bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity and mortality among older Thais: a four year follow up study
Authors: Vapattanawong Patama , Aekplakorn Wichai , Rakchanyaban Uthaithip , Prasartkul Pramote , Porapakkham Yawarat
Published: October 2010

Background

To assess the association of body mass index with mortality in a population-based setting of older people in Thailand.

Methods

Baseline data from the National Health Examination Survey III (NHES III) conducted in 2004 was linked to death records from vital registration for 2004-2007. Complete information regarding body mass index (BMI) (n = 15997) and mortality data were separately analysed by sex. The Cox Proportional Hazard Model was used to test the association between BMI and all-cause mortality controlling for demographic, socioeconomic, and health risk factors.

Results

During a mean follow-up time of 3.8 years (60545.8 person-years), a total of 1575 older persons, (936 men and 639 women) had died. A U-shaped and reverse J-shaped of association between BMI and all-cause mortality were observed in men and women, respectively. However there was no significant increased risk in the higher BMI categories. Compared to those with BMI 18.5-22.9 kg/m2, the adjusted hazard ratios (HR) of all-cause mortality for those with BMI <18.5, 23.0-24.9, 25.0-27.4, 27.5-29.9, 30.0-34.9, and ≥35.0 were 1.34 (95% CI, 1.14-1.58), 0.79 (95% CI, 0.65-0.97), 0.81 (95% CI, 0.65-1.00), 0.67 (95% CI, 0.48-0.94), 0.60 (95% CI, 0.35-1.03), and 1.87 (95% CI, 0.77-4.56), respectively, for men, and were 1.29 (95% CI,1.04-1.60), 0.70 (95% CI, 0.55-0.90), 0.79 (95% CI, 0.62-1.01), 0.57 (95% CI, 0.41-0.81), 0.58 (95% CI, 0.39-0.87), and 0.78 (95% CI, 0.38-1.59), respectively, for women.

Conclusions

The results of this study support the obesity paradox phenomenon in older Thai people, especially in women. Improvement in quality of mortality data and further investigation to confirm such association are needed in this population.
Pharmacokinetics of artemether and dihydroartemisinin in healthy Pakistani male volunteers treated with artemether-lumefantrine
Authors: Ali Shabana , Najmi Muzammil H , Tarning Joel , Lindegardh Niklas
Published: October 2010

Background

Artemether-lumefantrine is one of the most widely used anti-malarial drug combinations in the world with excellent tolerability and cure rates in adult and paediatric patients with uncomplicated falciparum malaria. The aim of this study was to evaluate the pharmacokinetics of artemether and its active metabolite, dihydroartemisinin, in healthy Pakistani volunteers.

Methods

Twelve healthy male Pakistani subjects, aged 20 to 50, were recruited into the study. A fixed oral combination of artemether-lumefantrine (80-480 mg) was given as a single oral dose. Frequent blood samples were collected and artemether and dihydroartemisinin were quantified in human plasma using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. Drug concentration-time data were evaluated with non-compartmental analysis.

Results

Observed maximum concentrations (mean ± SD) of artemether and dihydroartemisinin were 184 ± 100 ng/mL and 126 ± 46 ng/mL, respectively. These concentrations were reached at 1.56 ± 0.68 hr and 1.69 ± 0.59 hr, respectively, after drug intake. The terminal elimination half-life of artemether and dihydroartemisinin were 2.00 ± 0.71 hr and 1.80 ± 0.31 hr, respectively. Apparent volume of distribution and oral clearance for artemether were estimated to 666 ± 220 L and 257 ± 140 L/hr. The same parameters were estimated to 702 ± 220 L and 269 ± 57 L/hr for dihydroartemisinin.

Conclusions

The overall pharmacokinetic properties of artemether and dihydroartemisinin in healthy Pakistani subjects are comparable to healthy subjects and patients from other populations.
Specific antibody responses against membrane proteins of erythrocytes infected by Plasmodium falciparum of individuals briefly exposed to malaria
Authors: Fontaine Albin , Pophillat Matthieu , Bourdon Stéphanie , Villard Claude , Belghazi Maya , Fourquet Patrick , Durand Claude , Lefranc Didier , Rogier Christophe , Fusai Thierry , Almeras Lionel
Published: October 2010

Background

Plasmodium falciparuminfections could lead to severe malaria, principally in non-immune individuals as children and travellers from countries exempted of malaria. Severe malaria is often associated with the sequestration ofP. falciparum-infected erythrocytes in deep micro-vascular beds via interactions between host endothelial receptors and parasite ligands expressed on the surface of the infected erythrocyte. Although, serological responses from individuals living in endemic areas against proteins expressed at surface of the infected erythrocyte have been largely studied, seldom data are available about the specific targets of antibody response from travellers.

Methods

In order to characterize antigens recognized by traveller sera, a comparison of IgG immune response against membrane protein extracts from uninfected andP. falciparum-infected red blood cells (iRBC), using immunoblots, was performed between non exposed individuals (n=31) and briefly exposed individuals (BEI)(n = 38) to malaria transmission.

Results

Immune profile analysis indicated that eight protein bands from iRBC were significantly detected more frequently in the BEI group. Some of these antigenic proteins were identified by an original immuno-proteomic approach.

