bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum dots: synthesis, bioapplications, and toxicity
Authors: Valizadeh Alireza , Mikaeili Haleh , Samiei Mohammad , Farkhani Samad Mussa , Zarghami Nosratalah , kouhi Mohammad , Akbarzadeh Abolfazl , Davaran Soodabeh
Published: August 2012

This review introduces quantum dots (QDs) and explores their properties, synthesis, applications, delivery systems in biology, and their toxicity. QDs are one of the first nanotechnologies to be integrated with the biological sciences and are widely anticipated to eventually find application in a number of commercial consumer and clinical products. They exhibit unique luminescence characteristics and electronic properties such as wide and continuous absorption spectra, narrow emission spectra, and high light stability. The application of QDs, as a new technology for biosystems, has been typically studied on mammalian cells. Due to the small structures of QDs, some physical properties such as optical and electron transport characteristics are quite different from those of the bulk materials.
Obesity-related metabolic dysfunction in dogs: a comparison with human metabolic syndrome
Authors: Tvarijonaviciute Asta , Ceron Jose J , Holden Shelley L , Cuthbertson Daniel J , Biourge Vincent , Morris Penelope J , German Alexander J
Published: August 2012

Background

Recently, metabolic syndrome (MS) has gained attention in human metabolic medicine given its associations with development of type 2 diabetes mellitus and cardiovascular disease. Canine obesity is associated with the development of insulin resistance, dyslipidaemia, and mild hypertension, but the authors are not aware of any existing studies examining the existence or prevalence of MS in obese dogs.

Thirty-five obese dogs were assessed before and after weight loss (median percentage loss 29%, range 10-44%). The diagnostic criteria of the International Diabetes Federation were modified in order to define canine obesity-related metabolic dysfunction (ORMD), which included a measure of adiposity (using a 9-point body condition score [BCS]), systolic blood pressure, fasting plasma cholesterol, plasma triglyceride, and fasting plasma glucose. By way of comparison, total body fat mass was measured by dual-energy X-ray absorptiometry, whilst total adiponectin, fasting insulin, and high-sensitivity C-reactive protein (hsCRP) were measured using validated assays.

Results

Systolic blood pressure (P = 0.008), cholesterol (P = 0.003), triglyceride (P = 0.018), and fasting insulin (P < 0.001) all decreased after weight loss, whilst plasma total adiponectin increased (P = 0.001). However, hsCRP did not change with weight loss. Prior to weight loss, 7 dogs were defined as having ORMD, and there was no difference in total fat mass between these dogs and those who did not meet the criteria for ORMD. However, plasma adiponectin concentration was less (P = 0.031), and plasma insulin concentration was greater (P = 0.030) in ORMD dogs.

Conclusions

In this study, approximately 20% of obese dogs suffer from ORMD, and this is characterized by hypoadiponectinaemia and hyperinsulinaemia. These studies can form the basis of further investigations to determine path genetic mechanisms and the health significance for dogs, in terms of disease associations and outcomes of weight loss.
FDG uptake correlates with recurrence and survival after treatment of unresectable stage III non-small cell lung cancer with high-dose proton therapy and chemotherapy
Authors: Xiang Zuo-Lin , Erasmus Jeremy , Komaki Ritsuko , Cox James D , Chang Joe Y
Published: August 2012

Background

We studied whether maximum standardized uptake values (SUV) from [18 F] PET/CT predict clinical outcome after concurrent proton/chemotherapy for stage III non-small cell lung cancer (NSCLC).

Methods

Eighty-four patients were treated prospectively with 74 Gy(RBE) proton therapy and concurrent chemotherapy. PET/CT scans were available before (SUV1) and within 6 months after (SUV2) treatment. The predictive value of clinical and PET/CT factors were analyzed with univariate and multivariate Cox regression models.

Results

Median survival time was 29.9 months. At 3 years, the local recurrence-free survival (LRFS) rate was 34.8%; distant metastasis-free survival (DMFS), 35.4%; progression-free survival (PFS), 31.2%; and overall survival (OS), 37.2%. Patients with SUV2 ≥3.6 (the median) had high rates of LR (p = 0.021). Of 12 clinicopathologic features evaluated in univariate analysis, only KPS, SUV1, and SUV2 predicted LRFS, DMFS, PFS, and OS (p <0.05). Multivariate analysis showed that KPS (p = 0.025) and SUV2 (p = 0.017) were independently prognostic for LRFS and that SUV1, SUV2, and KPS were independently prognostic for DMFS, PFS, and OS (p <0.05).

Conclusions

SUV2 predicted LRFS, and SUV1 and SUV2 predicted DMFS, PFS, and OS, in patients with stage III NSCLC treated with concurrent chemotherapy and high-dose proton therapy.
Association of genetic variation in the NR1H4 gene, encoding the nuclear bile acid receptor FXR, with inflammatory bowel disease
Authors: Attinkara Ragam , Mwinyi Jessica , Truninger Kaspar , Regula Jaroslaw , Gaj Pawel , Rogler Gerhard , Kullak-Ublick Gerd A , Eloranta Jyrki J ,   The Swiss IBD Cohort Study Group
Published: August 2012

Background

Pathogenesis of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), involves interaction between environmental factors and inappropriate immune responses in the intestine of genetically predisposed individuals. Bile acids and their nuclear receptor, FXR, regulate inflammatory responses and barrier function in the intestinal tract.

