bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for house-entry by culicine mosquitoes in a rural town and satellite villages in The Gambia
Authors: Kirby Matthew J , West Philippa , Green Clare , Jasseh Momodou , Lindsay Steve W
Published: November 2008

Background

Screening doors, windows and eaves of houses should reduce house entry by eusynanthropic insects, including the common African house mosquito Culex pipiens quinquefasciatus and other culicines. In the pre-intervention year of a randomized controlled trial investigating the protective effects of house screening against mosquito house entry, a multi-factorial risk factor analysis study was used to identify factors influencing house entry by culicines of nuisance biting and medical importance. These factors were house location, architecture, human occupancy and their mosquito control activities, and the number and type of domestic animals within the compound.

Results

40,407 culicines were caught; the dominant species were Culex thalassius, Cx. pipiens s.l., Mansonia africanus, M. uniformis and Aedes aegypti. There were four times more Cx. pipiens s.l. in Farafenni town (geometric mean/trap/night = 8.1, 95% confidence intervals, CIs = 7.2–9.1) than in surrounding villages (2.1, 1.9–2.3), but over five times more other culicines in the villages (25.1, 22.1–28.7) than in town (4.6, 4.2–5.2). The presence of Cx. pipiens s.l. was reduced in both settings if the house had closed eaves (odds ratios, OR town = 0.62, 95% CIs = 0.49–0.77; OR village = 0.49, 0.33–0.73), but increased per additional person in the trapping room (OR town = 1.16, 1.09–1.24; OR village = 1.10, 1.02–1.18). In the town only, Cx. pipiens s.l. numbers were reduced if houses had a thatched roof (OR = 0.70, 0.51–0.96), for each additional cow tethered near the house (OR = 0.73, 0.65–0.82) and with increasing distance from a pit latrine (OR = 0.97, 0.95–0.99). In the villages a reduction in Cx. pipiens s.l. numbers correlated with increased horses in the compound (OR = 0.90, 0.82–0.99). The presence of all other culicines was reduced in houses with closed eaves (both locations), with horses tethered outside (village only) and with increasing room height (town only), but increased with additional people in the trapping room and where cows were tethered outside (both locations).

Conclusion

The findings of this study advocate eave closure and pit latrine treatment in all locations, and zooprophylaxis using horses in rural areas, as simple control measures that could reduce the number of culicines found indoors.
Chromatin structure and DNA damage repair
Authors: Dinant Christoffel , Houtsmuller Adriaan B , Vermeulen Wim
Published: November 2008

The integrity of the genome is continuously challenged by both endogenous and exogenous DNA damaging agents. These damaging agents can induce a wide variety of lesions in the DNA, such as double strand breaks, single strand breaks, oxidative lesions and pyrimidine dimers. The cell has evolved intricate DNA damage response mechanisms to counteract the genotoxic effects of these lesions. The two main features of the DNA damage response mechanisms are cell-cycle checkpoint activation and, at the heart of the response, DNA repair. For both damage signalling and repair, chromatin remodelling is most likely a prerequisite. Here, we discuss current knowledge on chromatin remodelling with respect to the cellular response to DNA damage, with emphasis on the response to lesions resolved by nucleotide excision repair. We will discuss the role of histone modifications as well as their displacement or exchange in nucleotide excision repair and make a comparison with their requirement in transcription and double strand break repair.
Effect of foot orthoses on lower extremity kinetics during running: a systematic literature review
Authors: McMillan Andrew , Payne Craig
Published: November 2008

Background

Throughout the period of one year, approximately 50% of recreational runners will sustain an injury that disrupts their training regimen. Foot orthoses have been shown to be clinically effective in the prevention and treatment of several running‐related conditions, yet the physical effect of this intervention during running remains poorly understood. The aim of this literature review was therefore to evaluate the effect of foot orthoses on lower extremity forces and pressure (kinetics) during running.

Methods

A systematic search of electronic databases including Medline (1966‐present), CINAHL, SportDiscus, and The Cochrane Library occurred on 7 May 2008. Eligible articles were selected according to pre‐determined criteria. Methodological quality was evaluated by use of the Quality Index as described by Downs & Black, followed by critical analysis according to outcome variables.

Results

The most widely reported kinetic outcomes were loading rate and impact force, however the effect of foot orthoses on these variables remains unclear. In contrast, current evidence suggests that a reduction in the rearfoot inversion moment is the most consistent kinetic effect of foot orthoses during running.

Conclusion

The findings of this review demonstrate systematic effects that may inform the direction of future research, as further evidence is required to define the mechanism of action of foot orthoses during running. Continuation of research in this field will enable targeting of design parameters towards biomechanical variables that are supported by evidence, and may lead to advancements in clinical efficacy.
Aplastic anemia induced disc edema and visual loss in pregnancy: a case report
Authors: Gupta Shailesh K , Brar Vikram S , Keshavamurthy Ravi , Chalam Kakarla V
Published: November 2008

Introduction

A case of aplastic anemia diagnosed during pregnancy, which developed bilateral disc edema and acute pre-retinal hemorrhage leading to vision loss.

Case Presentation

A 20 year old primagravid female developed acute vision loss in her right eye, during hospitalization for treatment of aplastic anemia diagnosed during her pregnancy. Her best-corrected visual acuity (BCVA) was hand motions and fundus evaluation revealed a large pre-macular hemorrhage in the right eye (OD) and bilateral disc edema. Neuro-imaging studies did not reveal any signs of intracranial mass lesion or edema.

