bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Associations Between Bioavailable Estradiol and Adipokines in Elderly Women With Different Phenotypes of Obesity
Authors: Tankó László B. , Bruun Jens M. , Alexandersen Peter , Bagger Yu Z. , Richelsen Bjørn , Christiansen Claus , Larsen Philip J.
Published: September 2004

Background—

Peripheral adiposity confers protection against diabetes and atherosclerosis in elderly women. The underlying mechanisms, however, remain to be elucidated.

Methods and Results—

On the basis on dual-energy X-ray absorptiometry measurements of central fat mass (CFM) and peripheral fat mass (PFM), we identified 290 elderly women with distinct forms of body fat distribution (lean, peripheral obesity, central obesity, or general obesity). Study parameters were plasma tumor necrosis factor-α, interleukin (IL)-6, adiponectin, estradiol, sex hormone–binding globulin, insulin resistance, and aortic calcification, graded on lateral radiography. In peripherally and generally obese women, plasma estradiol and insulin resistance were significantly lower, whereas sex hormone–binding globulin and adiponectin were significantly higher compared with centrally obese women independent of age, body mass index, total fat mass, and smoking habits (all
P
<0.05). After adjustment for these confounders, IL-6 in centrally obese women was comparable with that seen in generally obese (similar high CFM%) but significantly higher than in peripherally obese women and lean women (low CFM%). Atherosclerosis was less severe in generally obese (2.5±0.3) compared with centrally obese women (5.0±0.7,
P
=0.001). In multiple regression analysis, total fat mass, body fat distribution, insulin resistance, estradiol, current smoking, treated hyperlipidemia, and treated hypertension contributed independently to the variation of aortic calcification (
R
=0.55, SEE=3.60,
P
<0.001).

Conclusions—

Abundant presence of PFM in generally obese women is associated with increased plasma adiponectin and higher insulin sensitivity, which could explain the apparent protection against the atherogenic effects of IL-6 derived from CFM. Low peripheral exposure to estradiol appears to be a sine qua non of maintained adiponectin secretion from PFM.
Short- and Long-Term Changes in Plasma Inflammatory Markers Associated With Preeclampsia
Authors: Freeman Dilys J. , McManus Frances , Brown Elizabeth Ann , Cherry Lynne , Norrie John , Ramsay Jane E. , Clark Peter , Walker Isobel D. , Sattar Naveed , Greer Ian A.
Published: September 2004

Preeclampsia is characterized by hypertension, dyslipidemia, and increased systemic inflammatory response and has been associated with an increased maternal risk of cardiovascular disease later in life. Low-grade chronic inflammation is a risk factor for cardiovascular disease. This study examined changes in inflammatory markers prospectively during pregnancy, the current inflammatory status of women who had a pregnancy complicated by preeclampsia 20 years previously against matched controls, and the association between inflammatory genes and risk of preeclampsia in a case (n=106) control (n=212) study. In control pregnancies (n=34), mean interleukin-10 (IL-10) levels increased 38% (
P
=0.012) and tumor necrosis factor-α (TNF-α) by 33% (
P
=0.024) between the first and third trimesters. The mean preeclampsia group IL-10 and TNF-α rose by 43% (
P
=0.013 and
P
=0.0065, respectively) from the first to the third trimester. In women with preeclampsia only, plasma IL-6 increased from the first to the third trimester (1.66 [2.04] to 2.94 [2.47] pg/mL;
P
=0.0004). Twenty years after the index pregnancy, women who had had preeclampsia demonstrated significantly higher IL-6 to IL-10 ratio (3.96 [6.07] versus 2.12 [1.89];
P
=0.034) compared with a healthy index pregnancy 20 years previously, that persisted after adjustment for smoking and current body mass index. The IL-1β (C-511T), IL-6 (G-174C), TNF-α (G-308A), E-selectin (S128R), intercellular adhesion molecule-1 (K469E), and C-reactive protein (C1059G) polymorphisms were not associated with risk of developing preeclampsia. In conclusion, preeclampsia is associated with short- and long-term changes in inflammatory status.
Primed Polymorphonuclear Leukocytes, Oxidative Stress, and Inflammation Antecede Hypertension in the Sabra Rat
Authors: Sela Shifra , Mazor Rafi , Amsalam Mazal , Yagil Chana , Yagil Yoram , Kristal Batya
Published: September 2004