Conclusion

Collectively, these data may be useful to characterize the singular serological immune response against a primary malaria infection in individuals briefly exposed to transmission.
Identification and characterization of the Plasmodium vivax thrombospondin-related apical merozoite protein
Authors: Mongui Alvaro , Angel Diana I , Moreno-Perez Darwin A , Villarreal-Gonzalez Silvana , Almonacid Hannia , Vanegas Magnolia , Patarroyo Manuel A
Published: October 2010

Background

Malaria caused by Plasmodium vivax is a major public health problem worldwide that affects 70-80 million people in the Middle East, Asia, Western Pacific, South America and the Caribbean. Despite its epidemiological importance, few antigens from this parasite species have been characterized to date compared to Plasmodium falciparum, due in part to the difficulties of maintaining an in vitro culture of P. vivax. This study describes the identification of the P. falciparum thrombospondin-related apical merozoite protein homologue in P. vivax (PvTRAMP) and examines its potential to be further evaluated as vaccine candidate.

Methods

The gene encoding PvTRAMP was identified through an extensive search of the databases hosting the genome sequence of P. vivax. Genes adjacent to pvtramp were identified in silico to determine the degree of similarity between the protein sequences encoded by equivalent chromosomic fragments in P. falciparum and Plasmodium knowlesi. The pvtramp gene was amplified from cDNA of P. vivax schizont stages, cloned and expressed in Escherichia coli. Anti-PvTRAMP antisera was obtained by inoculating rabbits with PvTRAMP B cell epitopes produced as synthetic peptides in order to assess its recognition in parasite lysates by Western blot and in intact parasites by indirect immunofluorescence. The recognition of recombinant PvTRAMP by sera from P. vivax- infected individuals living in endemic areas was also assessed by ELISA.

Results

The PfTRAMP homologue in P. vivax, here denoted as PvTRAMP, is a 340-amino-acid long antigen encoded by a single exon that could have a potential role in cytoadherence, as indicated by the presence of a thrombospondin structural homology repeat (TSR) domain. According to its transcription and expression profile, PvTRAMP is initially located at the parasite's apical end and later on the parasite surface. Recombinant PvTRAMP is recognized by sera from infected patients, therefore, indicating that it is targeted by the immune system during a natural infection with P. vivax.

Conclusions

The results of this work support conducting further studies with PvTRAMP to evaluate its immunogenicity and protection-inducing ability in the Aotus animal model.
The characteristics of dyslipidemia patients with different durations in Beijing: a cross-sectional study
Authors: Liu Yingying , Zhang Puhong , Wang Wei , Wang Huan , Zhang Ling , Wu Wei , Guo Xiuhua
Published: October 2010

Background

Prevalence of dyslipidemia is high and increases even in younger people. The key aim of this study was to explore the group characteristics of patients in different durations of dyslipidemia and provide clues for the management of dyslipidemia in Beijing.

Results

Patients with short duration of dyslipidemia were mainly characterized by relatively young age, occupational groups, not eating or irregular eating breakfast, less physical activities, having the habit of smoking, and 53.8% is with abnormal LDL-c, 10.4% is with abnormal HDL-c, and 51.5% is with abnormal TG. 54.6% of patients with longer duration is with abnormal LDL-c, 12.8% of them is with abnormal HDL-c, and 57.1% is with abnormal TG. They paid much more attentions to their health, tried to eat breakfast regularly and do more physical activities, gave up smoking, and had regular breakfast, but increasing physiological disorders such as elevated blood pressure and glucose appeared. Severe sequelaes (stroke, myocardial infarction) were mainly observed in patients with the duration of more than 10 years. And in this group the proportions of patients with LDL-c ≥ 4.15 mmol/L and TG ≥ 4.53 mmol/L are the highest among the three groups.

Conclusions

we should strengthen the tertiary prevention and improve the control rate of dyslipidemia in Beijing. Health promotion programs such as tobacco control and physical exercise should be carried out for younger patients.
Shortcomings of short hairpin RNA-based transgenic RNA interference in mouse oocytes
Authors: Sarnova Lenka , Malik Radek , Sedlacek Radislav , Svoboda Petr
Published: October 2010

Background

RNA interference (RNAi) is a powerful approach to study a gene function. Transgenic RNAi is an adaptation of this approach where suppression of a specific gene is achieved by expression of an RNA hairpin from a transgene. In somatic cells, where a long double-stranded RNA (dsRNA) longer than 30 base-pairs can induce a sequence-independent interferon response, short hairpin RNA (shRNA) expression is used to induce RNAi. In contrast, transgenic RNAi in the oocyte routinely employs a long RNA hairpin. Transgenic RNAi based on long hairpin RNA, although robust and successful, is restricted to a few cell types, where long double-stranded RNA does not induce sequence-independent responses. Transgenic RNAi in mouse oocytes based on a shRNA offers several potential advantages, including simple cloning of the transgenic vector and an ability to use the same targeting construct in any cell type.

Results

Here we report our experience with shRNA-based transgenic RNAi in mouse oocytes. Despite optimal starting conditions for this experiment, we experienced several setbacks, which outweigh potential benefits of the shRNA system. First, obtaining an efficient shRNA is potentially a time-consuming and expensive task. Second, we observed that our transgene, which was based on a common commercial vector, was readily silenced in transgenic animals.

Conclusions

We conclude that, the long RNA hairpin-based RNAi is more reliable and cost-effective and we recommend it as a method-of-choice when a gene is studied selectively in the oocyte.
Plan comparison of volumetric-modulated arc therapy (RapidArc) and conventional intensity-modulated radiation therapy (IMRT) in anal canal cancer
Authors: Vieillot Sabine , Azria David , Lemanski Claire , Moscardo Carmen Llacer , Gourgou Sophie , Dubois Jean-Bernard , Aillères Norbert , Fenoglietto Pascal
Published: October 2010

Background

To compare volumetric-modulated arc therapy (RapidArc) plans with conventional intensity-modulated radiation therapy (IMRT) plans in anal canal cancers.