Conclusion

There was resolution of the disc edema with improvement in the pre-macular hemorrhage resulting in 20/50 vision in the right eye, following supportive transfusions. Ophthalmic manifestations developing in a pregnant patient with aplastic anemia can be successfully managed with supportive care including red blood cell and platelet transfusions.
Cartilage oligomeric matrix protein deficiency promotes early onset and the chronic development of collagen-induced arthritis
Authors: Geng Hui , Carlsen Stefan , Nandakumar Kutty Selva , Holmdahl Rikard , Aspberg Anders , Oldberg Åke , Mattsson Ragnar
Published: November 2008

Introduction

Cartilage oligomeric matrix protein (COMP) is a homopentameric protein in cartilage. The development of arthritis, like collagen-induced arthritis (CIA), involves cartilage as a target tissue. We have investigated the development of CIA in COMP-deficient mice.

Methods

COMP-deficient mice in the 129/Sv background were backcrossed for 10 generations against B10.Q mice, which are susceptible to chronic CIA. COMP-deficient and wild-type mice were tested for onset, incidence, and severity of arthritis in both the collagen and collagen antibody-induced arthritis models. Serum anti-collagen II and anti-COMP antibodies as well as serum COMP levels in arthritic and wild-type mice were measured by enzyme-linked immunosorbent assay.

Results

COMP-deficient mice showed a significant early onset and increase in the severity of CIA in the chronic phase, whereas collagen II-antibody titers were similar in COMP-deficient and wild-type controls. COMP antibodies were not found in wild-type mice. Finally, COMP-deficient and wild-type mice responded similarly to collagen antibody-induced arthritis, indicating no difference in how collagen II antibodies interact with COMP-deficient cartilage during the initial stages of arthritis.

Conclusions

COMP deficiency enhances the early onset and development of chronic arthritis but does not affect collagen II autoimmunity. These findings accentuate the importance of COMP in cartilage stability.
A comprehensive analysis of prognostic signatures reveals the high predictive capacity of the Proliferation, Immune response and RNA splicing modules in breast cancer
Authors: Reyal Fabien , van Vliet Martin H , Armstrong Nicola J , Horlings Hugo M , de Visser Karin E , Kok Marlen , Teschendorff Andrew E , Mook Stella , van 't Veer Laura , Caldas Carlos , Salmon Remy J , Vijver Marc J van de , Wessels Lodewyk FA
Published: November 2008

Introduction

Several gene expression signatures have been proposed and demonstrated to be predictive of outcome in breast cancer. In the present article we address the following issues: Do these signatures perform similarly? Are there (common) molecular processes reported by these signatures? Can better prognostic predictors be constructed based on these identified molecular processes?

Methods

We performed a comprehensive analysis of the performance of nine gene expression signatures on seven different breast cancer datasets. To better characterize the functional processes associated with these signatures, we enlarged each signature by including all probes with a significant correlation to at least one of the genes in the original signature. The enrichment of functional groups was assessed using four ontology databases.

Results

The classification performance of the nine gene expression signatures is very similar in terms of assigning a sample to either a poor outcome group or a good outcome group. Nevertheless the concordance in classification at the sample level is low, with only 50% of the breast cancer samples classified in the same outcome group by all classifiers. The predictive accuracy decreases with the number of poor outcome assignments given to a sample. The best classification performance was obtained for the group of patients with only good outcome assignments. Enrichment analysis of the enlarged signatures revealed 11 functional modules with prognostic ability. The combination of the RNA-splicing and immune modules resulted in a classifier with high prognostic performance on an independent validation set.

Conclusions

The study revealed that the nine signatures perform similarly but exhibit a large degree of discordance in prognostic group assignment. Functional analyses indicate that proliferation is a common cellular process, but that other functional categories are also enriched and show independent prognostic ability. We provide new evidence of the potentially promising prognostic impact of immunity and RNA-splicing processes in breast cancer.
IL-17 expression by breast-cancer-associated macrophages: IL-17 promotes invasiveness of breast cancer cell lines
Authors: Zhu XingWu , Mulcahy Lori A , Mohammed Rabab AA , Lee Andrew HS , Franks Hester A , Kilpatrick Laura , Yilmazer Acelya , Paish E Claire , Ellis Ian O , Patel Poulam M , Jackson Andrew M
Published: November 2008

Introduction

IL-17 plays an important role in autoimmunity, promoting autoimmunity, inflammation and invasion in multiple sclerosis, rheumatoid arthritis and type I diabetes. The role of IL-17 in cancer is unclear, however, as there are few studies examining IL-17 protein expression in cancer. We therefore examined IL-17 protein expression in human breast cancer and modelled its potential biological significance in vitro.

Methods

Immunohistochemistry was used to determine IL-17 expression in breast cancers. Matrigel invasion assays were employed to examine the effect of IL-17 on cancer cell invasion by a panel of breast cancer cell lines. The role of matrix metalloproteinases (MMPs) was investigated with selective antagonists and immunoassays for MMP-2, MMP-3, MMP-9 and tissue inhibitor of MMP.