Methods

We studied the association of five variants (rs3863377, rs7138843, rs56163822, rs35724, rs10860603) of the NR1H4 gene encoding FXR with IBD. 1138 individuals (591 non-IBD, 203 UC, 344 CD) were genotyped for five NR1H4 genetic variants with TaqMan SNP Genotyping Assays.

Results

We observed that the NR1H4 SNP rs3863377 is significantly less frequent in IBD cases than in non-IBD controls (allele frequencies: P = 0.004; wild-type vs. SNP carrier genotype frequencies: P = 0.008), whereas the variant rs56163822 is less prevalent in non-IBD controls (allele frequencies: P = 0.027; wild-type vs. SNP carrier genotype frequencies: P = 0.035). The global haplotype distribution between IBD and control patients was significantly different (P = 0.003). This also held true for the comparison between non-IBD and UC groups (P = 0.004), but not for the comparison between non-IBD and CD groups (P = 0.079).

Conclusions

We show that genetic variation in FXR is associated with IBD, further emphasizing the link between bile acid signaling and intestinal inflammation.
Promising development from translational or perhaps anti‐translational research in breast cancer
Authors: Retsky Michael , Demicheli Romano , Hrushesky William JM , Forget Patrice , De Kock Marc , Gukas Isaac , Rogers Rick A , Baum Michael , Pachmann Katharine , Vaidya Jayant S
Published: August 2012

Background

A great deal of the public's money has been spent on cancer research but demonstrable benefits to patients have not been proportionate. We are a group of scientists and physicians who several decades ago were confronted with bimodal relapse patterns among early stage breast cancer patients who were treated by mastectomy. Since the bimodal pattern was not explainable with the then well‐accepted continuous growth model, we proposed that metastatic disease was mostly inactive before surgery but was driven into growth somehow by surgery. Most relapses in breast cancer would fall into the surgery‐induced growth category thus it was highly important to understand the ramifications of this process and how it may be curtailed. With this hypothesis, we have been able to explain a wide variety of clinical observations including why mammography is less effective for women age 40–49 than it is for women age 50–59, why adjuvant chemotherapy is most effective for premenopausal women with positive lymph nodes, and why there is a racial disparity in outcome.

Methods

We have been diligently looking for new clinical or laboratory information that could provide a connection or correlation between the bimodal relapse pattern and some clinical factor or interventional action and perhaps lead us towards methods to prevent surgery‐initiated tumor activity.

Results

A recent development occurred when a retrospective study appeared in an anesthesiology journal that suggested the perioperative NSAID analgesic ketorolac seems to reduce early relapses following mastectomy. Collaborating with these anesthesiologists to understand this effect, we independently re‐examined and updated their data and, in search of a mechanism, focused in on the transient systemic inflammation that follows surgery to remove a primary tumor. We have arrived at several possible explanations ranging from mechanical to biological that suggest the relapses avoided in the early years do not show up later.

Conclusions

We present the possibility that a nontoxic and low cost intervention could prevent early relapses. It may be that preventing systemic inflammation post surgery will prevent early relapses. This could be controlled by the surgical anesthesiologist's choice of analgesic drugs. This development needs to be confirmed in a randomized controlled clinical trial and we have identified triple negative breast cancer as the ideal subset with which to test this. If successful, this would be relatively easy to implement in developing as well as developed countries and would be an important translational result.
Randomized trial of the effect of intravenous paracetamol on inflammatory biomarkers and outcome in febrile critically ill adults
Authors: Honarmand Hooshyar , Abdollahi Mohammad , Ahmadi Arezoo , Javadi Mohammad Reza , Khoshayand Mohammad Reza , Tabeefar Hamed , Mousavi Sarah , Mahmoudi Laleh , Radfar Mania , Najafi Atabak , Mojtahedzadeh Mojtaba
Published: August 2012

Background and the purpose of the study

The febrile reaction is a complex response involving immunologic and other physiologic systems. Antipyretics are commonly used in critically ill patients with fever. We investigated the inflammatory responses following application of antipyretic therapy in febrile critically ill patients with Systemic Inflammatory Response Syndrome (SIRS).

Patients and methods

In a prospective, randomized controlled study, critically ill patients with fever (T ≥ 38.3°C), SIRS diagnosed within 24 hours of Intensive Care Unit (ICU) admission and Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥10 were randomized into two groups. Upon appearance of fever, one group received intravenous paracetamol 650 mg every 6 hours for 10 days and other group received no treatment unless temperature reached 40°C. Body temperature, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sepsis-related Organ Failure Assessment (SOFA) scores, length of ICU stay, ICU mortality and infectious complications were recorded. Levels of Interleukin-1 alpha (IL-1α), IL-6, IL-10, Tumour Necrosis Factor alpha (TNFα) and High-Sensitive C-Reactive Protein (HS-CRP) were assessed at baseline and 2, 6 and 24 hours after intervention.