Methods

Ten patients with anal canal carcinoma previously treated with IMRT in our institution were selected for this study. For each patient, three plans were generated with the planning CT scan: one using a fixed beam IMRT, and two plans using the RapidArc technique: a single (RA1) and a double (RA2) modulated arc therapy. The treatment plan was designed to deliver in one process with simultaneous integrated boost (SIB) a dose of 59.4 Gy to the planning target volume (PTV2) based on the gross disease in a 1.8 Gy-daily fraction, 5 days a week. At the same time, the subclinical disease (PTV1) was planned to receive 49.5 Gy in a 1.5 Gy-daily fraction. Plans were normalized to 99% of the PTV2 that received 95% of the prescribed dose. Planning objectives were 95% of the PTV1 will receive 95% of the prescribed dose and no more than 2% of the PTV will receive more than 107%. Dose-volume histograms (DVH) for the target volume and the organs at risk (bowel tract, bladder, iliac crests, femoral heads, genitalia/perineum, and healthy tissue) were compared for these different techniques. Monitor units (MU) and delivery treatment time were also reported.

Results

All plans achieved fulfilled objectives. Both IMRT and RA2 resulted in superior coverage of PTV than RA1 that was slightly inferior for conformity and homogeneity (p < 0.05).

Conformity index (CI95%) for the PTV2 was 1.15 ± 0.15 (RA2), 1.28 ± 0.22 (IMRT), and 1.79 ± 0.5 (RA1). Homogeneity (D5% - D95%) for PTV2 was 3.21 ± 1.16 Gy (RA2), 2.98 ± 0.7 Gy (IMRT), and 4.3 ± 1.3 Gy (RA1). RapidArc showed to be superior to IMRT in terms of organ at risk sparing. For bowel tract, the mean dose was reduced of 4 Gy by RA2 compared to IMRT. Similar trends were observed for bladder, femoral heads, and genitalia. The DVH of iliac crests and healthy tissue resulted in comparable sparing for the low doses (V10 and V20). Compared to IMRT, mean MUs for each fraction was significantly reduced with RapidArc (p = 0.0002) and the treatment time was reduced by a 6-fold extent.

Conclusion

For patients suffering from anal canal cancer, RapidArc with 2 arcs was able to deliver equivalent treatment plan to IMRT in terms of PTV coverage. It provided a better organ at risk sparing and significant reductions of MU and treatment time per fraction.
Stunting and soil-transmitted-helminth infections among school-age pupils in rural areas of southern China
Authors: Shang Yu , Tang Lin-Hua , Zhou Shui-Sen , Chen Ying-Dan , Yang Yi-Chao , Lin Shao-Xiong
Published: October 2010

Background

Stunting and soil-transmitted helminth (STH) infections including ascariasis, trichuriasis and hookworm remain major public health problems in school-age pupils in developing countries. The objectives of this study were to determine the prevalence of stunting for children and its association with three major soil-transmitted helminths (STH) in rural areas of southern China. The study also aims to determine risk factors for stunting and to provide guidance on the prevention and control of stunting and STH infections for future studies in this field.

Results

A cross-sectional survey was carried out in the poor rural areas in Guangxi Autonomous Regional and Hainan Province where STH prevalence was higher between September and November 2009. Pupils were from 15 primary schools. All the school-age pupils aged between 9 and 12 years old (mean age 11.2 ± 3.2 years), from grades three to six took part in this study. Study contents include questionnaire surveys, physical examination and laboratory methods (stool checking for eggs of three major STH infections and haemoglobin determination was performed for the anaemia test). Finally 1031 school-age pupils took part in survey. The results showed that the overall prevalence of stunting (HAZ < 2SD) was 25.6%, based on the WHO Child Growth Standards (2007). Risk factors for stunting based on logistic regression analyses were: (1) STH moderate-to-heavy intensity infections (OR = 1.93;95%CI:1.19,3.11); (2) anaemia (OR = 3.26;95%CI: 2.02,5.27); (3) education level of mother (OR = 2.13; 95%CI: 1.39,3.25). The overall prevalence of major STH infections was 36.7%, STH moderate-to-heavy intensity infections was 16.7%. The overall prevalence of ascariasis, trichuriasis, hookworm and co-infection were 18.5%, 11.2%, 14.7% and 9.1% respectively. The prevalence of anaemic children (HB < 12 g/dl) was 13.1%.

Conclusion

The present study showed that stunting was highly prevalent among the study population and STH infection is one of the important risk factors for stunting, with moderate-to-heavy intensity infections being the main predictor of stunting. Hence, additional interventions measures such as to promote de-worming treatment, to enhance health education and to improve hygiene and sanitation in order to reduce stunting in this population, are needed throughout the primary school age group.
Changes in androgens and insulin sensitivity indexes throughout pregnancy in women with polycystic ovary syndrome (PCOS): relationships with adverse outcomes
Authors: Falbo Angela , Rocca Morena , Russo Tiziana , D'Ettore Antonietta , Tolino Achille , Zullo Fulvio , Orio Francesco , Palomba Stefano
Published: October 2010

Background

Given the high rate of pregnancy and perinatal complications recently observed in patients with polycystic ovary syndrome (PCOS) and the lack of data on the serum variations in androgens and insulin sensitivity indexes in pregnant women with PCOS, the current study was aimed to assess these changes and their potential effect on pregnancy outcomes in a population of women with PCOS.