Results

IL-17-expressing cells with macrophage morphology were identified in the peritumoural area of a proportion of patients (8/19 patients). Macrophages were confirmed by CD68 staining on serial sections. With the exception of occasional lymphocytes, one patient with rare multinucleate giant cells and one patient with occasional expression of IL-17 in tumour cells, no other IL-17-positive cells were detected. Addition of IL-17 to cell lines in vitro stimulated marked invasion of Matrigel. In contrast, IL-17 did not promote the invasion of MCF7 or T47D cell lines. Invasion was initially thought to be dependent on MMPs, as evidenced by the broad-spectrum MMP inhibitor GM6001 and selective antagonists of MMP-2/MMP-9 and MMP-3. Measurement of MMP-2, MMP-3 and MMP-9, and tissue inhibitor of MMP 1 secretion, failed to reveal any changes in expression following IL-17 exposure. In contrast, TNF promoted secretion of MMPs but IL-17 did not augment TNF, indicating that IL-17 acts via an independent mechanism.

Conclusions

The present study is the first to describe in situ expression of IL-17 protein in human breast tumours and to propose a direct association between IL-17 and breast cancer invasion. The precise effectors of IL-17-dependent invasion remain to be characterised but could include a range of proteases such as a disintegrin and metalloproteinase protein or astacins. Nevertheless, this work identifies a novel potential mechanism for breast cancer invasion and tumour progression, the prognostic implication of which is currently under investigation.
Determinants and impact of multidrug antibiotic resistance in pathogens causing ventilator-associated-pneumonia
Authors: Depuydt Pieter O , Vandijck Dominique M , Bekaert Maarten A , Decruyenaere Johan M , Blot Stijn I , Vogelaers Dirk P , Benoit Dominique D
Published: November 2008

Introduction

The idea that multidrug resistance (MDR) to antibiotics in pathogens causing ventilator-associated pneumonia (VAP) is an independent risk factor for adverse outcome is still debated. We aimed to identify the determinants of MDR versus non-MDR microbial aetiology in VAP and assessed whether MDR versus non-MDR VAP was independently associated with increased 30-day mortality.

Methods

We performed a retrospective analysis of a prospectively registered cohort of adult patients with microbiologically confirmed VAP, diagnosed at a university hospital intensive care unit during a three-year period. Determinants of MDR as compared with non-MDR microbial aetiology and impact of MDR versus non-MDR aetiology on mortality were investigated using multivariate logistic and competing risk regression analysis.

Results

MDR pathogens were involved in 52 of 192 episodes of VAP (27%): methicillin-resistant Staphylococcus aureus in 12 (6%), extended-spectrum β-lactamase producing Enterobacteriaceae in 28 (15%), MDR Pseudomonas aeruginosa and other non-fermenting pathogens in 12 (6%). Multivariable logistic regression identified the Charlson index of comorbidity (odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08 to 1.75, p = 0.01) and previous exposure to more than two different antibiotic classes (OR = 5.11, 95% CI = 1.38 to 18.89, p = 0.01) as predictors of MDR aetiology. Thirty-day mortality after VAP diagnosis caused by MDR versus non-MDR was 37% and 20% (p = 0.02), respectively. A multivariate competing risk regression analysis showed that renal replacement therapy before VAP (standardised hazard ratio (SHR) = 2.69, 95% CI = 1.47 to 4.94, p = 0.01), the Charlson index of comorbidity (SHR = 1.21, 95% CI = 1.03 to 1.41, p = 0.03) and septic shock on admission to the intensive care unit (SHR = 1.86, 95% CI = 1.03 to 3.35, p = 0.03), but not MDR aetiology of VAP, were independent predictors of mortality.

Conclusions

The risk of MDR pathogens causing VAP was mainly determined by comorbidity and prior exposure to more than two antibiotics. The increased mortality of VAP caused by MDR as compared with non-MDR pathogens was explained by more severe comorbidity and organ failure before VAP.
Encapsulated in silica: genome, proteome and physiology of the thermophilic bacterium Anoxybacillus flavithermus WK1
Authors: Saw Jimmy H , Mountain Bruce W , Feng Lu , Omelchenko Marina V , Hou Shaobin , Saito Jennifer A , Stott Matthew B , Li Dan , Zhao Guang , Wu Junli , Galperin Michael Y , Koonin Eugene V , Makarova Kira S , Wolf Yuri I , Rigden Daniel J , Dunfield Peter F , Wang Lei , Alam Maqsudul
Published: November 2008

Background

Gram-positive bacteria of the genus Anoxybacillus have been found in diverse thermophilic habitats, such as geothermal hot springs and manure, and in processed foods such as gelatin and milk powder. Anoxybacillus flavithermus is a facultatively anaerobic bacterium found in super-saturated silica solutions and in opaline silica sinter. The ability of A. flavithermus to grow in super-saturated silica solutions makes it an ideal subject to study the processes of sinter formation, which might be similar to the biomineralization processes that occurred at the dawn of life.

Results

We report here the complete genome sequence of A. flavithermus strain WK1, isolated from the waste water drain at the Wairakei geothermal power station in New Zealand. It consists of a single chromosome of 2,846,746 base pairs and is predicted to encode 2,863 proteins. In silico genome analysis identified several enzymes that could be involved in silica adaptation and biofilm formation, and their predicted functions were experimentally validated in vitro. Proteomic analysis confirmed the regulation of biofilm-related proteins and crucial enzymes for the synthesis of long-chain polyamines as constituents of silica nanospheres.

