone with amphetamine-like stimulant effects, and is a commonly used recreational drug. The adverse effects of mephedrone use have not been extensively studied. All individuals who self-presented between January and June 2010 to the emergency departments and acute mental health services in Edinburgh and Falkirk with adverse effects of self-reported mephedrone use were identified.

Results

Twenty cases were identified and analysed. Severe agitation was the most common presenting problem (70%), with 40% of individuals developing psychotic symptoms and a further 20% reporting low mood and suicidality. One person died by suicide.

Clinical implications

Mephedrone can produce amphetamine-like adverse psychological intoxication effects, particularly in those with a history of mental illness. Clinicians should consider advising patients on the adverse effects of mephedrone, where relevant.
Vaccination With Patient-Specific Tumor-Derived Antigen in First Remission Improves Disease-Free Survival in Follicular Lymphoma
Authors: Schuster Stephen J. , Neelapu Sattva S. , Gause Barry L. , Janik John E. , Muggia Franco M. , Gockerman Jon P. , Winter Jane N. , Flowers Christopher R. , Nikcevich Daniel A. , Sotomayor Eduardo M. , McGaughey Dean S. , Jaffe Elaine S. , Chong Elise A. , Reynolds Craig W. , Berry Donald A. , Santos Carlos F. , Popa Mihaela A. , McCord Amy M. , Kwak Larry W.
Published: June 2011

Purpose

Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) –specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial.

Patients and Methods

Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control.

Results

Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients.

Conclusion

Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.
Nutritional Governmentality
Authors: Swislocki Mark
Published: June 2011

Among the most powerful metanarratives in discourses on modernity, especially about China, is that of the transition from a condition of premodern food scarcity to one of potential plenty. Employing insights yielded from the recent discoveries of the calorie and of vitamins and minerals, republican Chinese identified patterns of widespread malnutrition throughout the country. Yet a closer look at the documentary record suggests a different historical trajectory than that implied by the scarcity-to-plenty model, with implications for how we think about “empires of food” across the early-modern to modern divide. In China, famine was common but relatively well managed until the modern period, and the late imperial poor, even when living at subsistence levels, appear to have been relatively healthy in nutritional terms. Instead, late imperial Chinese expressed considerable concern about the nutritional health of the rich. They further employed a discourse on nutrition that, unlike modern biomedicine, postulated different nutritional needs and indices of health for people living in different parts of the country. In examining discourses of nutrition in imperial and republican China, this article introduces the idea of “nutritional governmentality,” defined as a state's use of nutritional knowledge to conceptualize its political objectives and administer the health of its population in a manner suitable to meeting those objectives.
Too Hot to Handle
Authors: Padoongpatt Tanachai Mark
Published: June 2011

This article explores the historical roots of the relationship among Thai food, politics, and community formation within the context of global capitalism. It asks why and how Thai food evolved into a powerful community building force for Thai Americans in Los Angeles. Putting the history of Thai Americans in the context of U.S. empire in the Pacific and Southeast Asia, I argue that Thai food is one of the best ways not only to uncover the transnational experiences of Thai Americans but also to understand the way post–World War II U.S. empire has turned foodways into a critical site of racial and ethnic identity formation. Food practices are significant, because they show us that food, as a practice of everyday life, helps people make sense of and imagine their relationship to the world around them. This is an inherently political act.

Drawing from oral histories, Thai- and English-language newspapers, menus, cookbooks, federal and city documents, I discuss the significance of Thai food to Thai Americans in four parts. First, I show how the origins of the Thai culinary scene in Los Angeles spawned not from the arrival of Thai immigrants to U.S. soil but from U.S. intervention in Thailand and the global intensification of tourism during the Cold War. Second, I trace the migration of Thais to Los Angeles and the creation of Thai restaurants as the primary social and community spaces in a period of reindustrialization—or the growth of Los Angeles's service sector economy. Third, I look at how Thai restaurateurs, chefs, and white food critics used Thai food to define the racial, class, and gendered contours of a Thai American identity that was distinct from other Asian groups. Finally, I explain how community leaders tapped into an emerging political discourse of multiculturalism by making Thai food central to Thai American political activism, as well as discuss the limitations of this expression.
“You Say Tomato, I Say Tomahto”
Authors: O'Neill Rebecca
Published: June 2011