Results and discussion

During a period of 15-month screening, 20 patients met the criteria and randomized to the control or paracetamol group. Body temperature decreased significantly in the paracetamol group (p = 0.004) and control group (p = 0.001) after 24 hours, but there was no significant difference between two groups at this time point (p = 0.649). Levels of IL-6 and IL-10 decreased significantly (p = 0.025 and p = 0.047, respectively) in the paracetamol group at 24 hours but this was not of statistical significance in control group. No patterns over time in each group or differences across two groups were found for HS-CRP, TNFα, and IL-1α (p > 0.05). There were no differences regarding ICU length of stay, mortality and infectious complications between both groups.

Conclusion

These results suggest that antipyretic therapy may not be indicated in all ICU patients. Allowing fever to take its natural course does not appear to have detrimental effects on critically ill patients with SIRS and may avoid unnecessary expenses.
Computational genomics-proteomics and Phylogeny analysis of twenty one mycobacterial genomes (Tuberculosis & non Tuberculosis strains)
Authors: Zakham Fathiah , Aouane Othmane , Ussery David , Benjouad Abdelaziz , Ennaji Moulay Mustapha
Published: August 2012

Background

The genus Mycobacterium comprises different species, among them the most contagious and infectious bacteria. The members of the complex Mycobacterium tuberculosis are the most virulent microorganisms that have killed human and other mammals since millennia. Additionally, with the many different mycobacterial sequences available, there is a crucial need for the visualization and the simplification of their data. In this present study, we aim to highlight a comparative genome, proteome and phylogeny analysis between twenty-one mycobacterial (Tuberculosis and non tuberculosis) strains using a set of computational and bioinformatics tools (Pan and Core genome plotting, BLAST matrix and phylogeny analysis).

Results

Considerably the result of pan and core genome Plotting demonstrated that less than 1250 Mycobacterium gene families are conserved across all species, and a total set of about 20,000 gene families within the Mycobacterium pan-genome of twenty one mycobacterial genomes.

Viewing the BLAST matrix a high similarity was found among the species of the complex Mycobacterium tuberculosis and less conservation is found with other slow growing pathogenic mycobacteria.

Phylogeny analysis based on both protein conservation, as well as rRNA clearly resolve known relationships between slow growing mycobacteria.

Conclusion

Mycobacteria include important pathogenic species for human and animals and the Mycobacterium tuberculosis complex is the most cause of death of the humankind. The comparative genome analysis could provide a new insight for better controlling and preventing these diseases.
Effectiveness of rifaximin and fluoroquinolones in preventing travelers’ diarrhea (TD): a systematic review and meta-analysis
Authors: Alajbegovic Sanjin , Sanders John W , Atherly Deborah E , Riddle Mark S
Published: August 2012

Background

Recent developments related to a safe and effective nonabsorbable antibiotic, rifaximin, and identification of postinfectious irritable bowel syndrome as a frequent sequela call for a need to reconsider the value of primary prevention of traveler’s diarrhea (TD) with antibiotics.

Methods

Randomized, placebo-controlled, double-blind studies evaluating the effectiveness and safety of rifaximin or a fluoroquinolone chemoprophylaxis against TD were pooled using a random effects model and assessed for heterogeneity.

Results

The nine studies (four rifaximin and five fluoroquinolone) included resulted in pooled relative risk estimates of 0.33 (95% CI = 0.24–0.45, I
2 = 3.1%) and 0.12 (95% CI = 0.07–0.20, I
2 =0.0%), respectively. Similar rates of treatment emergent adverse events were found between antibiotic and placebo groups.

Conclusions

This meta-analysis supports the effectiveness of antibiotics in preventing TD. However, further studies that include prevention of secondary chronic health outcomes among travelers to different geographic regions, and a formal risk-benefit analysis for antibiotic chemoprophylaxis, are needed.
Tumour morphology of early-onset breast cancers predicts breast cancer risk for first-degree relatives: the Australian Breast Cancer Family Registry
Authors: Dite Gillian S , Makalic Enes , Schmidt Daniel F , Giles Graham G , Hopper John L , Southey Melissa C
Published: August 2012

Introduction

We hypothesised that breast cancer risk for relatives of women with early-onset breast cancer could be predicted by tumour morphological features.

Methods

We studied female first-degree relatives of a population-based sample of 452 index cases with a first primary invasive breast cancer diagnosed before the age of 40 years. For the index cases, a standardised tumour morphology review had been conducted for all; estrogen (ER) and progesterone receptor (PR) status was available for 401 (89%), and 77 (17%) had a high-risk mutation in a breast cancer susceptibility gene or methylation of the BRCA1 promoter region in peripheral blood DNA. We calculated standardised incidence ratios (SIR) by comparing the number of mothers and sisters with breast cancer with the number expected based on Australian incidence rates specific for age and year of birth.