Conclusions

Microbial fossils preserved in silica and silica sinters are excellent objects for studying ancient life, a new paleobiological frontier. An integrated analysis of the A. flavithermus genome and proteome provides the first glimpse of metabolic adaptation during silicification and sinter formation. Comparative genome analysis suggests an extensive gene loss in the Anoxybacillus/Geobacillus branch after its divergence from other bacilli.
Rock physics modeling of unconsolidated sands: Accounting for nonuniform contacts and heterogeneous stress fields in the effective media approximation with applications to hydrocarbon exploration
Authors: Bachrach Ran , Avseth Per
Published: November 2008

By treating contact stiffness as a variable, one can extend the effective medium approximation used to obtain elastic stiffness of a random pack of spherical grains. More specifically, we suggest calibrating effective media approximation based on contact mechanics by incorporating nonuniform contact models. The simple extension of the theory provides a better fit for many laboratory and field experiments and can provide insight into the micromechanical bonds associated with unconsolidated sediments. This approach is motivated by repeated observations of shear-wave measurements in unconsolidated sands where observed shear-wave velocities are lower than predicted by the Hertz-Mindlin contact theory. We present the calibration process for well-log data from a North Sea well penetrating a shallow-gas discovery and a deepwater well in the Gulf of Mexico. Finally, we demonstrate the benefit of using this model for amplitude variation with angle (AVA) analysis of shallow sand targets in exploration and reservoir studies.
Risk-Adapted Salvage Treatment With Single or Tandem Autologous Stem-Cell Transplantation for First Relapse/Refractory Hodgkin's Lymphoma: Results of the Prospective Multicenter H96 Trial by the GELA/SFGM Study Group
Authors: Morschhauser Franck , Brice Pauline , Fermé Christophe , Diviné Marine , Salles Gilles , Bouabdallah Reda , Sebban Catherine , Voillat Laurent , Casasnovas Olivier , Stamatoullas Aspasia , Bouabdallah Krimo , André Marc , Jais Jean-Philippe , Cazals-Hatem Dominique , Gisselbrecht Christian
Published: November 2008

Purpose

A prospective multicenter trial evaluated a risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation (ASCT) for 245 Hodgkin's lymphoma (HL) patients who experience treatment failure with first-line therapy.

Patients and Methods

Poor-risk patients (150 with primary refractory disease or ≥ two of the following risk factors at first relapse: time to relapse < 12 months, stage III or IV at relapse, and relapse within previously irradiated sites) or intermediate-risk patients (95 with one risk factor at relapse) were eligible for tandem or single ASCT, respectively.

Results

Among poor-risk patients, 105 (70%), including 30 of 55 with cytoreductive chemotherapy-resistant disease, received tandem ASCT, whereas 92 intermediate-risk patients (97%) received single ASCT. According to intent-to-treat analysis, the 5-year freedom from second failure and overall survival (OS) estimates were 73% and 85%, respectively, for the intermediate-risk group and 46% and 57%, respectively, for the poor-risk group. Outcomes were similar for primary refractory and poor-risk/relapsed HL. For patients with chemotherapy-resistant disease, the 46% 5-year OS rate achieved with tandem ASCT compares favorably with the previously reported 30%. Outcomes for partial and complete responders to cytoreduction receiving tandem ASCT did not differ significantly and were better than those previously reported for partial responders receiving single ASCT, but not superior to those reported for complete responders receiving single ASCT. Six poor-risk patients (4%) died from toxicity.

Conclusion

Single ASCT is appropriate for intermediate-risk patients. For poor-risk patients, our results suggest a benefit of tandem ASCT for half of the patients with chemotherapy-resistant disease and partial responders, but not for complete responders to cytoreductive chemotherapy.
Effect of BRCA1 Haplotype on Survival of Non–Small-Cell Lung Cancer Patients Treated With Platinum-Based Chemotherapy
Authors: Kim Hong-Tae , Lee Jong-Eun , Shin Eun-Soon , Yoo Yeon-Kyeong , Cho Jae-Hwa , Yun Min-Hye , Kim Yeul-Hong , Kim Se-Kyu , Kim Hyun-Jung , Jang Tae-Won , Kwak Seung-Min , Kim Chul-Soo , Ryu Jeong-Seon
Published: November 2008

Purpose

To determine whether germ-line variations in BRCA1 affect outcome in non–small-cell lung cancer (NSCLC) patients treated with platinum combination chemotherapy.

Patients and Methods

We evaluated the associations of four tagging BRCA1 polymorphisms and their haplotypes with treatment outcome in 300 NSCLC patients at stages IIIA (16%), IIIB (31%), and IV (53%).

Results

The median age was 63 years (range, 28 to 89 years). Histologically, 139 (46.3%) of the patients had squamous cell carcinomas and 137 (45.7%) had adenocarcinomas. Patient median survival time (MST) was 13.0 months. We observed no significant association between any of the tagging polymorphisms [S1613G, IVS13-1893 (A>C), IVS12-1207 (C>T), and IVS12+112 (C>A)] and overall survival. Of the five haplotypes evaluated (AACC, AACA, GCTC, GATC, and AATC), the survival of patients with two copies of the AACC (wild-type) haplotype was significantly shorter than that of patients with zero to one copies (MST, 8.47 v 14.57 months; log-rank P = .0066), even after adjustment for body weight loss, performance status, stage, second-line treatment, and radiation therapy (hazard ratio = 2.097; 95% CI, 1.339 to 3.284). The survival of patients with squamous cell carcinoma and two copies was significantly shorter than that of other patients with squamous cell carcinoma (MST, 6.8 v 15.3 months; log-rank P = 3.6 × 10−5), whereas differences in survival between the two adenocarcinoma groups was not significant (log-rank P = .677).

