bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytomegalovirus shedding in the oral cavity of allogeneic haematopoietic stem cell transplant patients
Authors: Correia‐Silva JdeF , Victória JMN , Guimarães ALS , Salomão UE , De Abreu MHNG , Bittencourt H , Gomez RS
Published: January 2007

Objective:  This study was designed to investigate the effect of allogeneic haematopoietic stem cell transplantation (HSCT) on cytomegalovirus (CMV) shedding in the saliva by nested polymerase chain reaction (nested PCR) and its impact on patient survival.

Patients and methods:  One hundred and twenty‐four HSCT patients and 124 healthy volunteers were included in the study. Oral swabs were taken before, after 100 days and 1 year of HSCT at the buccal mucosa. Nested PCR was used to detect CMV in the saliva. Time of death after HSCT was displayed, by means of the Kaplan–Meier method, for the following parameters: age and gender of the patient, donor gender, primary disease, stem cell source, platelet number, chronic graft vs host disease (cGVHD) of salivary glands and oral mucosa, and oral CMV shedding. Cox proportional hazards model was used for multivariate survival analysis.

Results:  While none of the individuals in the control group showed positive swabs for CMV, the frequency of positive CMV oral swabs in patients at day + 100 after HSCT (45.2%) was statistically higher than before (7.2%) and 1 year after HSCT (17.5%). The presence of CMV was not associated with cGVHD and did not have any impact on post‐transplant survival.

Conclusions:  The present study shows that oral CMV shedding occurs after HSCT, especially at day +100 post‐transplant. Identification of CMV in the saliva might be important for the early diagnosis of CMV infection in allo‐HSTC.
TEXTURAL PROFILE ANALYSIS OF SUNFLOWER–SESAME KERNEL CONFECTION (CHIKKI)
Authors: GUPTA R.K. , SHARMA A. , SHARMA R.
Published: January 2007

Models capable of predicting textural quality of sunflower–sesame kernel confection (chikki) have been developed using response surface methodology. The model can be used to determine the effect of sunflower–sesame kernel proportions on texture profile analysis (TPA) parameters of the product. The quality attributes measured were hardness, cohesiveness, springiness, chewiness and resilience, whose values varied from 100–183 N, 1.01–2.82, 1.00–1.18, 21.7–495.1 N and 0.297–0.436, respectively. The highest values of hardness, chewiness and resilience were attained for the snacks prepared using jaggery (brown sugar) : sunflower kernel : sesame kernel in the ratio of 50:35:25. The highest values of cohesiveness and springiness were observed with 50:25:15 (jaggery : sunflower : sesame) proportions. The sensory term overall acceptability of the snacks is significantly correlated with instrumental cohesiveness, springiness and chewiness, which are the desired quality attributes of the snacks.

PRACTICAL APPLICATIONS

Popularizing sunflower kernel in the diet can help combat protein–calorie malnutrition in children to a certain extent in developing countries. This research may provide an opportunity to consider sunflower kernel as an ingredient in new products by manufacturers of baked goods and snack foods. The objective of the study was to quantify characteristics of textural profile of sunflower–sesame kernel chikki prepared using various proportions of sunflower and sesame kernels. Models developed using response surface methodology for predicting the textural quality of snacks can be used to determine the effect of sunflower–sesame kernel proportions on texture profile analysis parameters of the product. The confection (chikki) prepared taking jaggery, sunflower and sesame kernels as ingredients is an organoleptically accepted product.
Aboriginal and Torres Strait Islander Peoples and the Burden of Stroke
Authors: Thrift Amanda G. , Hayman Noel
Published: January 2007