Rebecca O'Neill examines the parallel, yet distinct, dialogues that have emerged within food-movement writing and food history. She discusses the growing expectation that food historians contextualize their work in terms of the food movement. The article explores how the tools and methods used by food historians might be applied to the food-movement dialogue. Using John Soluri's Banana Cultures: Agriculture, Consumption, and Environmental Change in Honduras and the United States and Paul Freedman's Out of the East: Spices and the Medieval Imagination as examples, O'Neill argues that the frameworks and concepts used in works of food history can complicate and deepen discussions surrounding the food movement.
“Properly, with love, from scratch”
Authors: Slocum Rachel , Shannon Jerry , Cadieux Kirsten Valentine , Beckman Matthew
Published: June 2011

What to eat is of great concern to the U.S. public; it is the subject of social organizing at many scales and the focus of significant academic discussion. This article analyzes Jamie Oliver's Food Revolution (JOFR), a much-discussed reality show that aired in 2010 in the United States, in which English celebrity chef Jamie Oliver, well known in the United Kingdom for directing government and public attention to school lunch, brought his campaign to promote fresh-cooked food to Huntington, West Virginia. We recognize the capacity of JOFR to encourage people to act on behalf of their and their loved ones' health, as well as to become engaged politically to change the food system, and in this article, we provide a sympathetic critique of themes and methods emphasized by Oliver in his efforts to spark a food revolution. Specifically, our critique points to JOFR's similarity to past food reform efforts; the shaming of the overweight; the focus on a particular form of whiteness that masks the work of race, food, and health; the show's arbitrary designation of authentic food; and JOFR's promotion of heroic, antagonistic change. A food revolution, we argue, needs to engage with structural aspects of the food system through collective action.
Radical Taste
Authors: Trubek Amy B.
Published: June 2011

This article examines, deriving from Aristotelian concepts of the human right to a good life, the moral values that underlie contemporary efforts to transform the food system. Through qualifying labels such as organic, local, artisan, fair trade, healthy, and sustainable, foods are labeled as good or virtuous. Yet the translation of idealized notions of virtuous foods into analysis and action remains problematic, given the tendency of the U.S. moral compass to veer quickly toward the puritanical. The article concludes that a better strategy would be to reject the individual pursuit of virtuous foods and instead work collectively to create other shared values.
Eating in Class
Authors: Bender Daniel , Ankeny Rachel , Belasco Warren , Bentley Amy , Mandala Elias , Pilcher Jeffrey M. , Scholliers Peter
Published: June 2011

In May to July 2010, food historians from across the world gathered virtually to share experiences of teaching food history. The complete, unedited version of our conversation will remain available for public view at www.groups.google.ca/group/rhr-radical-foodways. We encourage Radical History Review readers, students and teachers alike, to continue these discussions online.While food historians can and do make claims that food, like other curricular subjects, matters in and of itself, they must also make connections to broader themes, including histories of empire, commodities, industrialization, and modernity. Food history classes are emerging globally. Perhaps for this very reason, even when food history classes engage with the history of a particular nation or region, the context is frequently transnational and global.
Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish
Authors: Wythe Joshua D. , Jurynec Michael J. , Urness Lisa D. , Jones Christopher A. , Sabeh M. Khaled , Werdich Andreas A. , Sato Mariko , Yost H. Joseph , Grunwald David J. , MacRae Calum A. , Li Dean Y.
Published: June 2011