Results

Using Cox proportional hazards modelling, absence of extensive sclerosis, extensive intraductal carcinoma, absence of acinar and glandular growth patterns, and the presence of trabecular and lobular growth patterns were independent predictors with between a 1.8- and 3.1-fold increased risk for relatives (all P <0.02). Excluding index cases with known genetic predisposition or BRCA1 promoter methylation, absence of extensive sclerosis, circumscribed growth, extensive intraductal carcinoma and lobular growth pattern were independent predictors with between a 2.0- and 3.3-fold increased risk for relatives (all P <0.02). Relatives of the 128 (34%) index cases with none of these four features were at population risk (SIR = 1.03, 95% CI = 0.57 to 1.85) while relatives of the 37 (10%) index cases with two or more features were at high risk (SIR = 5.18, 95% CI = 3.22 to 8.33).

Conclusions

This wide variation in risks for relatives based on tumour characteristics could be of clinical value, help discover new breast cancer susceptibility genes and be an advance on the current clinical practice of using ER and PR as pathology-based predictors of familial and possibly genetic risks.
Human suppressive neutrophils CD16bright/CD62Ldim exhibit decreased adhesion
Authors: Kamp Vera M , Pillay Janesh , Lammers Jan-Willem J , Pickkers Peter , Ulfman Laurien H , Koenderman Leo
Published: August 2012

Decrease capture under flow and chemotaxis toward fMLF of human CD16bright/CD62Ldim suppressive neutrophils, compared to CD16bright/CD62Lbright and CD16dim/CD62Lbright neutrophils.

Neutrophils are essential effector cells in host defense against invading pathogens. Regulation of adhesion, migration, and chemotactic processes is important in the homing and activation of these cells. We recently described three distinct subsets of circulating human neutrophils in peripheral blood during acute systemic inflammation. One subset, CD16bright/CD62Ldim, has immune suppressive characteristics because it can inhibit T-cell proliferation. The other two subsets consist of banded CD16dim/CD62Lbright and phenotypically mature (normal) CD16bright/CD62Lbright neutrophils. The current study was designed to determine the adhesion characteristics of these different neutrophil subsets. Analysis of adhesion to activated endothelium under flow conditions revealed that CD16bright/CD62Ldim neutrophils adhered less compared with CD16bright/CD62Lbright and CD16dim/CD62Lbright neutrophils. This decrease in binding capacity could be mimicked in the other neutrophil subsets by blocking L-selectin. Chemotaxis of CD16bright/CD62Ldim neutrophils to the end-target chemoattractant N-formylmethionine-leucine-phenylalanine was lower compared with that for the CD16dim/CD62Lbright neutrophil subset, whereas chemotaxis to cell-derived chemoattractant CXCL8 was comparable. Our data indicate that capture on endothelium under flow conditions, a key mechanism necessary for extravasation, of CD16bright/CD62Ldim neutrophils to inflammatory sites is attenuated, which may facilitate migration of these cells to other tissue localizations. Modulation of this process is a potential target to manipulate inflammation because potentiation of this immune suppression might aid in anti-inflammatory therapy.
Treatment of Pulmonary Metastases in Children With Stage IV Nephroblastoma With Risk-Based Use of Pulmonary Radiotherapy
Authors: Verschuur Arnauld , Tinteren Harm Van , Graf Norbert , Bergeron Christophe , Sandstedt Bengt , de Kraker Jan
Published: August 2012

Purpose

The purpose of this study was to determine the outcome of children with nephroblastoma and pulmonary metastases (PM) treated according to International Society of Pediatric Oncology (SIOP) 93-01 recommendations using pulmonary radiotherapy (RT) in selected patients.

Patients and Methods

Patients (6 months to 18 years) were treated with preoperative chemotherapy consisting of 6 weeks of vincristine, dactinomycin, and epirubicin or doxorubicin. If pulmonary complete remission (CR) was not obtained, metastasectomy was considered. Patients in CR received three-drug postoperative chemotherapy, whereas patients not in CR were switched to a high-risk (HR) regimen with an assessment at week 11. If CR was not obtained, pulmonary RT was mandatory.

Results

Two hundred thirty-four of 1,770 patients had PM. Patients with PM were older (P < .001) and had larger tumor volumes compared with nonmetastatic patients (P < .001). Eighty-four percent of patients were in CR postoperatively, with 17% requiring metastasectomy. Thirty-five patients (16%) had multiple inoperable PM and required the HR protocol. Only 14% of patients received pulmonary RT during first-line treatment. For patients with PM, 5-year event-free survival rate was 73% (95% CI, 68% to 79%), and 5-year overall survival (OS) rate was 82% (95% CI, 77% to 88%). Five-year OS was similar for patients with local stage I and II disease (92% and 90%, respectively) but lower for patients with local stage III disease (68%; P < .001). Patients in CR after chemotherapy only and patients in CR after chemotherapy and metastasectomy had a better outcome than patients with multiple unresectable PM (5-year OS, 88%, 92%, and 48%, respectively; P < .001).