Aboriginal and Torres Strait Islander peoples comprise about 2·4% of the Australian population. There is little information about stroke among these groups of people. Most information comes from national mortality and hospital morbidity data, and population-based surveys of risk factors. Hospitalisations for stroke among Aboriginal and Torres Strait Islander peoples are 1·2-fold that of non-Indigenous males and 1·9-fold that of non-Indigenous females. Similarly, deaths from stroke are greater among Indigenous Australians, being approximately double that of non-Indigenous Australians. The disparity in stroke deaths is greatest among younger individuals. Differences in hospitalisations and mortality from stroke can be attributed to both a greater prevalence of modifiable risk factors for stroke among the Indigenous population and poorer access to acute care services. Access to appropriate primary health care is also problematic for many Indigenous Australians, mainly because of their distance from health services and lack of available transport. Stroke and its risk factors are common among Aboriginal and Torres Strait Islander peoples. Adopting national and state strategy actions, such as providing a comprehensive primary health care program and increased training and support for health care providers, is urgently needed to reduce the incidence of stroke in these groups. However, continued efforts across the health care sector are required to ensure stroke reduction in Aboriginal and Torres Strait Islander peoples.
Pancreatic islet blood flow during euglycaemic, hyperinsulinaemic clamp in anaesthetized rats
Authors: Jansson L. , Andersson A. , Bodin B. , Källskog Ö.
Published: January 2007

Aims:  Previous studies have demonstrated that pancreatic islet blood flow is crucially dependent on blood glucose concentration. Thus, hyperglycaemia increases and hypoglycaemia decreases islet blood perfusion, by a combination of nervous and metabolic signals. The aim of the present study was to evaluate if hyperinsulinaemia, without associated hypoglycaemia, affects islet blood flow.

Methods:  Thiobutabarbital‐anaesthetized Wistar–Furth rats were subjected to an euglycaemic, hyperinsulinaemic clamp, that is they were infused for 60 min with either saline, insulin (18 mU kg−1 min−1), glucose (27 mg kg−1 min−1) or both glucose and insulin. This was followed by islet blood flow measurements with a microsphere technique.

Results:  Animals receiving only glucose doubled their blood glucose and serum insulin concentrations, whereas rats receiving only insulin had blood glucose concentrations <2 mmol L−1 and a 10‐fold increase in serum insulin concentrations. Animals given simultaneous glucose and insulin had normal blood glucose concentrations but a 10‐fold increase in serum insulin concentrations. Total pancreatic blood flow was unaffected in all animals. Islet blood flow was increased in hyperglycaemic and decreased in hypoglycaemic rats compared with control rats. Islet blood flow did not differ between clamped and control rats.

Conclusions:  Serum insulin concentration per se does not affect islet blood flow, whereas the ambient blood glucose concentration is of major importance in this context.
The “Disparate Impact” Argument Reconsidered: Making Room for Justice in the Assisted Suicide Debate
Authors: Coleman Carl H.
Published: January 2007

In “Should We Impose Quotas? Evaluating the ‘Disparate Impact’ Argument Against Legalization of Assisted Suicide,” Ronald Lindsay argues that it should make no difference to the debate over legalizing assisted suicide whether the risks associated with legalization would fall disproportionately on the poor, people with disabilities, racial minorities, or any other especially vulnerable social group. Even assuming such an inequitable distribution of risks would occur, he maintains, attempting to avoid such an outcome is not a good reason to deny assisted suicide to “competent persons who truly voluntarily choose it.”

Those of us who worry that legalization will differentially burden already disadvantaged segments of society have generally taken it for granted that the possibility of such disparities raises significant public policy concerns. By insisting on an explanation of this assumption — and, in so doing, making explicit the tension between autonomy and equality that underlies the assisted suicide debate — Lindsay has significantly advanced the ongoing conversation. While I disagree with his analysis, I commend him for a thoughtful, provocative, and important contribution to the literature.
Placebo Surgery for Parkinson's Disease: Do the Benefits Outweigh the Risks?
Authors: Clark Peter A.
Published: January 2007

In April 1999, Dr. Curt Freed of the University of Colorado in Denver and Dr. Stanley Fahn of Columbia Presbyterian Center in New York presented the results of a four-year, $5.7 million government-financed study using tissue from aborted fetuses to treat Parkinson’s disease at a conference of the American Academy of Neurology. The results of the first government-financed, placebo-controlled clinical study using fetal tissue showed that the symptoms of some Parkinson’s patients had been relieved. This research study involved forty subjects, nineteen women and twenty-one men; all suffered from Parkinson’s disease for an average of 13.5 years. In the study, each subject underwent neurosurgery: “four tiny burr holes, drilled through the wrinkle lines above the eyebrows into the skull, to clear a pathway to the brain. But only half received injections of fetal cells into the putamen, the region of the brain that controls movement; the other half received nothing. One year later, three members of the placebo group said their symptoms had improved.” In two-thirds of the transplant recipients, the fetal tissue took hold and seemed to establish a new network to produce the missing neurochemical dopamine.
Health-Care Rationing: Critical Features, Ordinary Language, and Meaning
Authors: Russell Barbara J.
Published: January 2007