Methods

Forty-five pregnant patients with ovulatory PCOS (PCOS group) and other 42 healthy pregnant women (control group) were studied assaying serum androgen levels and insulin sensitivity indexes throughout pregnancy serially, and recording obstetrical outcomes.

Results

Serum androgen levels and insulin resistance indexes were significantly (p < 0.05) higher in PCOS than in control group at study entry, these differences were sustained throughout pregnancy, and their changes resulted significantly (p < 0.05) different between PCOS and control group. In PCOS patients, women who had a complicated pregnancy showed serum androgen levels and insulin sensitivity indexes significantly (p < 0.05) worse in comparison to subjects without any pregnancy and/or neonatal complications.

Conclusions

PCOS patients have impaired changes in serum androgen levels and insulin sensitivity indexes during pregnancy. These alterations could be implicated in the pregnancy and neonatal complications frequently observed in women affected by PCOS.
Simple tricks for improving pattern-based information extraction from the biomedical literature
Authors: Nguyen Quang Long , Tikk Domonkos , Leser Ulf
Published: October 2010

Background

Pattern-based approaches to relation extraction have shown very good results in many areas of biomedical text mining. However, defining the right set of patterns is difficult; approaches are either manual, incurring high cost, or automatic, often resulting in large sets of noisy patterns.

Results

We propose several techniques for filtering sets of automatically generated patterns and analyze their effectiveness for different extraction tasks, as defined in the recent BioNLP 2009 shared task. We focus on simple methods that only take into account the complexity of the pattern and the complexity of the texts the patterns are applied to. We show that our techniques, despite their simplicity, yield large improvements in all tasks we analyzed. For instance, they raise the F-score for the task of extraction gene expression events from 24.8% to 51.9%.

Conclusions

Already very simple filtering techniques may improve the F-score of an information extraction method based on automatically generated patterns significantly. Furthermore, the application of such methods yields a considerable speed-up, as fewer matches need to be analysed. Due to their simplicity, the proposed filtering techniques also should be applicable to other methods using linguistic patterns for information extraction.
Influence of depression symptoms on serum tumor necrosis factor-α of patients with chronic low back pain
Authors: Wang Haili , Ahrens Carsten , Rief Winfried , Gantz Simone , Schiltenwolf Marcus , Richter Wiltrud
Published: October 2010

Introduction

Patients with chronic low back pain (cLBP) have high rates of comorbid psychiatric disorders, mainly depression. Recent evidence suggests that depressive symptoms and pain, as interacting factors, have an effect on the circulating levels of inflammatory markers relevant to coronary artery disease. Our previous work showed a higher serum level of an inflammatory marker tumour necrosis factor-alpha (TNFα) in patients with cLBP, which did not correlate with intensity of low back pain alone. In the present study we investigated the cross-sectional associations of depressive symptoms, low back pain and their interaction with circulating levels of TNFα.

Methods

Each group of 29 patients with cLBP alone or with both cLBP and depression was age-matched and sex-matched with 29 healthy controls. All subjects underwent a blood draw for the assessment of serum TNFα and completed a standardised questionnaire regarding medication, depression scores according to the German version of Centre for Epidemiological Studies Depression Scale (CES-D), pain intensity from a visual analogue scale, and back function using the Roland and Morris questionnaire. The correlations between TNFα level and these clinical parameters were analysed.

Results

There were no differences in TNFα level between cLBP patients with and without depression. Both cLBP patients with (median = 2.51 pg/ml, P = 0.002) and without (median = 2.58 pg/ml, P = 0.004) depression showed significantly higher TNFα serum levels than healthy controls (median = 0 pg/ml). The pain intensity reported by both patient groups was similar, while the patients with depression had higher CES-D scores (P < 0.001) and worse back function (P < 0.001). The variance analysis showed that the interaction between TNFα level and pain intensity, CES-D scores, sex, body mass index and medication was statistically significant.

Conclusions

Depression as a comorbidity to cLBP did not influence the serum TNFα level. It seems that TNFα somehow acts as a mediator in both cLBP and depression, involving similar mechanisms that will be interesting to follow in further studies.
Pivotal Advance: The promotion of soluble DC-SIGN release by inflammatory signals and its enhancement of cytomegalovirus-mediatedcis-infection of myeloid dendritic cells
Authors: Plazolles N , Humbert J-M , Vachot L , Verrier B , Hocke C , Halary F
Published: October 2010

DC-SIGN is a member of the C-type lectin family. Mainly expressed by myeloid DCs, it is involved in the capture and internalization of pathogens, including human CMV. Several transcripts have been identified, some of which code for putative soluble proteins. However, little is known about the regulation and the functional properties of such putative sDC-SIGN variants. To better understand how sDC-SIGN could be involved in CMV infection, we set out to characterize biochemical and functional properties of rDC-SIGN as well as naturally occurring sDC-SIGN. We first developed a specific, quantitative ELISA and then used it to detect the presence sDC-SIGN in in vitro-generated DC culture supernatants as cell-free secreted tetramers. Next, in correlation with their inflammatory status, we demonstrated the presence of sDC-SIGN in several human body fluids, including serum, joint fluids, and BALs. CMV infection of human tissues was also shown to promote sDC-SIGN release. Based on the analysis of the cytokine/chemokine content of sDC-SIGN culture supernatants, we identified IFN-γ and CXCL8/IL-8 as inducers of sDC-SIGN production by MoDC. Finally, we demonstrated that sDC-SIGN was able to interact with CMV gB under native conditions, leading to a significant increase in MoDC CMV infection. Overall, our results confirm that sDC-SIGN, like its well-known, counterpart mDC-SIGN, may play a pivotal role in CMV-mediated pathogenesis.
CCL22 regulates experimental autoimmune encephalomyelitis by controlling inflammatory macrophage accumulation and effector function
Authors: Dogan Rukiye-Nazan E , Long Nancy , Forde Eileen , Dennis Kristen , Kohm Adam P , Miller Stephen D , Karpus William J
Published: October 2010