Conclusion

Following the SIOP protocol, pulmonary RT can be omitted for a majority of patients with PM and results in a relatively good outcome.
Meta-Analysis of Cognitive Functioning in Breast Cancer Survivors Previously Treated With Standard-Dose Chemotherapy
Authors: Jim Heather S.L. , Phillips Kristin M. , Chait Sari , Faul Leigh Anne , Popa Mihaela A. , Lee Yun-Hsiang , Hussin Mallory G. , Jacobsen Paul B. , Small Brent J.
Published: August 2012

Purpose

Evidence is mixed regarding long-term cognitive deficits in patients treated with chemotherapy. Previous meta-analyses have not focused specifically on the postchemotherapy period and have not incorporated several recent studies. The goal of the current study was to conduct a meta-analysis of cognitive functioning in breast cancer survivors who were treated with chemotherapy ≥ 6 months previously.

Methods

A search of PubMed, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library yielded 2,751 abstracts, which were independently evaluated by pairs of raters. Meta-analysis was conducted on 17 studies of 807 patients previously treated with standard-dose chemotherapy for breast cancer. Neuropsychological tests were categorized according to eight cognitive domains: attention, executive functioning, information processing, motor speed, verbal ability, verbal memory, visual memory, and visuospatial ability.

Results

Deficits in cognitive functioning were observed in patients treated with chemotherapy relative to controls or prechemotherapy baseline in the domains of verbal ability (g = −0.19; P < .01) and visuospatial ability (g = −0.27; P < .01). Patients treated with chemotherapy performed worse than noncancer controls in verbal ability and worse than patients treated without chemotherapy in visuospatial ability (both P < .01). Age, education, time since treatment, and endocrine therapy did not moderate observed cognitive deficits in verbal ability or visuospatial ability (all P ≥ .51).

Conclusion

Results indicate that, on average, observed cognitive deficits in patients with breast cancer previously treated with chemotherapy are small in magnitude and limited to the domains of verbal ability and visuospatial ability. This information can be used to inform interventions to educate patients with breast cancer regarding the long-term impact of chemotherapy on cognitive functioning.
Aspirin Use and the Risk of Prostate Cancer Mortality in Men Treated With Prostatectomy or Radiotherapy
Authors: Choe Kevin S. , Cowan Janet E. , Chan June M. , Carroll Peter R. , D'Amico Anthony V. , Liauw Stanley L.
Published: August 2012

Purpose

Experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, but clinical data have been limited. We investigated whether use of ACs was associated with the risk of death from prostate cancer.

Patients and Methods

This study comprised 5,955 men in the Cancer of the Prostate Strategic Urologic Research Endeavor database with localized adenocarcinoma of the prostate treated with radical prostatectomy (RP) or radiotherapy (RT). Of them, 2,175 (37%) were receiving ACs (warfarin, clopidogrel, enoxaparin, and/or aspirin). The risk of prostate cancer–specific mortality (PCSM) was compared between the AC and non-AC groups.

Results

After a median follow-up of 70 months, risk of PCSM was significantly lower in the AC group compared with the non-AC group (3% v 8% at 10 years; P < .01). The risks of disease recurrence and bone metastasis were also significantly lower. In a subgroup analysis by clinical risk category, the reduction in PCSM was most prominent in patients with high-risk disease (4% v 19% at 10 years; P < .01). The benefit from AC was present across treatment modalities (RT or RP). Analysis by type of AC medication suggested that the PCSM reduction was primarily associated with aspirin. Multivariable analysis indicated that aspirin use was independently associated with a lower risk of PCSM (adjusted hazard ratio, 0.43; 95% CI, 0.21 to 0.87; P = .02).

Conclusion

AC therapy, particularly aspirin, was associated with a reduced risk of PCSM in men treated with RT or RP for prostate cancer. The association was most prominent in patients with high-risk disease.
Phase II Trial of Cetuximab With or Without Paclitaxel in Patients With Advanced Urothelial Tract Carcinoma
Authors: Wong Yu-Ning , Litwin Samuel , Vaughn David , Cohen Seth , Plimack Elizabeth R. , Lee James , Song Wei , Dabrow Michael , Brody Marion , Tuttle Holly , Hudes Gary
Published: August 2012

Purpose

The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer.

Patients and Methods

Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m2 with or without paclitaxel 80 mg/m2 per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks.

Results

We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases).

Conclusion

Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.
Grizzly Love
Authors: Carman Colin
Published: August 2012

There is a present need in contemporary queer theory to join forces with ecological criticism, specifically with the burgeoning field of animal studies, to critically assess the controversial life and writings of self-proclaimed “eco-warrior” Timothy Treadwell (1957 – 2003). For thirteen summers on Alaska's Katmai coast, Treadwell maintained a dangerous intimacy with a population of grizzly bears, a species of totemic significance with the power, he believed, to both redeem and destroy him. Theoretical works by Jacques Derrida and Donna Haraway help illuminate the vexed power relations between human and animal subjects as well as the queer contours of Treadwell's conservationism. Drawing on his 1997 memoir, Among Grizzlies: Living with Wild Bears in Alaska, as well as film representations of his life's work (principally, Werner Herzog's acclaimed 2005 documentary, Grizzly Man), I ground the queerness of Treadwell's environmentalism in his radical view that Ursus arctos is not exactly nonhuman and therefore capable of loving man in ways that disturb any easy distinction between the “human” and the “animal.” Treadwell's relentless personification of other species is the clearest expression of his queer anthropomorphism, the belief that animals are not only human-like but that humans are irrepressibly animal-like because of their shared sexual nature. Through a highly confessional and sexualized discourse, Treadwell's text registers a sacrificial and masochistic desire to ultimately die for his culture's fantasy of a masculine nature. The article turns finally to the fetishized status of the bear within a sizable gay male subculture known as “bear culture” to align such sexualized iconography with Treadwell's own cross-species identification.
Realizing Rights in Manila
Authors: Thoreson Ryan Richard
Published: August 2012