The purpose of this article is to re-visit how rationing is defined for a health-care context, Two reasons justify returning to this topic. First, the variability as to how rationing has been defined in the legal, medical, and philosophical literature justifies a careful examination to identify its critical features. Second, I believe that if the definitions typically employed in the literature, several of which are discussed below, are compared to those that would be offered by the American public, ethically weighty dissimilarities would be apparent. Disparate characterizations are worrisome because serious “disconnections” between policymakers’ understandings, rhetoric, and priorities and those of the general public are more likely.
Computer Vision‐Based Sorting of Atlantic Salmon (Salmo salar) Fillets According to Their Color Level
Authors: Misimi E. , Mathiassen J.R. , Erikson U.
Published: January 2007

ABSTRACT: Computer vision method was used to evaluate the color of Atlantic salmon (Salmo salar) fillets. Computer vision‐based sorting of fillets according to their color was studied on 2 separate groups of salmon fillets. The images of fillets were captured using a digital camera of high resolution. Images of salmon fillets were then segmented in the regions of interest and analyzed in red, green, and blue (RGB) and CIE Lightness, redness, and yellowness (Lab) color spaces, and classified according to the Roche color card industrial standard. Comparisons of fillet color between visual evaluations were made by a panel of human inspectors, according to the RocheSalmoFan™ lineal standard, and the color scores generated from computer vision algorithm showed that there were no significant differences between the methods. Overall, computer vision can be used as a powerful tool to sort fillets by color in a fast and nondestructive manner. The low cost of implementing computer vision solutions creates the potential to replace manual labor in fish processing plants with automation.
Broad-Spectrum Anti-Human Immunodeficiency Virus (HIV) Potential of a Peptide HIV Type 1 Entry Inhibitor
Authors: Cocklin Simon , Gopi Hosahudya , Querido Bianca , Nimmagadda Manideepthi , Kuriakose Syna , Cicala Claudia , Ajith Sandya , Baxter Sabine , Arthos James , Martín-García Julio , Chaiken Irwin M.
Published: January 2007

The AIDS epidemic continues to spread at an alarming rate worldwide, especially in developing countries. One approach to solving this problem is the generation of anti-human immunodeficiency virus (HIV) compounds with inhibition spectra broad enough to include globally prevailing forms of the virus. We have examined the HIV type 1 (HIV-1) envelope specificity of a recently identified entry inhibitor candidate, HNG-105, using surface plasmon resonance spectroscopy and pseudovirus inhibition assays. The combined results suggest that the HNG-105 molecule may be effective across the HIV-1 subtypes, and they highlight its potential as a lead for developing therapeutic and microbicidal agents to help combat the spread of AIDS.
Association of Gamma Interferon and Interleukin-17 Production in Intestinal CD4+T Cells with Protection against Rotavirus Shedding in Mice Intranasally Immunized with VP6 and the Adjuvant LT(R192G)
Authors: Smiley Kristi L. , McNeal Monica M. , Basu Mitali , Choi Anthony H.-C. , Clements John D. , Ward Richard L.
Published: January 2007