EAE is a demyelinating disease of the CNS and serves as a mouse model of MS. Expression of CCL22 in the draining LNs and spinal cord correlated with the onset of clinical EAE development and remained elevated. Administration of anti-CCL22 at the time of autoantigen immunization delayed the initiation of clinical disease and dampened the severity of peak initial disease and relapses. Reduced EAE severity correlated with the reduction of pathology and leukocytes in the CNS, particularly, activated CD11b+Ly6Chi macrophages. There were no differences in effector T cell-proliferative responses or effector T cell IFN-γ or IL-17 responses. However, treatment at the onset of disease did not reduce disease progression. Treatment of adoptive T cell transfer recipient mice with anti-CCL22 resulted in decreased clinical disease development accompanied by a decrease in CNS accumulation of CD11b+Ly6Chi macrophages. Neutralization of CCL22 resulted in a macrophage population whose effector cytokine expression consisted of decreased TNF and increased IL-10, a phenotype more consistent with M2 macrophages. This was corroborated by in vitro cultures of macrophages with CCL22. These results suggest that CCL22 functions to regulate development of EAE through macrophage chemoattraction and effector function.
Atrial Fibrillation and Stroke Associated With Intravenous Bisphosphonate Therapy in Older Patients With Cancer
Authors: Wilkinson Gregg S. , Baillargeon Jacques , Kuo Yong-Fang , Freeman Jean L. , Goodwin James S.
Published: October 2010

Purpose

Recent studies have linked the use of intravenous and orally administered bisphosphonates with subsequent development of atrial fibrillation. Patients with cancer who receive intravenous bisphosphonate therapy may be at particular risk for this adverse event because they receive higher doses of these drugs than do patients treated for other indications. We examined the association of intravenous bisphosphonates with atrial fibrillation, all classifications of supraventricular tachycardia (SVT), and stroke among older patients with cancer.

Patients and Methods

Using Surveillance, Epidemiology, and End Results (SEER) -Medicare–linked data, we identified older (≥ age 65 years) patients with cancer who were treated with intravenous infusions of bisphosphonates between January 1, 1995 and December 31, 2003. We then matched 13,714 bisphosphonate nonusers to 6,857 bisphosphonate users, at a 2:1 ratio, on cancer type, age, sex, presence of bone metastases, and SEER geographic region. Patients were observed until December 31, 2003 or until they lost coverage from Medicare Parts A and B; enrolled in a health maintenance organization; received a diagnosis of atrial fibrillation, any SVT, or stroke; or died.

Results

Receipt of intravenous bisphosphonates was modestly associated with an increased risk for atrial fibrillation (hazard ratio [HR] = 1.30; 95% CI, 1.18 to 1.43), all SVT (HR = 1.28; 95% CI, 1.19 to 1.38), and stroke (HR = 1.30; 95% CI, 1.09 to 1.54). The risk for all SVT increased 7% for each increase of five bisphosphonate dose equivalents (HR = 1.07; 95% CI, 1.02 to 1.12).

Conclusion

Clinicians who treat patients with cancer who have received intravenous bisphosphonates should be aware of the possible cardiovascular adverse events associated with this treatment.
Second Malignancy Risks After Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia: Differences by Lymphoma Subtype
Authors: Morton Lindsay M. , Curtis Rochelle E. , Linet Martha S. , Bluhm Elizabeth C. , Tucker Margaret A. , Caporaso Neil , Ries Lynn A.G. , Fraumeni Joseph F.
Published: October 2010

Purpose

Previous studies have shown increased risks of second malignancies after non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL); however, no earlier investigation has quantified differences in risk of new malignancy by lymphoma subtype.

Patients and Methods

We evaluated second cancer and leukemia risks among 43,145 1-year survivors of CLL/small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL) from 11 Surveillance, Epidemiology, and End Results (SEER) population-based registries during 1992 to 2006.

Results

Among patients without HIV/AIDS–related lymphoma, lung cancer risks were significantly elevated after CLL/SLL and FL but not after DLBCL (standardized incidence ratio [SIR], CLL/SLL = 1.42, FL = 1.28, DLBCL = 1.00; Poisson regression P for difference among subtypes, PDiff = .001). A similar pattern was observed for risk of cutaneous melanoma (SIR: CLL/SLL = 1.92, FL = 1.60, DLBCL = 1.06; PDiff = .004). Acute nonlymphocytic leukemia risks were significantly elevated after FL and DLBCL, particularly among patients receiving initial chemotherapy, but not after CLL/SLL (SIR: CLL/SLL = 1.13, FL = 5.96, DLBCL = 4.96; PDiff < .001). Patients with HIV/AIDS–related lymphoma (n = 932) were predominantly diagnosed with DLBCL and had significantly and substantially elevated risks for second anal cancer (SIR = 120.50) and Kaposi's sarcoma (SIR = 138.90).