Hypertension is accompanied by systemic oxidative stress, inflammation, and priming of peripheral polymorphonuclear leukocytes (PMNLs), yet the involvement of these factors in the pathophysiology of hypertension is incompletely understood. We investigated the relationship between oxidative stress, primed PMNLs, and inflammation and the development of hypertension in the Sabra rat model of salt-sensitive hypertension. Sabra hypertension-resistant rats (SBN/y) (salt-resistant) and Sabra hypertension-prone rats (SBH/y) (salt-sensitive) were studied under normal conditions or during salt loading. Systolic blood pressure (BP) was measured by the tail-cuff method. The extent of oxidative stress was evaluated by the rate of superoxide release from PMNLs, plasma-reduced glutathione (GSH) levels, malondialdehyde (MDA) levels (estimated by thiobarbituric acid–reacting substances), and plasma-carbonylated fibrinogen (Western blotting). Plasma fibrinogen levels and the peripheral PMNL count served as indices of inflammation. In SBH/y and SBN/y provided regular chow without salt loading, BP did not rise above baseline values, yet superoxide release, plasma MDA, carbonylated fibrinogen, and PMNL count were higher in SBH/y than in SBN/y, whereas GSH levels were lower in SBH/y. Four weeks of salt loading resulted in a gradual increase in systolic BP in SBH/y to 205±3 mm Hg, whereas BP remained in SBN/y at baseline normotensive levels. All the parameters reflecting oxidative stress and inflammation were further aggravated with the development of hypertension in salt-loaded SBH/y. We conclude that primed PMNLs, oxidative stress, and inflammation antecede the development of hypertension in this experimental model of hypertension.
Comparison of Four Blood Pressure Indexes for the Prediction of 10-Year Stroke Risk in Middle-Aged and Older Asians
Authors: Miura Katsuyuki , Soyama Yoshiyuki , Morikawa Yuko , Nishijo Muneko , Nakanishi Yumiko , Naruse Yuchi , Yoshita Katsushi , Kagamimori Sadanobu , Nakagawa Hideaki
Published: September 2004

Information has been sparse on the comparison of 4 blood pressure (BP) indexes (systolic BP [SBP], diastolic BP [DBP], pulse pressure [PP], and mean BP [MBP]) in relation to long-term stroke incidence, especially in middle-aged and older Asian people. A prospective cohort study was performed in 4989 Japanese (1523 men and 3466 women) aged 35 to 79 at baseline with 10 years of follow-up. End points included stroke incidence (total, ischemic, and hemorrhagic). Multivariate-adjusted hazard ratios with a 1-SD higher value for each BP index were determined by Cox proportional hazard analyses; Wald χ
2
tests were used to compare the strength of relationships. Analyses were also done for each of 4 age-gender groups consisting of men and women aged 35 to 64 and 65 to 79 years. During follow-up, 132 participants developed stroke. Adjusted hazard ratios for all strokes were 1.68 for SBP, 1.72 for DBP, and 1.80 for MBP, which were higher than that for PP (1.34). SBP and DBP were related positively to stroke risk after adjustment of each other. PP was not the strongest predictor in any age-gender groups among 4 BP indexes. In men aged 65 to 79 years, SBP showed the strongest relationship to all stoke risk (hazard ratio 1.62) among 4 BP indexes. In women aged 65 to 79 years, hazard ratios for all strokes were 2.48 for MBP, 2.46 for DBP, 2.25 for SBP, and 1.57 for PP. The long-term incident stroke risk of high BP in Asians should be assessed by SBP and DBP together, or by MBP, not by PP.
Fluvastatin Enhances the Inhibitory Effects of a Selective AT
1
Receptor Blocker, Valsartan, on Atherosclerosis
Authors: Li Zhen , Iwai Masaru , Wu Lan , Liu Hong-Wei , Chen Rui , Jinno Toyohisa , Suzuki Jun , Tsuda Masahiro , Gao Xin-Yu , Okumura Midori , Cui Tai-Xing , Horiuchi Masatsugu
Published: September 2004

We investigated the effects of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) on the inhibitory effects of an angiotensin II type-1 receptor (AT
1
) blocker on atherosclerosis and explored cellular mechanisms. We gave apolipoprotein E null mice a high-cholesterol diet for 10 weeks and measured atherosclerotic plaque area and lipid deposition. Neither 1 mg/kg per day of valsartan nor 3 mg/kg per day of fluvastatin had any effect on blood pressure or cholesterol concentration; however, both drugs decreased plaque area and lipid deposition after 10 weeks. We then reduced the doses of both drugs to 0.1 mg/kg per day and 1 mg/kg per day, respectively. At these doses, neither drug had an effect on atherosclerotic lesions. When both drugs were combined at these doses, a significant reduction in atherosclerotic lesions was observed. Similar inhibitory effects of valsartan or fluvastatin on the expressions of nicotinamide-adenine dinucleotide/nicotinamide-adenine dinucleotide phosphate oxidase subunits p22
phox
and p47
phox
, production of superoxide anion, the expression of monocyte chemoattractant protein-1, and intercellular adhesion molecule-1 expression were observed. These results suggest that concomitant AT
1
receptor and cholesterol biosynthesis blockade, particularly when given concomitantly, blunts oxidative stress and inflammation independent of blood pressure or cholesterol-related effects.
Omega-3 Fatty Acid Supplementation Augments Sympathetic Nerve Activity Responses to Physiological Stressors in Humans
Authors: Monahan Kevin D. , Wilson Thad E. , Ray Chester A.
Published: September 2004