Mucosal immunization of mice with chimeric,Escherichia coli-expressed VP6, the protein that comprises the intermediate capsid layer of the rotavirus particle, together with attenuatedE. coliheat-labile toxin LT(R192G) as an adjuvant, reduces fecal shedding of rotavirus antigen by >95% after murine rotavirus challenge, and the only lymphocytes required for protection are CD4+T cells. Because these cells produce cytokines with antiviral properties, the cytokines whose expression is upregulated in intestinal memory CD4+T cells immediately after rotavirus challenge of VP6/LT(R192G)-immunized mice may be directly or indirectly responsible for the rapid suppression of rotavirus shedding. This study was designed to identify which cytokines are significantly upregulated in intestinal effector sites and secondary lymphoid tissues of intranasally immunized BALB/c mice after challenge with murine rotavirus strain EDIM. Initially, this was done by using microarray analysis to quantify mRNAs for 96 murine common cytokines. With this procedure, the synthesis of mRNAs for gamma interferon (IFN-γ) and interleukin-17 (IL-17) was found to be temporarily upregulated in intestinal lymphoid cells of VP6/LT(R192G)-immunized mice at 12 h after rotavirus challenge. These cytokines were also produced in CD4+T cells obtained from intestinal sites specific to VP6/LT(R192G)-immunized mice after in vitro exposure to VP6 as determined by intracellular cytokine staining and secretion of cytokines. Although genetically modified mice that lack receptors for either IFN-γ or IL-17 remained protected after immunization, these results provide suggestive evidence that these cytokines may play direct or indirect roles in protection against rotavirus after mucosal immunization of mice with VP6/LT(R192G).
INTER-ORGANISATIONAL TIME: THE EXAMPLE OF QUEBEC BIOTECHNOLOGY
Authors: BONNEAU LINE
Published: January 2007

This paper introduces the notion of inter-organisational time, a dominant temporal institution at the organisational field level, and an environmental dimension absent from the extant literature. I argue that concepts such as temporal institutions and entrainment can help explain persistent dynamics in an organisational field that pace innovative activities. I use Quebec's biopharmaceutical field to illustrate a shift in inter-organisational time since the technology bubble burst. I suggest that including inter-organisational time in future analyses of organisational fields may improve understanding of the strategic context of innovation.
THE ROUTE TO LONG-TERM SUCCESS OF TECHNOLOGY COMPANIES
Authors: FLECK DENISE
Published: January 2007

Long-term success requires the challenging task of persistently creating and capturing value. Institutional theory addresses persistence in organisations and inter-organisational fields, but uncovers a paradox: while institutionalisation increases survival chances, it generates inertia, rigidity, and resistance to change, and therefore reduces long-term competitive advantage. The historical analysis of two long-lived electrical manufacturing companies (General Electric and Westinghouse) suggests that both developed a distinctive technological competence, and, for many decades, persistently created value. However, General Electric's distinctive competences also included dynamic and value-capture capabilities. These findings suggest that long-term success may occur in the presence of institutionalisation, if institutionalisation encompasses dynamic capabilities. In addition, this paper suggests that a resource-preservation dimension be included in the dynamic capabilities construct and in institutional theory, and that depending on how institutionalisation is conducted, the organisation may create habits that prevent or foster the side effects of institutionalisation processes.
The role of actin cytoskeleton in oscillatory fluid flow-induced signaling in MC3T3-E1 osteoblasts
Authors: Malone Amanda M. D. , Batra Nikhil N. , Shivaram Giri , Kwon Ron Y. , You Lidan , Kim Chi Hyun , Rodriguez Joshua , Jair Kai , Jacobs Christopher R.
Published: January 2007

Fluid flow due to loading in bone is a potent mechanical signal that may play an important role in bone adaptation to its mechanical environment. Previous in vitro studies of osteoblastic cells revealed that the upregulation of cyclooxygenase-2 (COX-2) and c-fos induced by steady fluid flow depends on a change in actin polymerization dynamics and the formation of actin stress fibers. Exposing cells to dynamic oscillatory fluid flow, the temporal flow pattern that results from normal physical activity, is also known to result in increased COX-2 expression and PGE2release. The purpose of this study was to determine whether dynamic fluid flow results in changes in actin dynamics similar to steady flow and to determine whether alterations in actin dynamics are required for PGE2release. We found that exposure to oscillatory fluid flow did not result in the development of F-actin stress fibers in MC3T3-E1 osteoblastic cells and that inhibition of actin polymerization with cytochalasin D did not inhibit intracellular calcium mobilization or PGE2release. In fact, PGE2release was increased threefold in the polymerization inhibited cells and this PGE2release was dependent on calcium release from the endoplasmic reticulum. This was in contrast to the PGE2release that occurs in normal cells, which is independent of calcium flux from endoplasmic reticulum stores. We suggest that this increased PGE2release involves a different molecular mechanism perhaps involving increased deformation due to the compromised cytoskeleton.
Multiplicative Computation in the Vestibulo-Ocular Reflex (VOR)
Authors: Zhou Wu , Xu Youguo , Simpson Ivra , Cai Yidao
Published: January 2007