In recent years, a great deal of scholarly work has focused on global queering and the roles that nongovernmental organizations and activists play in diffusing models of sex and sexuality. With its focus on large-scale phenomena, however, this scholarship has tended to gloss over how those engaged in advocacy actually take up such models. In this essay, I consider the roles that brokers play in shaping LGBT politics in the Philippines: how they engage with transnational frameworks; how this is shaped by history, intersectionality, and heterogeneity; and the extent to which their resulting advocacy might resonate with those it is designed to assist. The introduction of transnational models is not the final stage of the diffusion process; instead, it triggers debates about whether and how to apply those models. While transnational frameworks can drown out local understandings of sex and sexual politics, paying attention to the dynamism of brokerage reveals how they can also be used in powerful and locally resonant ways.
Jonathan Edwards, Affective Conversion, and the Problem of Masochism
Authors: Miller Mark J.
Published: August 2012

This essay uses the work of Jonathan Edwards to trace intellectual, historical, and theoretical connections between eighteenth-century religious conversion in England and New England and later accounts of masochism's Enlightenment philosophical basis. Expanding feminist readings of revival abjection to include racial abjection, I focus on Edwards's account of religious sentiment in a “Personal Narrative” (ca. 1739), A Faithful Narrative of the Surprizing Works of God (1736–37), and Some Thoughts Concerning the Present Revival of Religion in New England (1742). Situating these texts in their philosophical and political contexts, I then use A Treatise Concerning Religious Affections (1746) to show how Edwards's evolving response to revivalist disruptions of hierarchy led him to describe a sentimental structure of desire similar to masochism as a defense against a modern subjectivity that would allow for masochism.
Signalling through mechanical inputs – a coordinated process
Authors: Zhang Huimin , Labouesse Michel
Published: August 2012

There is growing awareness that mechanical forces – in parallel to electrical or chemical inputs – have a central role in driving development and influencing the outcome of many diseases. However, we still have an incomplete understanding of how such forces function in coordination with each other and with other signalling inputs in vivo. Mechanical forces, which are generated throughout the organism, can produce signals through force-sensitive processes. Here, we first explore the mechanisms through which forces can be generated and the cellular responses to forces by discussing several examples from animal development. We then go on to examine the mechanotransduction-induced signalling processes that have been identified in vivo. Finally, we discuss what is known about the specificity of the responses to different forces, the mechanisms that might stabilize cells in response to such forces, and the crosstalk between mechanical forces and chemical signalling. Where known, we mention kinetic parameters that characterize forces and their responses. The multi-layered regulatory control of force generation, force response and force adaptation should be viewed as a well-integrated aspect in the greater biological signalling systems.
Metronidazole treatment for acute phase amoebic liver abscess in patients co-infected with HIV
Authors: Ohnishi K , Uchiyama-Nakamura F
Published: August 2012

Metronidazole is the drug of choice for invasive amoebiasis; however, it is not known whether its dose or duration require modification in HIV infection when treating invasive amoebiasis. Seven HIV-positive patients with acute phase amoebic liver abscess were treated with daily oral administration of 1500 mg of metronidazole for 10 days. None of the patients required abscess drainage, and metronidazole was effective in all patients without serious side-effects. The CD4 cell count or HIV viral load did not appear to influence the efficacy of metronidazole therapy.
Knowledge and attitudes of physicians in private practice towards HIV/AIDS in Mashhad, Iran
Authors: Hedayati-Moghaddam M R , Marjaneh M Moradi , Mashhadi I Eftekharzadeh
Published: August 2012

Being responsible for providing care for HIV/AIDS in a society, physicians should be knowledgeable and have favourable attitudes. We designed a cross-sectional study to assess knowledge and attitudes towards HIV/AIDS of private practicing physicians in Mashhad, Iran. A total of 346 general practitioners and specialists completed anonymous self-administered questionnaires with response rate of 91.1%. For knowledge questions, the mean proportion of correct responses was 53.5% (±13.2). Misconceptions about HIV transmission were the main areas of insufficient knowledge. Surprisingly only 20% knew how to manage a patient who had experienced sexual contact with an HIV-positive partner. While 84% disagreed that ‘HIV-infected individuals deserved to catch infection’ owing to high-risk behaviours, 38% sympathized less with people who were infected via extramarital sex. It seems that knowledge and attitudes towards HIV/AIDS among the studied physicians is not favourable and is an area that requires attention to enable effective management of the disease in Iran.
STIFCompetency: development and evaluation of a new clinical training and assessment programme in sexual health for primary care health professionals
Authors: Hutchinson J , Evans D , Sutcliffe L J , MacQueen R A , Davies J , Estcourt C S
Published: August 2012