Conclusion

These findings suggest that the AACC haplotype of the BRCA1 gene is an important prognostic marker in NSCLC patients treated with platinum combination chemotherapy.
Estrogen Receptor Genotypes Influence Hot Flash Prevalence and Composite Score Before and After Tamoxifen Therapy
Authors: Jin Yan , Hayes Daniel F. , Li Lang , Robarge Jason D. , Skaar Todd C. , Philips Santosh , Nguyen Anne , Schott Anne , Hayden Jill , Lemler Suzanne , Storniolo Anna Maria , Flockhart David A. , Stearns Vered
Published: November 2008

Purpose

Hot flashes are common and frequently lead to drug discontinuation among women prescribed tamoxifen. We determined whether genetic polymorphisms in estrogen receptors (ESRs) α and β (ESR1 and ESR2, respectively) are associated with tamoxifen-induced hot flashes.

Patients and Methods

We determined ESR1 PvuII and XbaI and ESR2-02 genotypes in 297 women who were initiating tamoxifen. One-week hot flash diaries were collected to calculate a hot flash score (frequency × severity) before and 1, 4, 8, and 12 months after starting tamoxifen.

Results

Approximately 80% of 297 participants reported hot flashes before or during the first year of tamoxifen. After 4 months of tamoxifen, premenopausal women who did not receive adjuvant chemotherapy had a four-fold increase in hot flash score (from 5.9 to 23.6; P = .003) compared with a 1.17-fold increase (from 19.6 to 23; P = .34) in those who received chemotherapy. In premenopausal women, increased number of ESR1 PvuII and XbaI CG alleles was associated with higher baseline hot flash scores compared with those who had other haplotypes (P = .0026). At 4 months, postmenopausal women with ESR1 PvuII CC and ESR2-02 GG genotypes had 4.6 times increases in hot flash scores than other postmenopausal women (56 v 12; P = .0007). Women who had the ESR2-02 AA genotype were significantly less likely to experience tamoxifen-induced hot flashes than women who carried at least one ESR-02 G allele (hazard ratio, 0.26; 95% CI, 0.10 to 0.63; P = .001).

Conclusion

Knowledge of menopausal status, prior chemotherapy, and ESR genotype may help predict which women are most likely to suffer hot flashes during tamoxifen treatment.
Plasma Isoflavones and Subsequent Risk of Prostate Cancer in a Nested Case-Control Study: The Japan Public Health Center
Authors: Kurahashi Norie , Iwasaki Motoki , Inoue Manami , Sasazuki Shizuka , Tsugane Shoichiro
Published: November 2008

Purpose

The incidence of prostate cancer is much lower in Japanese than Western populations. Given the preventive effects of isoflavones on carcinogenesis in the prostate in many nonhuman studies and the high consumption of isoflavones in Japanese, this low incidence may be partly due to the effects of soy.

Patients and Methods

We conducted a nested case-control study within the Japan Public Health Center–based Prospective Study. A total of 14,203 men aged 40 to 69 years who had returned the baseline questionnaire and provided blood samples were observed from 1990 to 2005. During a mean of 12.8 years of follow-up, 201 newly diagnosed prostate cancers were identified. Two matched controls for each case were selected from the cohort. Conditional logistic regression model was used to estimate the odds ratios (ORs) and 95% CIs for prostate cancer in relation to plasma levels of isoflavone.

Results

Plasma genistein level tended to be inversely associated with the risk of total prostate cancer. Although plasma daidzein showed no association, the highest tertile for plasma equol, a metabolite of daidzein, was significantly associated with a decreased risk of total prostate cancer (OR = 0.60; 95% CI, 0.36 to 0.99; Ptrend= .04). These inverse associations were strengthened after analysis was confined to localized cases, with ORs in the highest group of plasma genistein and equol compared with the lowest of 0.54 (95% CI, 0.29 to 1.01; Ptrend= .03) and 0.43 (95% CI, 0.22 to 0.82; Ptrend= .02), respectively. Plasma isoflavone levels were not statistically significantly associated with the risk of advanced prostate cancer.

Conclusion

Isoflavones may prevent the development of prostate cancer.
Predictive Model for Survival in Patients With Advanced Cancer
Authors: Chow Edward , Abdolell Mohamed , Panzarella Tony , Harris Kristin , Bezjak Andrea , Warde Padraig , Tannock Ian
Published: November 2008

Purpose

To derive and validate a simple predictive model for survival of patients with metastatic cancer attending a palliative radiotherapy clinic.

Patients and Methods

We described previously a model predicting survival of patients referred for palliative radiotherapy using six prognostic factors: primary cancer site, site of metastases, Karnofsky performance score (KPS), and the fatigue, appetite, and shortness of breath subscales from the Edmonton Symptom Assessment Scale. Here we simplified the model to include only three factors: primary cancer site, site of metastases, and KPS. Each factor was assigned a value proportional to its prognostic weight, and the weighted scores for each patient were summed to obtain a survival prediction score (SPS). Patients were also grouped according to their number of risk factors (NRF): nonbreast cancer, metastases other than bone, and KPS ≤ 60. The three- and six- variable models were evaluated for their ability to predict survival in patients referred during a different time period and of those referred to a different cancer center.