An inverse relation exists between omega-3 fatty acid intake and risk of cardiovascular disease development/mortality and sudden cardiac death in humans. Mechanisms underlying this cardioprotective effect are unknown, but could involve the autonomic nervous system. We tested the hypothesis that omega-3 fatty acid supplementation (“fish oil”) would reduce muscle sympathetic nerve activity (MSNA) at rest and attenuate increases during physiological stressors. MSNA (peroneal microneurography) was measured during rest, ischemic handgrip to fatigue (IHG), and a cold pressor test (CPT). Measurements were obtained before (PRE) and after (POST) 1 month of daily ingestion of either fish oil (experimental group, n=9) or olive oil capsules (control group, n=9). MSNA at rest was comparable PRE and POST in control (3±1 versus 3±1 bursts/30 seconds) and experimental (4±1 versus 5±1 bursts/30 seconds) subjects. IHG and CPT increased MSNA in both groups PRE and POST. MSNA, arterial blood pressure, and heart rate responses to the stressors were similar PRE and POST in the control group. In contrast, MSNA responses to IHG (Δ4±2 and Δ9±2 bursts/30 seconds;
P
<0.05 for PRE and POST, respectively) and CPT (Δ4±1 versus Δ10±2 bursts/30 seconds;
P
<0.05) were augmented after omega-3 fatty acid supplementation whereas arterial blood pressure and heart rate responses were unchanged. These data indicate that 1 month of omega-3 fatty acid supplementation does not change MSNA at rest but augments sympathetic outflow to physiological stressors. The mechanism underlying augmented MSNA responses to physiological stressors after omega-3 fatty acid supplementation is unknown, but may involve impaired peripheral vasoconstriction.
Torture: from Algiers to Abu Ghraib
Authors: Macmaster Neil
Published: September 2004

The treatment of detainees at Abu Ghraib prison in Iraq focused worldwide media attention on the US practice of torture. Underlying such a practice was not only a self-serving debate in US political circles, academia and entertainment media on how a liberal democracy could justify such methods but also a history of counter-insurgency techniques which owed much to French warfare in Algeria. Yet while the lessons of the torturer have been assiduously learnt, what has been ignored is the recent open debate in France on the profound damage done by such institutionalised barbarity both to the victims and to the individuals and regimes that deploy it.
Britain, the slave trade and slavery, 1808-1843
Authors: Sherwood Marika
Published: September 2004

Britain congratulated itself on having made trading in slaves illegal with the 1807 Act. While later legislation ostensibly strengthened the original Act’s provisions, there were persistent allegations, supported by evidence from the British Foreign and Anti-Slavery society among others, that British companies still profited from it. One of the few prosecutions against the owner of one such company, Pedro Zulueta, ended in his acquittal despite evidence to the contrary. The exploration of the economic, political and social factors underlying both trial and acquittal sheds light on the nineteenth-century British economy’s continuing semi-covert involvement in the trade.
No major association between TGFBR1*6A and prostate cancer
Authors: Kaklamani Virginia , Baddi Lisa , Rosman Diana , Liu Junjian , Ellis Nathan , Oddoux Carole , Ostrer Harry , Chen Yu , Ahsan Habibul , Offit Kenneth , Pasche Boris
Published: September 2004

Prostate cancer is the most commonly diagnosed cancer in men and one of the leading causes of cancer deaths. There is strong genetic evidence indicating that a large proportion of prostate cancers are caused by heritable factors but the search for prostate cancer susceptibility genes has thus far remained elusive. TGFBR1*6A, a common hypomorphic variant of the type I Transforming Growth Factor Beta receptor, is emerging as a tumor susceptibility allele that predisposes to the development of breast, colon and ovarian cancer. The association with prostate cancer has not yet been explored. A total of 907 cases and controls from New York City were genotyped to test the hypothesis that TGFBR1*6A may contribute to the development of prostate cancer. TGFBR1*6A allelic frequency among cases (0.086) was slightly higher than among controls (0.080) but the differences in TGFBR1*6A genotype distribution between cases and controls did not reach statistical significance (p = 0.67). Our data suggest that TGFBR1*6A does not contribute to the development of prostate cancer.
Inter-Platform comparability of microarrays in acute lymphoblastic leukemia
Authors: Mitchell Stephanie A , Brown Kevin M , Henry Michael M , Mintz Michelle , Catchpoole Daniel , LaFleur Bonnie , Stephan Dietrich A
Published: September 2004

Background

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and has been the poster-child for improved therapeutics in cancer, with life time disease-free survival (LTDFS) rates improving from <10% in 1970 to >80% today. There are numerous known genetic prognostic variables in ALL, which include T cell ALL, the hyperdiploid karyotype and the translocations: t(12;21)[TEL-AML1], t(4;11)[MLL-AF4], t(9;22)[BCR-ABL], and t(1;19)[E2A-PBX]. ALL has been studied at the molecular level through expression profiling resulting in un-validated expression correlates of these prognostic indices. To date, the great wealth of expression data, which has been generated in disparate institutions, representing an extremely large cohort of samples has not been combined to validate any of these analyses. The majority of this data has been generated on the Affymetrix platform, potentially making data integration and validation on independent sample sets a possibility. Unfortunately, because the array platform has been evolving over the past several years the arrays themselves have different probe sets, making direct comparisons difficult.

To test the comparability between different array platforms, we have accumulated all Affymetrix ALL array data that is available in the public domain, as well as two sets of cDNA array data. In addition, we have supplemented this data pool by profiling additional diagnostic pediatric ALL samples in our lab. Lists of genes that are differentially expressed in the six major subclasses of ALL have previously been reported in the literature as possible predictors of the subclass.