The vertebrate heart is one of the first organs to form, and its early function and morphogenesis are crucial for continued embryonic development. Here we analyze the effects of loss of Heart adaptor protein 1 (Hadp1), which we show is required for normal function and morphogenesis of the embryonic zebrafish heart. Hadp1 is a pleckstrin homology (PH)-domain-containing protein whose expression is enriched in embryonic cardiomyocytes. Knockdown of hadp1 in zebrafish embryos reduced cardiac contractility and altered late myocyte differentiation. By using optical mapping and submaximal levels of hadp1 knockdown, we observed profound effects on Ca2+ handling and on action potential duration in the absence of morphological defects, suggesting that Hadp1 plays a major role in the regulation of intracellular Ca2+ handling in the heart. Hadp1 interacts with phosphatidylinositol 4-phosphate [PI4P; also known as PtdIns(4)P] derivatives via its PH domain, and its subcellular localization is dependent upon this motif. Pharmacological blockade of the synthesis of PI4P derivatives in vivo phenocopied the loss of hadp1 in zebrafish. Collectively, these results demonstrate that hadp1 is required for normal cardiac function and morphogenesis during embryogenesis, and suggest that hadp1 modulates Ca2+ handling in the heart through its interaction with phosphatidylinositols.
Unbound (bioavailable) IGF1 enhances somatic growth
Authors: Elis Sebastien , Wu Yingjie , Courtland Hayden-William , Cannata Dara , Sun Hui , Beth-On Mordechay , Liu Chengyu , Jasper Hector , Domené Horacio , Karabatas Liliana , Guida Clara , Basta-Pljakic Jelena , Cardoso Luis , Rosen Clifford J. , Frystyk Jan , Yakar Shoshana
Published: June 2011

Understanding insulin-like growth factor-1 (IGF1) biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging. IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs) and the acid labile subunit (ALS), which are present in serum and tissues. To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice) or R3-Igf1 (KIR mice). The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or ‘free IGF1’. We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels. Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type. Both mutant mice showed increased body weight, body and bone lengths, and relative lean mass. We found selective organomegaly of the spleen, kidneys and uterus, enhanced mammary gland complexity, and increased skeletal acquisition. The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions.
Increased ER–mitochondrial coupling promotes mitochondrial respiration and bioenergetics during early phases of ER stress
Authors: Bravo Roberto , Vicencio Jose Miguel , Parra Valentina , Troncoso Rodrigo , Munoz Juan Pablo , Bui Michael , Quiroga Clara , Rodriguez Andrea E. , Verdejo Hugo E. , Ferreira Jorge , Iglewski Myriam , Chiong Mario , Simmen Thomas , Zorzano Antonio , Hill Joseph A. , Rothermel Beverly A. , Szabadkai Gyorgy , Lavandero Sergio
Published: June 2011

Increasing evidence indicates that endoplasmic reticulum (ER) stress activates the adaptive unfolded protein response (UPR), but that beyond a certain degree of ER damage, this response triggers apoptotic pathways. The general mechanisms of the UPR and its apoptotic pathways are well characterized. However, the metabolic events that occur during the adaptive phase of ER stress, before the cell death response, remain unknown. Here, we show that, during the onset of ER stress, the reticular and mitochondrial networks are redistributed towards the perinuclear area and their points of connection are increased in a microtubule-dependent fashion. A localized increase in mitochondrial transmembrane potential is observed only in redistributed mitochondria, whereas mitochondria that remain in other subcellular zones display no significant changes. Spatial re-organization of these organelles correlates with an increase in ATP levels, oxygen consumption, reductive power and increased mitochondrial Ca2+ uptake. Accordingly, uncoupling of the organelles or blocking Ca2+ transfer impaired the metabolic response, rendering cells more vulnerable to ER stress. Overall, these data indicate that ER stress induces an early increase in mitochondrial metabolism that depends crucially upon organelle coupling and Ca2+ transfer, which, by enhancing cellular bioenergetics, establishes the metabolic basis for the adaptation to this response.
Completion Rates and Time-to-Degree in Economics PhD Programs
Authors: Stock Wendy A , Siegfried John J , Finegan T. Aldrich
Published: June 2011

This paper describes the progress, eight years after matriculating, of 586 individuals who entered one of 27 economics Ph.D. programs in fall 2002. By October 2010, 59 percent of the fall 2002 entering cohort had earned a Ph.D. in economics at the university where they initially matriculated, 37 percent had dropped out, and 4 percent were still writing their dissertations.We examine student outcomes by Ph.D. program tier and investigate factors associated with completion and time to degree. We document and describe the rise in median time to degree from 5.0 to 5.6 years during the period 1996–2010.
A Bright Idea for Measuring Economic Growth
Authors: Henderson Vernon , Storeygard Adam , Weil David N
Published: June 2011