Results

A training set of 395 patients, a temporal validation set of 445 patients, and an external validation set of 467 patients were used. The ability of the three- and six-variable models to separate patients into three prognostic groups and to predict their survival was similar using both SPS and NRF methods in the training, temporal, and external validation data sets. There was no statistically significant difference in the performance of the models.

Conclusion

The three-variable NRF model is preferred because of its relative simplicity.
American Society of Clinical Oncology 2008 Clinical Practice Guideline Update: Use of Chemotherapy and Radiation Therapy Protectants
Authors: Hensley Martee L. , Hagerty Karen L. , Kewalramani Tarun , Green Daniel M. , Meropol Neal J. , Wasserman Todd H. , Cohen Gary I. , Emami Bahman , Gradishar William J. , Mitchell R. Brian , Thigpen J. Tate , Trotti Andy , von Hoff Daniel , Schuchter Lynn M.
Published: November 2008

Purpose

To update a clinical practice guideline on the use of chemotherapy and radiation therapy protectants for patients with cancer.

Methods

An update committee reviewed literature published since the last guideline update in 2002.

Results

Thirty-nine reports met the inclusion criteria: palifermin and dexrazoxane, three reports (two studies) each; amifostine, 33 reports (31 studies); and mesna, no published randomized trials identified since 2002.

Recommendations

Dexrazoxane is not recommended for routine use in breast cancer (BC) in adjuvant setting, or metastatic setting with initial doxorubicin-based chemotherapy. Consider use with metastatic BC and other malignancies, for patients who have received more than 300 mg/m2 doxorubicin who may benefit from continued doxorubicin-containing therapy. Cardiac monitoring should continue in patients receiving doxorubicin. Amifostine may be considered for prevention of cisplatin-associated nephrotoxicity, reduction of grade 3 to 4 neutropenia (alternative strategies are reasonable), and to decrease acute and late xerostomia with fractionated radiation therapy alone for head and neck cancer. It is not recommended for protection against thrombocytopenia, prevention of platinum-associated neurotoxicity or ototoxicity or paclitaxel-associated neuropathy, prevention of radiation therapy–associated mucositis in head and neck cancer, or prevention of esophagitis during concurrent chemoradiotherapy for non–small-cell lung cancer. Palifermin is recommended to decrease severe mucositis in autologous stem-cell transplantation (SCT) for hematologic malignancies with total-body irradiation (TBI) conditioning regimens, and considered for patients undergoing myeloablative allogeneic SCT with TBI-based conditioning regimens. Data are insufficient to recommend use in the non-SCT setting.
Peptidylarginine deiminase 2 (PAD2) overexpression in transgenic mice leads to myelin loss in the central nervous system
Authors: Musse Abdiwahab A. , Li Zhen , Ackerley Cameron A. , Bienzle Dorothee , Lei Helena , Poma Roberto , Harauz George , Moscarello Mario A. , Mastronardi Fabrizio G.
Published: November 2008

Demyelination in the central nervous system is the hallmark feature in multiple sclerosis (MS). The mechanism resulting in destabilization of myelin is a complex multi-faceted process, part of which involves deimination of myelin basic protein (MBP). Deimination, the conversion of protein-bound arginine to citrulline, is mediated by the peptidylarginine deiminase (PAD) family of enzymes, of which the PAD2 and PAD4 isoforms are present in myelin. To test the hypothesis that PAD contributes to destabilization of myelin in MS, we developed a transgenic mouse line (PD2) containing multiple copies of the cDNA encoding PAD2, under the control of the MBP promoter. Using previously established criteria, clinical signs were more severe in PD2 mice than in their normal littermates. The increase in PAD2 expression and activity in white matter was demonstrated by immunohistochemistry, reverse transcriptase-PCR, enzyme activity assays, and increased deimination of MBP. Light and electron microscopy revealed more severe focal demyelination and thinner myelin in the PD2 homozygous mice compared with heterozygous PD2 mice. Quantitation of the disease-associated molecules GFAP and CD68, as measured by immunoslot blots, were indicative of astrocytosis and macrophage activation. Concurrently, elevated levels of the pro-inflammatory cytokine TNF-α and nuclear histone deimination support initiation of demyelination by increased PAD activity. These data support the hypothesis that elevated PAD levels in white matter represents an early change that precedes demyelination.
Conceptions of learning, approaches to studying and personal development in UK higher education
Authors: Edmunds Robert , Richardson John T. E.
Published: November 2008

Background Students in higher education are known to vary in their conceptions of learning, their approaches to studying, and the personal development and personal change that result.

Aims This study aimed to explore the relationships among these four aspects of students' experience; to examine whether there were variations across academic subjects and across departments in each subject; and to explore whether there were changes from first year to after graduation.

Sample Students in the first year and the final year of the undergraduate programmes at 15 departments, five offering each of three subjects: bioscience, business studies, and sociology.

Method Participants completed a questionnaire containing four instruments and were given a similar questionnaire roughly two years later (when the entering students were in their third year, and when the exiting students were in their second year after graduation).

Results The students' conceptions of learning showed a clear relationship with their approaches to studying, but the relationships with their personal development and personal change were much weaker. The students' scores were significantly related to age and gender and showed some significant differences across academic subjects and departments. However, there was little change in their scores over time.