Multiplicative computation is a basic operation that is crucial for neural information processing, but examples of multiplication by neural pathways that perform well-defined sensorimotor transformations are scarce. Here in behaving monkeys, we identified a multiplication of vestibular and eye position signals in the vestibulo-ocular reflex (VOR). Monkeys were trained to maintain fixation on visual targets at different horizontal locations and received brief unilateral acoustic clicks (1 ms, rarefaction, 85∼110 db NHL) that were delivered into one of their external ear canals. We found that both the click-evoked horizontal eye movement responses and the click-evoked neuronal responses of the abducens neurons exhibited linear dependencies on horizontal conjugate eye position, indicating that the interaction of vestibular and horizontal conjugate eye position was multiplicative. Latency analysis further indicated that the site of the multiplication was within the direct VOR pathways. Based on these results, we propose a novel neural mechanism that implements the VOR gain modulation by fixation distance and gaze eccentricity. In this mechanism, the vestibular signal from a single labyrinth interacts multiplicatively with the position signals of each eye (Principle of Multiplication). These effects, however, interact additively with the other labyrinth (Principle of Addition). Our analysis suggests that the new mechanism can implement the VOR gain modulation by fixation distance and gaze eccentricity within the direct VOR pathways.
Synaptic Activation of Dendritic AMPA and NMDA Receptors Generates Transient High-Frequency Firing in Substantia Nigra Dopamine Neurons In Vitro
Authors: Blythe Sarah N. , Atherton Jeremy F. , Bevan Mark D.
Published: January 2007

Transient high-frequency activity of substantia nigra dopamine neurons is critical for striatal synaptic plasticity and associative learning. However, the mechanisms underlying this mode of activity are poorly understood because, in contrast to other rapidly firing neurons, high-frequency activity is not evoked by somatic current injection. Previous studies have suggested that activation of dendritic N-methyl-d-aspartate (NMDA) receptors and/or G-protein-coupled receptor (GPCR)-mediated reduction of action potential afterhyperpolarization and/or activation of cation channels underlie high-frequency activity. To address their relative contribution, transient high-frequency activity was evoked using local electrical stimulation (1 s, 10–100 Hz) in brain slices prepared from p15–p25 rats in the presence of GABA and D2 dopamine receptor antagonists. The frequency, pattern, and morphology of action potentials evoked under these conditions were similar to those observed in vivo. Evoked activity and reductions in action potential afterhyperpolarization were diminished greatly by application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or NMDA receptor selective antagonists and abolished completely by co-application of AMPA and NMDA antagonists. In contrast, application of glutamatergic and cholinergic GPCR antagonists moderately enhanced evoked activity. Dendritic pressure-pulse application of glutamate evoked high-frequency activity that was similarly sensitive to antagonism of AMPA or NMDA receptors. Taken together, these data suggest that dendritic AMPA and NMDA receptor-mediated synaptic conductances are sufficient to generate transient high-frequency activity in substantia nigra dopamine neurons by rapidly but transiently overwhelming the conductances underlying action potential afterhyperpolarization and/or engaging postsynaptic voltage-dependent ion channels in a manner that overcomes the limiting effects of afterhyperpolarization.
Developmental Reorganization of the Output of a GABAergic Interneuronal Circuit
Authors: Xu Huaying , Clement Arthur , Wright Terrence Michael , Wenner Peter
Published: January 2007