Conclusion

Our findings suggest that differing immunologic alterations, treatments (eg, alkylating agent chemotherapy), genetic susceptibilities, and other risk factors (eg, viral infections, tobacco use) among lymphoma subtypes contribute to the patterns of second malignancy risk. Elucidating these patterns may provide etiologic clues to lymphoma as well as to the second malignancies.
Survival Patterns in Patients With Hodgkin's Lymphoma With a Pre-Existing Hospital Discharge Diagnosis of Autoimmune Disease
Authors: Landgren Ola , Pfeiffer Ruth M. , Kristinsson Sigurdur Y. , Björkholm Magnus
Published: October 2010

Purpose

Autoimmune diseases (AIs) are associated with elevated risk for Hodgkin's lymphoma (HL); however, information on the interplay of AIs and HL on survival is sparse.

Patients and Methods

We evaluated survival patterns for 7,414 patients with HL in relation to a pre-existing hospital discharge diagnosis of an AI. We also assessed survival patterns in relation to a prior AI diagnosis among 29,240 population-based matched controls.

Results

Among female patients with HL with (v those without) a pre-existing AI, the 5-year and 10-year overall survival was 46.0% (63.3%) and 41.0% (51.9%); for males, the corresponding numbers were 48.5% (59.2%) and 43.6% (51.5%), respectively (P < .001). Among female controls with (v those without) a pre-existing AI, the 5-year and 10-year overall survival was 79.1% (90.2%) and 67.2% (83.3%); for males, the corresponding numbers were 82.5% (90.3%) and 68.6% (81.6%), respectively (P < .001). Female patients with HL with (v those without) a pre-existing AI had a 1.8-fold (range, 1.3- to 2.4-fold) increased relative risk of dying at 5 years of follow-up; for males, the corresponding excess relative risk of dying was 1.7-fold (range, 1.3- to 2.2-fold).

Conclusion

Patients with HL have an overall excellent outcome from treatment but also pose some of the most complex challenges of cancer survivorship due to many late effects (eg, second malignancies, thyroid disease, cardiovascular disease, and altered reproductive and sexual function). Our finding that patients with HL with a hospital discharge diagnosis of an AI have a substantially higher risk of dying, emphasizes that underlying chronic diseases, such as AIs, should be high of the list of survivorship concerns for clinicians that treat HL.
Survival and Prognostic Factors of Early Childhood Medulloblastoma: An International Meta-Analysis
Authors: Rutkowski Stefan , von Hoff Katja , Emser Angela , Zwiener Isabella , Pietsch Torsten , Figarella-Branger Dominique , Giangaspero Felice , Ellison David W. , Garre Maria-Luisa , Biassoni Veronica , Grundy Richard G. , Finlay Jonathan L. , Dhall Girish , Raquin Marie-Anne , Grill Jacques
Published: October 2010

Purpose

To assess the prognostic role of clinical parameters and histology in early childhood medulloblastoma.

Patients and Methods

Clinical and histologic data from 270 children younger than age 5 years diagnosed with medulloblastoma between March 1987 and July 2004 and treated within prospective trials of five national study groups were centrally analyzed.

Results

Two hundred sixty children with medulloblastoma and specified histologic subtype were eligible for analysis (median age, 1.89 years; median follow-up, 8.0 years). Rates for 8-year event-free survival (EFS) and overall survival (OS) were 55% and 76%, respectively, in 108 children with desmoplastic/nodular medulloblastoma (DNMB) or medulloblastoma with extensive nodularity (MBEN); 27% and 42%, respectively, in 145 children with classic medulloblastoma (CMB); and 14% and 14%, respectively, in seven children with large-cell/anaplastic (LC/A) medulloblastoma (P < .001). Histology (DNMB/MBEN: hazard ratio [HR], 0.44; 95% CI, 0.31 to 0.64; LC/A medulloblastoma: HR, 2.27; 95% CI, 0.95 to 5.54; P < .001 compared with CMB), incomplete resection and metastases (M0R1: HR, 1.86; 95% CI, 1.29 to 2.80; M+: HR, 2.28; 95% CI, 1.50 to 3.46; P < .001 compared with M0R0), and national group were independent prognostic factors for EFS, and OS. The HRs for OS ranged from 0.14 for localized M0 and DNMB/MBEN to 13.67 for metastatic LC/A medulloblastoma in different national groups.

Conclusion

Our results confirm the high frequency of desmoplastic variants of medulloblastomas in early childhood and histopathology as a strong independent prognostic factor. A controlled de-escalation of treatment may be appropriate for young children with DNMB and MBEN in future clinical trials.
Activity of IPI-504, a Novel Heat-Shock Protein 90 Inhibitor, in Patients With Molecularly Defined Non–Small-Cell Lung Cancer
Authors: Sequist Lecia V. , Gettinger Scott , Senzer Neil N. , Martins Renato G. , Jänne Pasi A. , Lilenbaum Rogerio , Gray Jhanelle E. , Iafrate A. John , Katayama Ryohei , Hafeez Nafeeza , Sweeney Jennifer , Walker John R. , Fritz Christian , Ross Robert W. , Grayzel David , Engelman Jeffrey A. , Borger Darrell R. , Paez Guillermo , Natale Ronald
Published: October 2010

Purpose

IPI-504 is a novel, water-soluble, potent inhibitor of heat-shock protein 90 (Hsp90). Its potential anticancer activity has been validated in preclinical in vitro and in vivo models. We studied the activity of IPI-504 after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in patients with advanced, molecularly defined non–small-cell lung cancer (NSCLC).

Patients and Methods

Patients with advanced NSCLC, prior treatment with EGFR TKIs, and tumor tissue available for molecular genotyping were enrolled in this prospective, nonrandomized, multicenter, phase II study of IPI-504 monotherapy. The primary outcome was objective response rate (ORR). Secondary aims included safety, progression-free survival (PFS), and analysis of activity by molecular subtypes.