Results

We validated the predictability of these gene lists on all of the independent datasets accumulated from various labs and generated on various array platforms, by blindly distinguishing the prognostic genetic variables of ALL. Cross-generation array validation was used successfully with high sensitivity and high specificity of gene predictors for prognostic variables. We have also been able to validate the gene predictors with high accuracy using an independent dataset generated on cDNA arrays.

Conclusion

Interarray comparisons such as this one will further enhance the ability to integrate data from several generations of microarray experiments and will help to break down barriers to the assimilation of existing datasets into a comprehensive data pool.
Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a clinical practice guideline
Authors: Malthaner Richard A , Wong Rebecca KS , Rumble R Bryan , Zuraw Lisa ,   members of the Gastrointestinal Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care
Published: September 2004

Background

Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. A clinical practice guideline was developed based on a systematic review investigating neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer.

Methods

A systematic review with meta-analysis was developed and clinical recommendations were drafted. External review of the practice guideline report by practitioners in Ontario, Canada was obtained through a mailed survey, and incorporated. Final approval of the practice guideline was obtained from the Practice Guidelines Coordinating Committee.

Results

The systematic review was developed and recommendations were drafted, and the report was mailed to Ontario practitioners for external review. Ninety percent of respondents agreed with both the evidence summary and the draft recommendations, while only 69% approved of the draft recommendations as a practice guideline. Based on the external review, a revised document was created. The revised practice guideline was submitted to the Practice Guidelines Coordinating Committee for review. All 11 members of the PGCC returned ballots. Eight PGCC members approved the practice guideline report as written and three members approved the guideline conditional on specific concerns being addressed. After these recommended changes were made, the final practice guideline report was approved.

Conclusion

In consideration of the systematic review, external review, and subsequent Practice Guidelines Coordinating Committee revision suggestions, and final approval, the Gastrointestinal Cancer Disease Site Group recommends the following:

For adult patients with resectable thoracic esophageal cancer for whom surgery is considered appropriate, surgery alone (i.e., without neoadjuvant or adjuvant therapy) is recommended as the standard practice.
Immunohistochemical investigations and introduction of new therapeutic strategies in scleromyxoedema: Case report
Authors: Breuckmann Frank , Freitag Marcus , Rotterdam Sebastian , Stuecker Markus , Altmeyer Peter , Kreuter Alexander
Published: September 2004

Background

Scleromyxoedema is a rare chronic skin disease of obscure origin, which may often be associated with severe internal co-morbidity. Even though different casuistic treatment modalities have been described, to date, curing still seems to be impossible.

Case presentation

We report a 44-year-old Caucasian female presenting with remarkable circumscribed, erythematous to skin-coloured, indurated skin eruptions at the forehead, arms, shoulders, legs and the gluteal region. Routine histology and Alcian blue labelling confirmed a massive deposition of acid mucopolysaccharides. Immunohistochemical investigations revealed proliferating fibroblasts and a discrete lymphocytic infiltration as well as increased dermal expression of MIB-1+ and anti-mastcell-tryptase+ cells. Bone marrow biopsies confirmed a monoclonal gammopathy of undetermined significance without morphological characteristics of plasmocytoma; immunofixation unveiled the presence of IgG-kappa paraproteins.

Conclusions

Taking all data into account, our patient exhibited a complex form of lichen mxyoedematosus, which could most likely be linked a variant of scleromyxoedema. Experimental treatment with methotrexate resulted in a stabilisation of clinical symptoms but no improvement after five months of therapy. A subsequent therapeutic attempt by the use of medium-dose ultraviolet A1 cold-light photomonotherapy led to a further stabilisation of clinical symptoms, but could not induce a sustained amelioration of skin condition.
Age related differences in individual quality of life domains in youth with type 1 diabetes
Authors: Wagner Julie A , Abbott Gina , Lett Syretta
Published: September 2004

Background

Investigating individual, as opposed to predetermined, quality of life domains may yield important information about quality of life. This study investigated the individual quality of life domains nominated by youth with type 1 diabetes.

Methods

Eighty young people attending a diabetes summer camp completed the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting interview, which allows respondents to nominate and evaluate their own quality of life domains.

Results

The most frequently nominated life domains were 'family', 'friends', 'diabetes', 'school', and 'health' respectively; ranked in terms of importance, domains were 'religion', 'family', 'diabetes', 'health', and 'the golden rule'; ranked in order of satisfaction, domains were 'camp', 'religion', 'pets', and 'family' and 'a special person' were tied for fifth. Respondent age was significantly positively associated with the importance of 'friends', and a significantly negatively associated with the importance of 'family'. Nearly all respondents nominated a quality of life domain relating to physical status, however, the specific physical status domain and the rationale for its nomination varied. Some respondents nominated 'diabetes' as a domain and emphasized diabetes 'self-care behaviors' in order to avoid negative health consequences such as hospitalization. Other respondents nominated 'health' and focused more generally on 'living well with diabetes'. In an ANOVA with physical status domain as the independent variable and age as the dependent variable, participants who nominated 'diabetes' were younger (M = 12.9 years) than those who nominated 'health' (M = 15.9 years). In a second ANOVA, with rationale for nomination the physical status domain as the independent variable, and age as the dependent variable, those who emphasized 'self care behaviors' were younger (M = 11.8 years) than those who emphasized 'living well with diabetes' (M = 14.6 years). These differences are discussed in terms of cognitive development and in relation to the decline in self-care and glycemic control often observed during adolescence.