Locally projecting inhibitory interneurons play a crucial role in the patterning and timing of network activity. However, because of their relative inaccessibility, little is known about their development or incorporation into circuits. In this report we demonstrate that the GABAergic R-interneuron circuit undergoes a reorganization in the chick embryo spinal cord between embryonic days 8 and 15 (E8 and E15). R-interneurons receive synaptic input from and project back to motoneurons. By stimulating motoneurons projecting in one ventral root and recording the disynaptic response from motoneurons in adjacent segments, we show that the output of the R-interneuron circuit is reorganized during development. After stimulation of the LS2 ventral root, disynaptic responses observed in whole cell recordings became more common and stronger for LS3 motoneurons and less common for the more distant LS4 motoneurons from E8 to E10. Optical studies demonstrated that R-interneurons activated by LS2 stimulation were restricted to the LS2 segment and had a small glutamatergic component at both E8 and E10, but that more R-interneurons were activated within the segment by E10. The recruitment of more LS2 R-interneurons at E10 is likely to contribute to stronger projections to LS3 motoneurons, but the fact that fewer LS4 motoneurons receive this input is more consistent with a functional refinement of the more distant projection of the GABAergic R-interneuron. Interestingly, this pattern of reorganization was not observed throughout the rostrocaudal extent of the cord, introducing the possibility that refinement could serve to remove connections between functionally unrelated interneurons and motoneurons.
BNIP3 as a Progression Marker in Primary Human Breast Cancer; Opposing Functions inIn situVersus Invasive Cancer
Authors: Tan Ern Yu , Campo Leticia , Han Cheng , Turley Helen , Pezzella Francesco , Gatter Kevin C. , Harris Adrian L. , Fox Stephen B.
Published: January 2007

Purpose: BNIP3 is involved in cell death and cell survival via autophagy. Its perinecrotic localization within ductal carcinoma in situ (DCIS) suggests an involvement in neoplastic cellular adaptation to low oxygen tension. This study has investigated the role of BNIP3 in normal and neoplastic breast.

Experimental Design: Whole sections from 11 normal breast and microarrayed tissue cores from 81 DCIS and 251 invasive carcinomas were stained for BNIP3 and hypoxia-inducible factor-1α. The pattern and level of BNIP3 expression were correlated with clinicopathologic variables and hypoxia-inducible factor-1α.

Results: BNIP3 expression was significantly up-regulated in the cytoplasm of DCIS and invasive carcinoma compared with normal breast (P = 0.0005 and P < 0.0001, respectively). Nuclear BNIP3 expression was associated with smaller tumor size (P = 0.04), low tumor grade (P = 0.005), and estrogen receptor positivity (P = 0.008) in invasive tumors. Nuclear BNIP3 expression was also associated with a longer disease-free survival among low-grade and estrogen receptor–positive tumors. (P = 0.03 and 0.04, respectively). Conversely, nuclear BNIP3 expression in DCIS was associated with a 3-fold increase in recurrence and a shorter disease-free survival (P = 0.03).

Conclusions: Up-regulation of BNIP3 expression in DCIS and invasive carcinoma suggests a significant role in breast tumor progression. Its association with good survival outcome in invasive carcinoma but with an increased risk of recurrence and shorter disease-free survival in DCIS may suggest a pivotal switch from a cell death to survival function during the transition from preinvasive to invasive breast cancer.
Phase 1b Dose Escalation Study of Erlotinib in Combination with Infusional 5-Fluorouracil, Leucovorin, and Oxaliplatin in Patients with Advanced Solid Tumors
Authors: Hanauske Axel-R. , Cassidy Jim , Sastre Javier , Bolling Claus , Jones Robert J. , Rakhit Ashok , Fettner Scott , Brennscheidt Ulrich , Feyereislova Andrea , Díaz-Rubio Eduardo
Published: January 2007

Purpose: Erlotinib (Tarceva) is a potent epidermal growth factor receptor (HER1) inhibitor. Infusional 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX) is a standard therapy for colorectal cancer. This trial assessed the maximum tolerated dose (MTD), safety, preliminary efficacy, and pharmacokinetics of erlotinib combined with FOLFOX.