Conclusion Students' approaches to studying are influenced by their conceptions of learning and are relatively consistent across different contexts. In contrast, their reports of personal change and development seem to be determined by their implicit theories on entering higher education.
Equivalence of the statistics for replicability and area under the ROC curve
Authors: Irwin R. John
Published: November 2008

Two statistics, one recent and one well known, are shown to be equivalent. The recent statistic, prep, gives the probability that the sign of an experimental effect is replicable by an experiment of equal power. That statistic is equivalent to the well‐known measure for the area under a receiver operating characteristic (ROC) curve for statistical power against significance level. Both statistics can be seen as exemplifying the area theorem of psychophysics.
Book Reviews
Authors: Sevdalis Nick
Published: November 2008

Understanding statistics in the behavioural sciences Bakeman R. Robinson B. F. Mahwah, NJ and London: Erlbaum 2005, Price HB: £39.95 ISBN HB: 0‐8058‐4944‐0 (Contains CD)
Producing expertise and achieving attribution in the context of computer support
Authors: Quayle Michael , Durrheim Kevin
Published: November 2008

This study uses transcripts of interactions recorded between computer technicians and users to investigate the activities related to attribution and problem solving in the context of institutional computer support. We explore how achieving consensual attributions (in the context of diagnosis) is integral to managing moment‐to‐moment social demands, and how the outcomes are subject to negotiations about the definition of the problem and the nature of the social contract between interactants. We also show that these immediate interactional interests are subject to the longer‐term ‘moral careers’ of the participants which are themselves subject to the roles, obligations, and concerns that participants have by virtue of their social and institutional positions. These immediate and longer‐term layers of concern are interrelated and contingent, and all are important elements of how consensual attributions are socially accomplished in this context.
Smoking in the lived world: How young people make sense of the social role cigarettes play in their lives
Authors: Fry Gary , Grogan Sarah , Gough Brendan , Conner Mark
Published: November 2008

This qualitative study explored how young people (16‐ to 24‐year olds), both smokers and non‐smokers, talk about the social role of smoking in their everyday lives. In 22 focus group interviews, 47 high school children and 40 university undergraduates participated. On the basis of analyses, it is proposed that the perceived need to smoke cannot be reduced to addiction; cigarettes appear to play a complex social role in young people's lives. In order to resist smoking, participants highlighted the need to provide an excuse to peers, and some reasons (e.g. an interest in sport for boys) were considered more legitimate than others. Cigarettes (certain brands) were also claimed to be used as a way of controlling other people's perception of smokers, and also to serve as a social tool (for instance, to fill in awkward gaps in conversation). Additionally, smoking was argued to be subject to context (e.g. some schools possess a pro‐smoking ethic, while others and universities are anti‐smoking). Finally, it was claimed that stopping smoking is difficult since all of the foregoing social factors cannot easily be avoided. The findings of this study compliment and enrich existing social psychological approaches to smoking in young people, and lay the basis for anti‐smoking campaigns which take into account the complex social role cigarettes play in the lives of young people.
Sex differences in the structure and stability of children's playground social networks and their overlap with friendship relations
Authors: Baines Ed , Blatchford Peter
Published: November 2008

Gender segregated peer networks during middle childhood have been highlighted as important for explaining later sex differences in behaviour, yet few studies have examined the structural composition of these networks and their implications. This short‐term longitudinal study of 119 children (7–8 years) examined the size and internal structure of boys' and girls' social networks, their overlap with friendship relations, and their stability over time. Data collection at the start and end of the year involved systematic playground observations of pupils' play networks during team and non‐team activities and measures of friendship from peer nomination interviews. Social networks were identified by aggregating play network data at each time point. Findings showed that the size of boy's play networks on the playground, but not their social networks, varied according to activity type. Social network cores consisted mainly of friends. Girl's social networks were more likely to be composed of friends and boys' networks contained friends and non‐friends. Girls had more friends outside of the social network than boys. Stability of social network membership and internal network relations were higher for boys than girls. These patterns have implications for the nature of social experiences within these network contexts.
Appeal of organizational values is in the eye of the beholder: The moderating role of employee identity
Authors: Johnson Russell E. , Jackson Erin M.
Published: November 2008

This study examined the effects of organizational values on employee attachment. Factor analytic results across two studies indicated that organizational values cluster into interdependent and independent factors. In Study 2, organizational values data were collected from supervisors, and identity and attachment data were collected from subordinates. As predicted, relationships involving interdependent and dependent values were contingent on employee identity. Specifically, interdependent organizational values predicted turnover cognition and organizational commitment for employees who reported strong collective identities. Independent organizational values, on the other hand, predicted the commitment of employees with strong individual identities. Implications of these results and directions for future research are discussed.
Inhibiting Dickkopf-1 (Dkk1) Removes Suppression of Bone Formation and Prevents the Development of Osteolytic Bone Disease in Multiple Myeloma
Authors: Heath Deborah J , Chantry Andrew D , Buckle Clive H , Coulton Les , Shaughnessy John D , Evans Holly R , Snowden John A , Stover David R , Vanderkerken Karin , Croucher Peter I
Published: November 2008