Conclusions

Respondents nominated many non-diabetes life domains, underscoring that QOL is multidimensional. Subtle changes in conceptualization of diabetes and health with increasing age may reflect cognitive development or disease adjustment, and speak to the need for special attention to adolescents. Understanding individual quality of life domains can help clinicians motivate their young patients with diabetes for self-care. Future research should employ a larger, more diverse sample, and use longitudinal designs.
Persistent expression of chemokine and chemokine receptor RNAs at primary and latent sites of herpes simplex virus 1 infection
Authors: Cook W James , Kramer Martha F , Walker Russell M , Burwell Timothy J , Holman Holly A , Coen Donald M , Knipe David M
Published: September 2004

Inflammatory cytokines and infiltrating T cells are readily detected in herpes simplex virus (HSV) infected mouse cornea and trigeminal ganglia (TG) during the acute phase of infection, and certain cytokines continue to be expressed at lower levels in infected TG during the subsequent latent phase. Recent results have shown that HSV infection activates Toll-like receptor signaling. Thus, we hypothesized that chemokines may be broadly expressed at both primary sites and latent sites of HSV infection for prolonged periods of time. Real-time reverse transcriptase-polymrease chain reaction (RT-PCR) to quantify expression levels of transcripts encoding chemokines and their receptors in cornea and TG following corneal infection. RNAs encoding the inflammatory-type chemokine receptors CCR1, CCR2, CCR5, and CXCR3, which are highly expressed on activated T cells, macrophages and most immature dendritic cells (DC), and the more broadly expressed CCR7, were highly expressed and strongly induced in infected cornea and TG at 3 and 10 days postinfection (dpi). Elevated levels of these RNAs persisted in both cornea and TG during the latent phase at 30 dpi. RNAs for the broadly expressed CXCR4 receptor was induced at 30 dpi but less so at 3 and 10 dpi in both cornea and TG. Transcripts for CCR3 and CCR6, receptors that are not highly expressed on activated T cells or macrophages, also appeared to be induced during acute and latent phases; however, their very low expression levels were near the limit of our detection. RNAs encoding the CCR1 and CCR5 chemokine ligands MIP-1α, MIP-1β and RANTES, and the CCR2 ligand MCP-1 were also strongly induced and persisted in cornea and TG during the latent phase. These and other recent results argue that HSV antigens or DNA can stimulate expression of chemokines, perhaps through activation of Toll-like receptors, for long periods of time at both primary and latent sites of HSV infection. These chemokines recruit activated T cells and other immune cells, including DC, that express chemokine receptors to primary and secondary sites of infection. Prolonged activation of chemokine expression could provide mechanistic explanations for certain aspects of HSV biology and pathogenesis.
Weekly Epoetin Alfa Maintains Hemoglobin, Improves Quality of Life, and Reduces Transfusion in Breast Cancer Patients Receiving Chemotherapy
Authors: Chang Jose , Couture Felix , Young Scott , McWatters Kara-Lee , Lau Catherine Y.
Published: September 2004

Purpose

Epoetin alfa administered at 40,000 U once weekly (qw) to anemic cancer patients receiving chemotherapy increases hemoglobin levels, improves quality of life (QOL), and reduces transfusions. The benefit of epoetin alfa in maintaining hemoglobin levels in cancer patients with hemoglobin less than 12 g/dL has not been evaluated.

Methods

Breast cancer patients (N = 354) receiving chemotherapy were randomly assigned in 1:1 ratio to epoetin alfa (40,000 U qw) or standard of care (SOC). QOL was assessed at baseline and week 12. Hemoglobin responses, transfusion requirements, and prognostic factors for responses were measured.

Results

At week 12, Functional Assessment of Cancer Therapy–Anemia (FACT–An; mean, 2.16 ± 12.84 for epoetin alfa v −4.43 ± 13.42 for SOC) and FACT–An fatigue (mean, 1.85 ± 10.52 for epoetin alfa v −3.55 ± 11.14 for SOC) change scores were significantly higher in the epoetin alfa group (P < .0001). Hemoglobin responses defined as mean hemoglobin ≥ 12 g/dL or a ≥ 2 g/dL increase compared with baseline were significantly higher in the epoetin alfa group versus SOC: 52.0% v 5.1% and 65.7% v 6.3%, respectively (P < .0001 for both comparisons). Percentage transfused was significantly lower in the epoetin alfa group compared with SOC (8.6% v 22.9%). More than 90% of patients did not require a dose increase and 28.7% had a dose reduction.

Conclusion

Epoetin alfa administered at 40,000 U qw is effective in improving QOL, maintaining hemoglobin level, and reducing transfusion requirements in breast cancer patients. The high effectiveness observed could be attributed in part to early treatment with epoetin alfa.
Effect of Cognitive-Existential Group Therapy on Survival in Early-Stage Breast Cancer
Authors: Kissane David W. , Love Anthony , Hatton Allison , Bloch Sidney , Smith Graeme , Clarke David M. , Miach Patricia , Ikin Jill , Ranieri Nadia , Snyder Raymond D.
Published: September 2004

Purpose

Cognitive-existential group therapy (CEGT) was developed to improve mood and mental attitude toward cancer in women with early-stage breast cancer receiving adjuvant chemotherapy. Given the debate about group therapy's association with increased survival in women with metastatic breast cancer, we were curious to check its effect at a much earlier stage in the cancer journey.