Results

Seventy-six patients were enrolled between December 2007 and May 2009 from 10 United States cancer centers. An ORR of 7% (five of 76) was observed in the overall study population, 10% (four of 40) in patients who were EGFR wild-type, and 4% (one of 28) in those with EGFR mutations. Although both EGFR groups were below the target ORR of 20%, among the three patients with an ALK gene rearrangement, two had partial responses and the third had prolonged stable disease (7.2 months, 24% reduction in tumor size). The most common adverse events included grades 1 and 2 fatigue, nausea, and diarrhea. Grade 3 or higher liver function abnormalities were observed in nine patients (11.8%).

Conclusion

IPI-504 has clinical activity in patients with NSCLC, particularly among patients with ALK rearrangements.
Looking between Fences in American History
Authors: Streamas John
Published: October 2010

The Smithsonian Institution's traveling extension, its Museum on Main Street program, stops in rural libraries and other public facilities, where local historians and archivists may add their own supplementary exhibits and events. It has been touring Between Fences, an examination of fences in U.S. history. The present study examines a stop in the Community Library in Ketchum, Idaho, in the summer of 2009. Local organizers supplemented the touring material with displays of fences in the history and culture of the U.S. West. These displays, mostly of photographs and paintings, regarded fences bordering ranches and farms as almost natural parts of the landscape. The Smithsonian exhibit, on the other hand, openly acknowledged fences' complicity in issues of public and private ownership. Regrettably, it sidestepped the most contentious aspects of national border issues—Minutemen and xenophobia, for example—but its very foregrounding of fences' history realizes a founding dream of cultural studies.
Adult epidermal Notch activity induces dermal accumulation of T cells and neural crest derivatives through upregulation of jagged 1
Authors: Ambler Carrie A. , Watt Fiona M.
Published: October 2010

Notch signalling regulates epidermal differentiation and tumour formation via non-cell autonomous mechanisms that are incompletely understood. This study shows that epidermal Notch activation via a 4-hydroxy-tamoxifen-inducible transgene caused epidermal thickening, focal detachment from the underlying dermis and hair clumping. In addition, there was dermal accumulation of T lymphocytes and stromal cells, some of which localised to the blisters at the epidermal-dermal boundary. The T cell infiltrate was responsible for hair clumping but not for other Notch phenotypes. Notch-induced stromal cells were heterogeneous, expressing markers of neural crest, melanocytes, smooth muscle and peripheral nerve. Although Slug1 expression was expanded in the epidermis, the stromal cells did not arise through epithelial-mesenchymal transition. Epidermal Notch activation resulted in upregulation of jagged 1 in both epidermis and dermis. When Notch was activated in the absence of epidermal jagged 1, jagged 1 was not upregulated in the dermis, and epidermal thickening, blister formation, accumulation of T cells and stromal cells were inhibited. Gene expression profiling revealed that epidermal Notch activation resulted in upregulation of several growth factors and cytokines, including TNFα, the expression of which was dependent on epidermal jagged 1. We conclude that jagged 1 is a key mediator of non-cell autonomous Notch signalling in skin.
From man to mouse and back again: advances in defining tumor AKTivities in vivo
Authors: Restuccia David F. , Hemmings Brian A.
Published: October 2010

AKT hyperactivation is a common event in human cancers, and inhibition of oncogenic AKT activation is a major goal of drug discovery programs. Mouse tumor models that replicate AKT activation typical of human cancers provide a powerful means by which to investigate mechanisms of oncogenic signaling, identify potential therapeutic targets and determine treatment regimes with maximal therapeutic efficacy. This Perspective highlights recent advances using in vivo studies that reveal how AKT signaling supports tumor formation, cooperates with other mutations to promote tumor progression and facilitates tumor-cell dissemination, focusing on well-characterized prostate carcinoma mouse models that are highly sensitive to AKT activation. The implications of these findings on the therapeutic targeting of AKT and potential new drug targets are also explored.
Reversible transdifferentiation of blood vascular endothelial cells to a lymphatic-like phenotype in vitro
Authors: Cooley Lindsay S. , Handsley Madeleine M. , Zhou Zhigang , Lafleur Marc A. , Pennington Caroline J. , Thompson Erik W. , Pöschl Ernst , Edwards Dylan R.
Published: October 2010

Blood vascular cells and lymphatic endothelial cells (BECs and LECs, respectively) form two separate vascular systems and are functionally distinct cell types or lineages with characteristic gene expression profiles. Interconversion between these cell types has not been reported. Here, we show that in conventional in vitro angiogenesis assays, human BECs of fetal or adult origin show altered gene expression that is indicative of transition to a lymphatic-like phenotype. This change occurs in BECs undergoing tubulogenesis in fibrin, collagen or Matrigel assays, but is independent of tube formation per se, because it is not inhibited by a metalloproteinase inhibitor that blocks tubulogenesis. It is also reversible, since cells removed from 3D tubules revert to a BEC expression profile upon monolayer culture. Induction of the lymphatic-like phenotype is partially inhibited by co-culture of HUVECs with perivascular cells. These data reveal an unexpected plasticity in endothelial phenotype, which is regulated by contact with the ECM environment and/or cues from supporting cells.
CLP-1 associates with MyoD and HDAC to restore skeletal muscle cell regeneration
Authors: Galatioto Josephine , Mascareno Eduardo , Siddiqui M. A. Q.
Published: October 2010