Multiple myeloma (MM) is associated with the development of osteolytic bone disease, mediated by increased osteoclastic bone resorption and impaired osteoblastic bone formation. Dickkopf-1 (Dkk1), a soluble inhibitor of wingless/int (Wnt) signaling and osteoblastogenesis, is elevated in patients with MM and correlates with osteolytic bone disease. In this study, we investigated the effect of inhibiting Dkk1 on the development of osteolytic lesions in the 5T2MM murine model of myeloma. We showed that Dkk1 is expressed by murine 5T2MM myeloma cells. Injection of 5T2MM cells into C57BL/KaLwRij mice resulted in the development of osteolytic bone lesions (p < 0.05), mediated by increased osteoclast numbers (p < 0.001) and a decrease in osteoblast numbers (p < 0.001) and mineralizing surface (p < 0.05). Mice bearing 5T2MM cells were treated with an anti-Dkk1 antibody (BHQ880, 10 mg/kg, IV, twice weekly for 4 wk) from time of paraprotein detection. Anti-Dkk1 treatment prevented 5T2MM-induced suppression of osteoblast numbers (p < 0.001) and surface (p < 0.001). Treatment increased mineralizing surface by 28% and bone formation rate by 25%; however, there was no change in mineral apposition rate. Inhibiting Dkk1 had no effect on osteoclast numbers. μCT analysis showed that anti-Dkk1 treatment significantly protected against 5T2MM-induced trabecular bone loss (p < 0.05) and reduced the development of osteolytic bone lesions (p < 0.05). Treatment had no significant effect on tumor burden. These data suggest that inhibiting Dkk1 prevents the suppression of bone formation and in doing so is effective in preventing the development of osteolytic bone disease in myeloma, offering an effective therapeutic approach to treating this clinically important aspect of myeloma.
Somatic Mutations in SQSTM1 Detected in Affected Tissues From Patients With Sporadic Paget's Disease of Bone
Authors: Merchant Anand , Smielewska Magda , Patel Nimit , Akunowicz Jennifer D , Saria Elizabeth A , Delaney John D , Leach Robin J , Seton Margaret , Hansen Marc F
Published: November 2008

Paget's disease of bone (PDB) is a focal disorder of bone remodeling that leads to overgrowth of affected bone, with rare progression to osteosarcoma. Extensive studies of familial PDB showed that a majority of cases harbor germline mutations in the Sequestosome1 gene (SQSTM1). In contrast, little is known about the mutational status of SQSTM1 in sporadic PDB. We hypothesized that somatic SQSTM1 mutations might occur in the affected tissues of sporadic PDB and pagetic osteosarcoma. We used laser capture microdissection to capture homogeneous populations of cells from the affected bone or tumor of patients with sporadic PDB or pagetic osteosarcoma, respectively. DNA from these samples and appropriate controls was used for sequence analysis and allelic discrimination analysis. Two of five patients with sporadic PDB had SQSTM1C1215T mutations detected in their affected bone but not in their blood samples, indicating a somatic origin of the mutations. Samples from three of five sporadic pagetic osteosarcoma patients had the SQSTM1C1215T mutation, whereas the normal adjacent tissue from two of these tumors clearly lacked the mutation, again indicating an occurrence of somatic events. No SQSTM1 mutations were found in primary adolescent osteosarcomas. The discovery of somatic SQSTM1 mutations in sporadic PDB and pagetic osteosarcoma shows a role for SQSTM1 in both sporadic and inherited PDB. The discovery of somatically acquired mutations in both the diseased bone and tumor samples suggests a paradigm shift in our understanding of this disease.
Association Analysis of WNT10B With Bone Mass and Structure Among Individuals of African Ancestry
Authors: Zmuda Joseph M , Yerges Laura M , Kammerer Candace M , Cauley Jane A , Wang Xiaojing , Nestlerode Cara S , Wheeler Victor W , Patrick Alan L , Bunker ClareAnn H , Moffett Susan P , Ferrell Robert E
Published: November 2008

Wnts comprise a family of secreted growth factors that regulate the development and maintenance of many organs. Recently, Wnt10b was shown to stimulate osteoblastogenesis and bone formation in mice. To evaluate further the role of Wnt10b in bone health in humans, we performed bidirectional sequencing of ∼8 kb of the WNT10B gene region in 192 individuals (96 African, 96 white) to identify single nucleotide polymorphisms (SNPs). We identified 19 SNPs with minor allele frequency (MAF) ≥0.01. Ten of these SNPs were not present in the NCBI dbSNP database (build 127), whereas 10 of the 20 SNPs (50%) reported in dbSNP were not verified. We initially genotyped seven tagging SNPs that captured common (MAF ≥ 0.05) variation in the region with r2 > 0.80 and a potentially functional SNP in exon 5 in 1035 Afro-Caribbean men ≥40 yr of age. Association analysis showed three SNPs in a 3′ region of linkage disequilibrium that were associated with DXA measures of hip BMD. Associations between two of these three SNPs (rs1051886, rs3741627) with hip BMD were replicated in an additional 980 Afro-Caribbean men (p < 0.05), in the combined sample of 2015 men (p ≤ 0.006), and in 416 individuals ≥18 yr of age (mean, 44 yr) belonging to eight extended, multigenerational Afro-Caribbean families with mean family size >50 (3535 relative pairs; p < 0.05). Further analysis showed that rs1051886 and rs3741627 were associated with cortical cross-sectional area, periosteal circumference, and BMC in the radius, such that individuals with the minor alleles had lower biomechanical indices of long-bone bending strength. This analysis implicates the WNT10B locus as a genetic element in the regulation of bone mass and structural geometry.