The quantity of human-generated light visible from outer space reflects variation in both population density and income per capita. In this paper we explore the usefulness of the change in visible light as a measure of GDP growth. We discuss the data, and then present a statistical framework that uses lights growth to augment existing income growth measures, assuming that measurement errors in the two series are uncorrelated. For some countries with very poor income measurement, we significantly revise estimates of growth. Our technique also produces growth estimates for cities or regions where no other data are available.
Quality Adjustment for Health Care Spending on Chronic Disease: Evidence from Diabetes Treatment, 1999–2009
Authors: Eggleston Karen N , Shah Nilay D , Smith Steven A , Berndt Ernst R , Newhouse Joseph P
Published: June 2011

Although US health care expenditures reached 17.6 percent of GDP in 2009, quality measurement in this important service sector remains limited. Studying quality changes associated with 11 years of health care for patients with diabetes, we find that the value of reduced mortality and avoided treatment spending, net of the increase in annual spending, was $9,094 for the average patient. These results suggest that the unit cost of diabetes treatment, adjusting for the value of health outcomes, has been roughly constant. Since input prices have not been declining, our results are consistent with productivity improvement in health care.
Recessions, Retirement, and Social Security
Authors: Coile Courtney C , Levine Phillip B
Published: June 2011

This paper examines how labor market fluctuations around the time of retirement affect the labor force status and Social Security receipt of individuals ages 55 to 69 and the income of retirees in their 70s, using data from the March Current Population Survey, Census, and American Community Surveys. We find that workers are more likely to leave the labor force, to collect Social Security earlier, and to have lower Social Security income when they face a recession near retirement. The impact is greatest for the less-educated, who are more susceptible to job loss and rely more heavily on Social Security.
Why Can't US Airlines Make Money?
Authors: Borenstein Severin
Published: June 2011

US airlines have lost nearly $60 billion ($2009) in domestic markets since the 1978 deregulation, most of it in the last decade. The dismal financial record challenges the economics of deregulation. I examine some of the common explanations among industry participants and researchers—including high taxes and fuel costs, weak demand, and competition from lower-cost airlines. Major drivers seem to be the demand downturn after 9/11—demand remains much weaker today than in 2000—and the large cost differential between legacy and low-cost carriers, which has persisted even as the price differential between them has greatly declined.
Measuring the Benefits of Greater Spatial Granularity in Short-Term Pricing in Wholesale Electricity Markets
Authors: Wolak Frank A
Published: June 2011

Hourly generation unit-level output levels, detailed information on the technological characteristics of generation units, and daily delivered natural gas prices to all generation units for the California wholesale electricity market before and after the implementation of locational marginal pricing are used to measure the impact of introducing greater spatial granularity in short-term energy pricing. The average hourly number of generation unit starts increases, but both the total hourly energy consumed and total hourly operating costs for all natural gas-fired generation units fall by more than 2 percent after the implementation of locational marginal pricing.
Predicting and Preventing Shootings among At-Risk Youth
Authors: Chandler Dana , Levitt Steven D , List John A
Published: June 2011

Each year, more than 250 students in the Chicago Public Schools (CPS) are shot. The authors of this paper worked with the leadership of CPS to build a predictive model of shootings that helped determine which students would be included in a highly targeted and resource intensive mentorship program. This paper describes our predictive model and offers a preliminary evaluation of the mentoring intervention performed by Youth Advocate Programs, Inc. (YAP). We find little evidence that the intervention reduces school misconducts or improves educational outcomes. The scale of intervention was too small to generate meaningful findings on shootings.
US Trade and Inventory Dynamics
Authors: Alessandria George , Kaboski Joseph P , Midrigan Virgiliu
Published: June 2011

We examine the source of the large fall and rebound in US trade in the recent recession. While trade fell and rebounded more than expenditures or production of traded goods, we find that relative to the magnitude of the downturn, these trade fluctuations were in line with those in previous business cycle fluctuations. We argue that the high volatility of trade is attributed to more severe inventory management considerations of firms involved in international trade. We present empirical evidence for autos as well as at the aggregate level that the adjustment of inventory holdings help explain these fluctuations in trade.