UK sexual health services are shifting from hospital-based clinics into primary care, creating a need for high quality clinical sexual health training for non-specialists. Here we describe development, evaluation and costing of a new competency-based training programme, the Sexually Transmitted Infection (STI) Foundation Competency (STIF Competency) programme, based on the Department of Health's toolkit for delivering more specialized sexual health in primary care. We used an action research paradigm with two iterative cycles. Evaluation was to Kirkpatrick's third level with triangulation of results between trainers and trainees, and different methods, including portfolio evaluation, nominal group technique process, semi-structured interviews, Likert questionnaires and chlamydia testing rates. All 13 primary care clinicians completed the training successfully (median 20 hours) and rated STIF Competency highly. Trainers needed to reduce their clinical workload to accommodate the training. Average cost per trainee was £1125, reflecting the need for direct observation of competence across a wide range of clinical skills.
Favourable outcome of progressive multifocal leukoencephalopathy with mefloquine treatment in combination with antiretroviral therapy in an HIV-infected patient
Authors: Adachi E , Koibuchi T , Imai K , Kikuchi T , Koga M , Nakamura H , Miura T , Iwamoto A , Fujii T
Published: August 2012

A 33-year-old man who developed progressive multifocal leukoencephalopathy (PML) with HIV infection is reported. The patient exhibited rapid decline in neurological status after initiation of antiretroviral therapy (ART), which was attributed to the PML-immune re-constitution inflammatory syndrome. Following the administration of mefloquine in combination with ART, the patient's neurological status improved substantially. This case suggests that further investigation of the use of mefloquine might be warranted for treatment of PML in HIV-infected patients.
Access to genitourinary medicine clinics: how long does it take to book an appointment by telephone?
Authors: Dixon K , Thomas M , Ali A H , Patel R , Foley E
Published: August 2012

A unique feature of genitourinary (GU) medicine clinics is that patients can book appointments themselves. The aim of this study was to assess how long it takes and the barriers that exist when making an appointment in a UK GU medicine clinic. Male and female researchers recorded the number of attempts needed to make a successful contact, how the call was dealt with, and the time taken for the call to be initially answered and then completed; 72% (479/666) of the telephone contacts were answered on the first attempt (range: 1–17). The median length of the total call was one minute 51 seconds (range: 15 seconds to eight minutes, six seconds) but male callers took a mean of 40 seconds longer to complete a call ( P < 0.001), reflecting additional and often intrusive questions they were asked compared with female researchers. Care should be taken to ensure that the first point of contact with a clinic is favourable as it reflects on how an entire service may be perceived.
Sexually transmitted infections and sexual behaviour among youth clients of hotel-based female sex workers in Dhaka, Bangladesh
Authors: Haseen F , Chawdhury F A H , Hossain M E , Huq M , Bhuiyan M U , Imam H , Rahman D M M , Gazi R , Khan S I , Kelly R , Ahmed J , Rahman M
Published: August 2012

A cross-sectional study was conducted among youth clients of hotel-based female sex workers (YCHBFSWs) in nine randomly selected hotels in Bangladesh to examine sexual-risk behaviour, condom use and determinants of condom use in last sex, knowledge of HIV, sexually transmitted infection (STI) prevalence and STI care-seeking behaviour. A prestructured questionnaire was used to collect sociodemographic, behavioural, clinical information; urine specimens (before sex) and blood were collected for diagnosis of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, syphilis and herpes simplex virus 2 (HSV2) infection. One thousand and thirteen participants were enroled in the study. Approximately half of them reported visiting female sex workers (FSWs) at least once a month and 25% visited FSWs at least once a week. Only 12% of participants reported regular condom use. The prevalence of N. gonorrhoeae, C. trachomatis, T. vaginalis, syphilis and HSV2 was 2.2%, 3.9%, 7.2%, 2.6% and 12.9%, respectively. Only 15.3% of the YCHBFSW sought STI care in the past year. Negotiation of condom use with FSWs was the main determinant (odds ratio = 17.95) for condom use at last sex. Male clients of FSWs, including YCHBFSW, are an important bridge population for HIV transmission in Bangladesh and HIV interventions should be designed and implemented for them.
Luetic lymphadenopathy despite negative serology
Authors: Drago F , Cinotti E , Tomasini C , Parodi A
Published: August 2012

Laboratory tests can be misleading for the diagnosis of syphilis and false-negative results are possible, but it is rare for both treponemal and non-treponemal tests to prove negative in different stages of the disease. We report on a case of luetic lymphadenopathy, diagnosed by histological examination and supported by immunohistochemical staining for Treponema pallidum, in the absence of skin lesions and positive serology. This case reminds us of how syphilis may present in many different clinical forms and that it should not be excluded only on the basis of negative serological tests. This patient's negative serology was probably due to inadequate initial antibiotic therapy. Given the current widespread use of antibiotics, greater consideration is warranted of the extent to which serological test results are modified by non-specific antibiotic therapies.
A case of lues maligna in an AIDS patient
Authors: Wang H , Wang X , Li S
Published: August 2012