Patients and Methods

We randomly assigned 303 women with early-stage breast cancer who were receiving adjuvant chemotherapy to either 20 sessions of weekly group therapy plus three relaxation classes (n = 154) or to a control condition of three relaxation classes alone (n = 149). The primary outcome was survival.

Results

CEGT did not extend survival; the median survival time was 81.9 months (95% CI, 64.8 to 99.0 months) in the group-therapy women and 85.5 months (95% CI, 67.5 to 103.6 months) in the control arm. The hazard ratio for death was 1.35 (95% CI, 0.76 to 2.39; P = .31). In contrast, histology and axillary lymph node status were significant predictors of survival. Low-grade histology yielded a hazard ratio of 0.342 (95% CI, 0.17 to 0.69), and axillary lymph node–negative status yielded a hazard ratio of 0.397 (95% CI, 0.20 to 0.78).

Conclusion

CEGT does not prolong survival in women with early-stage breast cancer.
A Conceptual Review of Decision Making in Social Dilemmas: Applying a Logic of Appropriateness
Authors: Weber J. Mark , Kopelman Shirli , Messick David M.
Published: September 2004

Despite decades of experimental social dilemma research, “theoretical integration has proven elusive” (Smithson & Foddy, 1999, p. 14). To advance a theory of decision making in social dilemmas, this article provides a conceptual review of the literature that applies a “logic of appropriateness” (March, 1994) framework. The appropriateness framework suggests that people making decisions ask themselves (explicitly or implicitly), “What does a person like me do in a situation like this?” This question identifies 3 significant factors: recognition and classification of the kind of situation encountered, the identity of the individual making the decision, and the application of rules or heuristics in guiding behavioral choice. In contrast with dominant rational choice models, the appropriateness framework proposed accommodates the inherently social nature of social dilemmas, and the role of rule and heuristic based processing. Implications for the interpretation of past findings and the direction of future research are discussed.
Development of a single-dose stabilized poly(d,l-lactic-co-glycolic acid) microspheres-based vaccine against hepatitis B
Authors: Jaganathan K S , Singh Paramjit , Prabakaran D , Mishra Vivek , Vyas Suresh P
Published: September 2004

The purpose of this study was to develop a stable single-dose vaccine based on recombinant hepatitis B surface antigen (HBsAg) in poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres, in which HBsAg was stabilized by a protein stabilizer (trehalose) and an antacid (Mg(OH)2). The microspheres were prepared by the double emulsion method and characterized by scanning electron microscopy. To neutralize the acids liberated by the biodegradable lactic/glycolic acid based polymer, we co-incorporated into the polymer an antacid, Mg(OH)2, which neutralized the acidity during degradation of the polymer and also prevented HBsAg structural losses and aggregation. The antigen integrity after encapsulation was examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by silver staining, isoelectric focusing and Western blotting techniques, which confirmed that antigen remained intact after encapsulation. In-vitro release experiments were performed in phosphate-buffered saline (pH 7.4) and the release of antigen was found to be improved by the protein stabilizer (trehalose). In stability studies, performed at 37°C, the microspheres were found to be stable for 16 days. The immunogenicity of stable microsphere formulations bearing HBsAg was compared with the conventional alum-absorbed HBsAg vaccine in a guinea-pig model. The antibody titre indicated that a single injection of stabilized HBsAg-PLGA microspheres produced a better immune response than two injections of alum-formulated HBsAg vaccine. The findings suggest that recombinant HBsAg can be stabilized by use of a protein stabilizer and antacid during entrapment, and this stabilized preparation can be useful for antigen delivery.
Meeting the challenge: developing systematic reviewing in social policy
Authors: Wallace Alison , Baldwin Sally , Croucher Karen , Quilgars Deborah
Published: September 2004

English

This article uses the experience of reviewing the evidence on the financial support available for defaulting home owners to consider the opportunities and challenges systematic review methods present to social policy. It addresses concerns about examining the strength of given evidence, and perceptions of it being a purely technical method to review existing research. It argues that there is merit in utilising the method to provide research users with transparent summaries of the most robust evidence with minimum bias. The article outlines the challenges presented and suggests that social policy researchers have a valuable contribution to make to the developing methods.
The Latin American pension reform experience: evidence that contradicts discourse
Authors: D'Haeseleer Steven , Berghman Jos
Published: September 2004

English

This article examines the structural pension reforms that have been implemented recently in several Latin American countries. The defining feature of these reforms is the adoption of a privately managed, fully funded pension scheme as a complement or alternative to the public pay-as-you-go system. The article first discusses the relevance of the process of economic globalisation for this particular choice of reform model. It then describes the key design features of the new Latin American pension schemes. Finally, an assessment is offered of the performance of reformed pension systems with respect to their main social functions.
Minimum Incomes for Healthy Living (MIHL): next thrust in UK social policy?
Authors: Morris J.N. , Deeming C.
Published: September 2004