Emerging evidence suggests that eukaryotic gene transcription is regulated primarily at the elongation stage by association and dissociation of the inhibitory protein cardiac lineage protein 1 (CLP-1/HEXIM1) from the positive transcription elongation factor b (P-TEFb) complex. It was reported recently that P-TEFb interacts with skeletal muscle-specific regulatory factor, MyoD, suggesting a linkage between CLP-1-mediated control of transcription and skeletal myogenesis. To examine this, we produced CLP-1 knockdown skeletal muscle C2C12 cells by homologous recombination, and demonstrated that the C2C12 CLP-1 +/− cells failed to differentiate when challenged by low serum in the medium. We also showed that CLP-1 interacts with both MyoD and histone deacetylases (HDACs) maximally at the early stage of differentiation of C2C12 cells. This led us to hypothesize that the association might be crucial to inhibition of MyoD-target proliferative genes. Chromatin immunoprecipitation analysis revealed that the CLP-1/MyoD/HDAC complex binds to the promoter of the cyclin D1 gene, which is downregulated in differentiated muscle cells. These findings suggest a novel transcriptional paradigm whereby CLP-1, in conjunction with MyoD and HDAC, acts to inhibit growth-related gene expression, a requirement for myoblasts to exit the cell cycle and transit to myotubes.
Beyond Signaling and Human Capital: Education and the Revelation of Ability
Authors: Arcidiacono Peter , Bayer Patrick , Hizmo Aurel
Published: October 2010

We provide evidence that college graduation plays a direct role in revealing ability to the labor market. Using the NLSY79, our results suggest that ability is observed nearly perfectly for college graduates, but is revealed to the labor market more gradually for high school graduates. Consequently, from the beginning of their careers, college graduates are paid in accordance with their own ability, while the wages of high school graduates are initially unrelated to their own ability. This view of ability revelation in the labor market has considerable power in explaining racial differences in wages, education, and returns to ability. (JEL D82, I21, I23, J24, J31)
Do Output Contractions Trigger Democratic Change?
Authors: Burke Paul J , Leigh Andrew
Published: October 2010

Does faster economic growth increase pressure for democratic change, or reduce it? Using data for 154 countries for the period 1963–2007, we examine the short-run relationship between economic growth and moves toward and away from greater democracy. To address the potential endogeneity of economic growth, we use variation in precipitation, temperatures, and commodity prices as instruments for a country's rate of economic growth. Our results indicate that more rapid economic growth reduces the short-run likelihood of institutional change toward democracy. Output contractions due to adverse weather shocks appear to have a particularly important impact on the timing of democratic change. (JEL D72, E23, E32, O11, O17, O47)
Determinants of Economic Growth: Will Data Tell?
Authors: Ciccone Antonio , Jarociński Marek
Published: October 2010

Many factors inhibiting and facilitating economic growth have been suggested. Can agnostics rely on international income data to tell them which matter? We find that agnostic priors lead to conclusions that are sensitive to differences across available income estimates. For example, the PWT 6.2 revision of the 1960–1996 income estimates in the PWT 6.1 leads to substantial changes regarding the role of government, international trade, demography, and geography. We conclude that margins of error in international income estimates appear too large for agnostic growth empirics. (JEL O41, O47)
International Competition and Inflation: A New Keynesian Perspective
Authors: Guerrieri Luca , Gust Christopher , López-Salido J. David
Published: October 2010

We develop and estimate an open economy New Keynesian Phillips Curve (NKPC) in which variable demand elasticities give rise to movements in desired markups in response to changes in competitive pressure from abroad. A parametric restriction yields the standard NKPC under constant elasticity and no role for foreign competition to influence domestic inflation. Foreign competition plays an important role in accounting for the behavior of traded goods price inflation. Foreign competition accounted for more than half of a 4 percentage point decline in domestic goods price inflation in the 1990s. Our results also provide evidence against demand curves with a constant elasticity. (JEL E12, E22, E31, F14, F41)
Unmeasured Investment and the Puzzling US Boom in the 1990s
Authors: McGrattan Ellen R , Prescott Edward C
Published: October 2010

For the 1990s, the basic neoclassical growth model predicts a depressed economy, when in fact the US economy boomed. We extend the base model by introducing intangible investment and non-neutral technology change with respect to producing intangible investment goods and find that the 1990s are not puzzling in light of this new theory. There is microeconomic and macroeconomic evidence motivating our extension, and the theory's predictions are in conformity with US national accounts and capital gains. We compare accounting measures with corresponding measures for our model economy and find that standard accounting measures greatly understate the 1990s boom. (JEL E22, E23, O33, O47)
Indications and maternofetal outcome of instrumental deliveries at the University Teaching Hospital of Yaoundé, Cameroon
Authors: Nkwabong E , Nana P N , Mbu R , Takang W , Ekono M R , Kouam L
Published: October 2010

Instrumental deliveries are believed to be associated with increased maternal and, especially, fetal morbidity and mortality. Hence, it is less practiced in many developing countries. The aim of this retrospective study, conducted between 1 January 2007 and 31 December 2008, was to assess the prevalence, indications, neonatal wellbeing and maternal complications of instrumental deliveries. Of 3623 vaginal deliveries, 84 (2.3%) instrumental deliveries were conducted. The most common indication was a prolonged second stage of labour. Fetal wellbeing, measured by the Apgar score, was good and was similar in the group who had forceps delivery and that of the vacuum extraction delivery group. Maternal complications, usually minor, were vaginal and perineal tears. Instrumental delivery should be encouraged and taught in order to reverse the rising caesarean section rate.