Lues maligna is a severe and rare manifestation of syphilis, also known as malignant syphilis or ulceronodular syphilis and mostly occurring in patients with HIV infection. In this report, we present a case of lues maligna in an AIDS patient. Our report shows the typical clinical features of lues maligna and the important association between lues maligna and HIV/AIDS. Although the clinical manifestations of lues maligna are complicated and severe, the response to the therapy of penicillin is excellent.
High HIV vulnerability of ethnic minorities after a trans-Asian highway construction in remote northern Laos
Authors: Slesak G , Inthalad S , Kim J H , Manhpadit S , Somsavad S , Sisouphanh B , Bouttavong S , Phengsavanh A , Barennes H
Published: August 2012

From 2004 to 2008 a new Asian highway was constructed through remote multiethnic areas of north Laos linking a low with higher HIV prevalence areas in bordering Thailand and China. We assessed the HIV vulnerability in four minority villages alongside the new road in Luang Namtha Province using structured interviews and voluntary counselling and testing (VCT) for HIV. Of 470 villagers aged 15–49 years old, 47.0% did not know any ways of HIV transmission yet 82.1% reported sexual contacts. Median age at first sex was 17.5 years. Sex of never-married 15–24 years old was associated with higher age ( P = 0.002) and ethnicity ( P = 0.013; Hmong odds ratio [OR] 7.27); 61.9% (86/139) used no condom at last non-cohabitant sex, especially women (OR 17.7, P < 0.001) and older villagers ( P = 0.001). No HIV-infection was detected among villagers who received VCT in 2006 (924 of 933) and 2008 (538 of 1249). Nonetheless our findings reveal an alarming vulnerability for HIV among ethnic minorities alongside the new highway, and further culturally adapted prevention efforts are warranted.
Comparative review of imaging methods used for diagnosing renal artery stenosis
Authors: King Deirdre M , Moran Carmel M , Browne Jacinta E
Published: August 2012

This comparative review examines the efficacy of different imaging methods to detect and quantify renal artery stenosis (RAS). Detection of RAS is important because it can lead to renovascular hypertension which is the most common form of secondary hypertension. Furthermore, it is important that a RAS is detected as early as possible as it is a potentially correctable cause of hypertension. 1 If detected at an early stage RAS can potentially be treated using a minimally invasive drug treatment regimen rather than the more invasive percutaneous transluminal renal angioplasty without or with stent placement or surgery. Currently there are a number of different types of modalities used to image the renal artery and determine whether a stenosis is present. Each of these imaging modalities has its own positive and negative aspects, which will be discussed in turn.
A woman's decision to know the sex of her child prior to birth
Authors: Ralph Kimberley , Polson David
Published: August 2012

Introduction

Advances in ultrasound technology have allowed sex determination to be offered to prospective parents during the anomaly scan visit in ultrasound departments. There has been much publicity recently with respect to terminations having been requested based on fetal sex. In other countries there are skewed male to female birth ratios due to ‘wrong sex’ termination, which is usually female. This study has been designed to determine the prevalence of women requesting sex identification and the accuracy of sex determination. Additionally, we have identified demographic and clinical factors, which may be associated with this decision.

Methods

Ethical approval was obtained from the North West Proportionate Review Board. The study included all 2780 women attending their anomaly scan at Salford Royal Hospital in 2009. From their medical records we have determined how many women requested sex identification, the sex that was predicted and the accuracy of this prediction. We also recorded the women's age, parity, race, religion, and past history of fertility problems.

Results

The results showed that 74% of women wanted to know the sex of their baby, of whom 1.8% were unable to be told because of the position of the fetus at the time of the scan. Sex determination was correct in 99.4% of cases and there was no significant difference between the identification of males and females. Factors that were significantly associated with an increased desire to know were, being younger ( < 30 years); multiparous; of Afro Caribbean, Eastern European or Chinese origin [chi squared < 0.05]. Jewish women were the group least likely to request the information (32%), along with women aged 41–47 with fertility problems (42%).

Conclusion

The prevalence, sensitivity and accuracy of ultrasound sex determination have been established in this study and subgroups identified that request this information.
What is Special about Marketing Organic Products? How Organic Assortment, Price, and Promotions Drive Retailer Performance
Authors: Bezawada Ram , Pauwels Koen
Published: August 2012

Higher sales and margins are key goals for retailers promoting emerging products, such as organics, but little is known about their marketing effectiveness and their cross-effects on conventional product sales. Extant research reports conflicting results about price and promotional sensitivity for organic products and does not address the impact of organic assortment. This article calculates long-term own- and cross-elasticities of organic and conventional product sales in response to changes in assortment, price, and promotions. Using a rich data set of 56 categories, the authors test hypotheses on how different costs and benefits of organic products affect these elasticities. They find that enduring actions, such as assortment and regular price changes, have a higher elasticity for organics than for conventional products. In contrast with common wisdom, even “core” organic consumers are sensitive to these actions. Increasing organic assortment and promotion breadth yields higher profits for the total category, as do more frequent promotions on conventional products. The category comparison yields specific advice with regard to where larger assortment and lower prices versus more and deeper promotions are most effective.