English

Research worldwide is establishing basic needs for personal health and well-being. Official acceptance of this consensual evidence into policy tends to be slow, partial and unsystematic, resulting in avoidable health deficits, waste of human potential and costs to society. Minimum personal costs of meeting these basic needs can be assessed, together with costs of the popular consensus on other requirements for healthy decent participatory living. UK policy could next aim to provide for these costs generally, including the social security and anti-poverty programmes that determine minimum living standards, and so life chances, of increasing millions of people.
Marks of the Beast
Authors: Shuck Glenn W.
Published: September 2004

The Left Behind novels by Tim LaHaye and Jerry Jenkins have become a major publishing phenomenon in recent years. The novels have succeeded in part because they address the anxieties of their readers, using apocalyptic language to depict a future world in which evildoers are punished, and the faithful reverse the tables on their cultural marginality. The novels, however, also speak to the "here and now," articulating in narrative form the beliefs and actions that place one among either the saved or the damned. The novels accomplish this through the issuance of marks. Both believers and the followers of Antichrist have distinctive marks, which prove less than reliable. At stake, ultimately, is an evangelicalism open to the ambiguity and uncertainty of contemporary life, and a reactive fundamentalism that insists, metaphorically, on the rigidity of marks—a quest for certainty ill-advised in a world characterized by relentless change.*
Tracing the Contours of Daoism in North America
Authors: Komjathy Louis
Published: September 2004

ABSTRACT: Utilizing an interpretive model based on "family resem-blances," this paper provides a survey of Daoist teachers and organizations in North America, giving particular attention to those individuals who fall on the "close relations" (Daoist priests, lineage holders) side of the spectrum. The paper first discusses the question of identity with respect to American Daoists. The author advocates the principle of self-identification as an initial methodology, with the additional distinction of Daoist adherents (birthright and convert) and sympathizers. Next, the paper discusses Daoist teachers and organizations in North America via two primary chartological methods: (1) a chronological discussion of the social history of Daoism in North America; and (2) an interpretive framework centering on three models, namely, literati, communal or ritual, and self-cultivation. The author emphasizes that the predominant model in American Daoism centers on self-cultivation, focusing particularly on personal health and healing.*
Perspective: Whither New Religions Studies?
Authors: Bromley David G.
Published: September 2004

New Religions Studies (NRS) is emerging as a new, interdisciplinary area of study in religion. The establishment of a new area of study involves the amassing of a distinctive corpus of knowledge and the construction of organizational auspices for knowledge creation, transmission, and preservation. In this article I identify some components and strategies of successful areas of study and use those as benchmarks for assessing the developmental progress of NRS. Two key organizational units in the development of NRS are universities and professional associations. With respect to knowledge construction, three pivotal components are definitions of the phenomena to be studied, theoretical perspectives in terms of which empirical work is framed, and methodological procedures through which research is conducted. Problems with and prospects for each of these dimensions are explored, with special attention to the issue of definitions.
Effects of re-immunization of heifers against inhibin on hormonal profiles and ovulation rate
Authors: Medan M S , Akagi S , Kaneko H , Watanabe G , Tsonis C G , Taya K
Published: September 2004

To study the effect of re-immunization against inhibin on ovarian response and hormonal profiles, Japanese beef heifers (n= 5) were re-immunized three times with inhibin vaccine (recombinant ovine inhibin α-subunit in oil emulsion, 125 μg ml−1) one year after the primary immunization. Control heifers (n= 5) were injected with placebo (Montanide: Marcol adjuvant alone). Oestrous cycles were synchronized by using prostaglandin F2α(PGF2α) and ovarian response was monitored daily by ultrasonography. Blood samples were collected by jugular venipuncture for assessment of hormonal levels and inhibin antibody titres. In contrast to controls, inhibin re-immunized heifers generated antibodies against inhibin rapidly reaching a peak level 9 days after the first booster injection. The mean concentrations of FSH in re-immunized cows increased significantly in comparison with controls. In addition, there was a significant increase in oestradiol-17β and progesterone levels in re-immunized cows compared with controls. Inhibin re-immunized heifers had a significant increase in small (≥4 < 7 mm), medium (≥7 < 10 mm) and large (≥10 mm in diameter) sized follicles. Moreover, the mean ovulation rate was 5.0 ± 1.1 after the third booster injection in re-immunized heifers compared with control heifers (single ovulation). These results clearly demonstrate that re-immunization of inhibin can be used to enhance ovarian follicular development and ovulation rate. Furthermore, the great number of follicles is a potential source of oocytes that could be harvested forin vitrofertilization and embryo transfer programmes.
Microsatellite Mutation Models
Authors: Sainudiin Raazesh , Durrett Richard T , Aquadro Charles F , Nielsen Rasmus
Published: September 2004

Using genomic data from homologous microsatellite loci of pure AC repeats in humans and chimpanzees, several models of microsatellite evolution are tested and compared using likelihood-ratio tests and the Akaike information criterion. A proportional-rate, linear-biased, one-phase model emerges as the best model. A focal length toward which the mutational and/or substitutional process is linearly biased is a crucial feature of microsatellite evolution. We find that two-phase models do not lead to a significantly better fit than their one-phase counterparts. The performance of models based on the fit of their stationary distributions to the empirical distribution of microsatellite lengths in the human genome is consistent with that based on the human-chimp comparison. Microsatellites interrupted by even a single point mutation exhibit a twofold decrease in their mutation rate when compared to pure AC repeats. In general, models that allow chimps to have a larger per-repeat unit slippage rate and/or a shorter focal length compared to humans give a better fit to the human-chimp data as well as the human genomic data.
Quantitative Trait Loci Affecting Life Span in Replicated Populations of Drosophila melanogaster. II. Response to Selection
Authors: Valenzuela Robert K , Forbes Scott N , Keim Paul , Service Philip M
Published: September 2004

Three selection experiments were used to identify chromosome regions that contain QTL affecting late-life and early-life fitness in Drosophila melanogaster. The selection experiments were initiated by crossing pairs of inbred lines that had been derived from outbred laboratory populations that had different mean life spans. QTL regions were located by association with microsatellite markers that showed significant selection responses. Regions between recombination map positions 54 and 81 on chromosome 2, between 0 and 30 on chromosome 3, and near locations 49 and 81 on chromosome 3 had the strongest support as locations of life-span QTL. There was good general agreement between the life-span QTL regions that were identified by selection and those that were identified in a companion recombination mapping experiment that used the same fly stocks. Many marker loci responded in opposite directions to selection for late- and early-life fitness, indicating negative genetic correlations or trade-offs between those traits. Indirect evidence suggested that some negative genetic correlations were due to antagonistic pleiotropy.
On the Distribution of Temporal Variations in Allele Frequency
Authors: Goldringer Isabelle , Bataillon Thomas
Published: September 2004

The effective population size (Ne) is frequently estimated using temporal changes in allele frequencies at neutral markers. Such temporal changes in allele frequencies are usually estimated from the standardized variance in allele frequencies (Fc). We simulate Wright-Fisher populations to generate expected distributions of Fc and of F̅c (Fc averaged over several loci). We explore the adjustment of these simulated F̅c distributions to a chi-square distribution and evaluate the resulting precision on the estimation of Ne for various scenarios. Next, we outline a procedure to test for the homogeneity of the individual Fc across loci and identify markers exhibiting extreme Fc-values compared to the rest of the genome. Such loci are likely to be in genomic areas undergoing selection, driving Fc to values greater (or smaller) than expected under drift alone. Our procedure assigns a P-value to each locus under the null hypothesis (drift is homogeneous throughout the genome) and simultaneously controls the rate of false positive among loci declared as departing significantly from the null. The procedure is illustrated using two published data sets: (i) an experimental wheat population subject to natural selection and (ii) a maize population undergoing recurrent selection.
Virulence, Multiple Infections and Regulation of Symbiotic Population in the Wolbachia-Asobara tabida Symbiosis
Authors: Mouton Laurence , Dedeine Franck , Henri Hélène , Boulétreau Michel , Profizi Nérina , Vavre Fabrice
Published: September 2004

The density and regulation of microbial populations are important factors in the success of symbiotic associations. High bacterial density may improve transmission to the next generation, but excessive replication could turn out to be costly to the host and result in higher virulence. Moreover, differences in virulence may also depend on the diversity of symbionts. Using the maternally transmitted symbiont Wolbachia, we investigated how bacterial density and diversity are regulated and influence virulence in host insects subject to multiple infection. The model we used was the wasp Asobara tabida that naturally harbors three different Wolbachia strains, of which two are facultative and induce cytoplasmic incompatibility, whereas the third is necessary for the host to achieve oogenesis. Using insect lines infected with different subsets of Wolbachia strains, we show that: (i) some traits of A. tabida are negatively affected by Wolbachia; (ii) the physiological cost increases with the number of co-infecting strains, which also corresponds to an increase in the total bacterial density; and (iii) the densities of the two facultative Wolbachia strains are independent of one another, whereas the obligatory strain is less abundant when it is alone, suggesting that there is some positive interaction with the other strains.
Identification and Characterization of Genes Involved in Embryonic Crystal Cell Formation During Drosophila Hematopoiesis
Authors: Milchanowski Allison B , Henkenius Amy L , Narayanan Maya , Hartenstein Volker , Banerjee Utpal
Published: September 2004

Parallels between vertebrate and Drosophila hematopoiesis add to the value of flies as a model organism to gain insights into blood development. The Drosophila hematopoietic system is composed of at least three classes of terminally differentiated blood cells: plasmatocytes, crystal cells, and lamellocytes. Recent studies have identified transcriptional and signaling pathways in Drosophila involving proteins similar to those seen in human blood development. To identify additional genes involved in Drosophila hematopoiesis, we have conducted a P-element-based genetic screen to isolate mutations that affect embryonic crystal cell development. Using a marker of terminally differentiated crystal cells, we screened 1040 P-element-lethal lines located on the second and third chromosomes and identified 44 individual lines that affect crystal cell development. Identifying novel genes and pathways involved in Drosophila hematopoiesis is likely to provide further insights into mammalian hematopoietic development and disorders.