Experimental Design: Patients with advanced solid tumors were sequentially enrolled into three cohorts (cohort 1: 100 mg/d erlotinib, 65 mg/m2 oxaliplatin, 200 mg/m2 leucovorin, 400 mg/m2 bolus 5-FU, and 400 mg/m2 continuous infusion 5-FU; cohort 2: oxaliplatin increased to 85 mg/m2 and 5-FU infusion increased to 600 mg/m2; and cohort 3: erlotinib increased to 150 mg/d).

Results: Thirty-two patients were enrolled (23 with colorectal cancer): no dose-limiting toxicities (DLT) were observed in cohort 1. In cohort 2, two of nine patients experienced a DLT (both diarrhea). In cohort 3, two of nine patients had a DLT (diarrhea and staphylococcal septicemia). Cohort 3 determined the MTD cohort and expanded to 17 patients in total. The most common adverse events were diarrhea, nausea, stomatitis, and rash (primarily mild/moderate). No pharmacokinetics interactions were observed. One patient (colorectal cancer) had a complete response, seven patients had a partial response, and nine had stable disease.

Conclusions: The MTD was defined as follows: 150 mg/d erlotinib, 85 mg/m2 oxaliplatin; 200 mg/m2 leucovorin, 400 mg/m2 bolus 5-FU, and 600 mg/m2 infusion 5-FU. At the MTD, the combination was well tolerated and showed antitumor activity, warranting further investigation in patients with advanced colorectal cancer and other solid tumors.
CD8+ T-Cell Content in Diagnostic Lymph Nodes Measured by Flow Cytometry Is a Predictor of Survival in Follicular Lymphoma
Authors: Wahlin Björn Engelbrekt , Sander Birgitta , Christensson Birger , Kimby Eva
Published: January 2007

Purpose: Follicular lymphoma is a heterogeneous disease with variable prognosis and clinical course. We hypothesized that the presence of nonmalignant T cells in the microenvironment of the tumor may affect the outcome.

Experimental Design: Using flow cytometry, we evaluated the T-cell subsets in the lymph node microenvironment of follicular lymphoma. All patients in South Stockholm County with indolent follicular lymphoma and with flow cytometry done on a diagnostic lymph node between 1994 and 2004 were included (N = 139). Diagnosis and grade (1, 2, and 3a) were confirmed by re-review. Flow cytometry results were reanalyzed. Lymphocyte subsets, the Follicular Lymphoma International Prognostic Index, grade, and clinical characteristics were evaluated in univariable and multivariable Cox analysis with respect to overall survival (OS) and disease-specific survival (DSS).

Results: Higher CD8+ T-cell levels correlated with longer OS and DSS, independently of the Follicular Lymphoma International Prognostic Index (OS, P = 0.017; DSS, P = 0.020) and independently of all other prognostic factors (OS, P = 0.001; DSS, P = 0.004). Median OS was not reached for patients in the upper quarter of CD8+ T-cell levels (>8.6%), 10.4 years for patients in the middle half (4.2-8.6%), and 6.0 years for patients in the lower quarter (<4.2%). Furthermore, patients who had not required treatment within 6 months from diagnosis had more CD8+ T cells (P = 0.011).

Conclusions: Higher levels of CD8+ T cells predict a better prognosis, and these data support an important role for nonmalignant immune cells in the biology of follicular lymphoma. Evaluating the CD8+ T cells by flow cytometry at diagnosis may provide prognostic information.
Protein Expression Profiling in High-Risk Breast Cancer Patients Treated with High-Dose or Conventional Dose–Dense Chemotherapy
Authors: Diallo-Danebrock Raihanatou , Ting Evelyn , Gluz Oleg , Herr Alexander , Mohrmann Svjetlana , Geddert Helene , Rody Achim , Schaefer Karl-Ludwig , Baldus Stephan E. , Hartmann Arndt , Wild Peter J. , Burson Michael , Gabbert Helmut E. , Nitz Ulrike , Poremba Christopher
Published: January 2007

Purpose: To characterize the prognostic and predictive impact of protein expression profiles in high-risk breast cancer patients who had previously been shown to benefit from high-dose chemotherapy (HDCT) in comparison to dose-dense chemotherapy (DDCT).

Experimental Design: The expression of 34 protein markers was evaluated using tissue microarrays containing paraffin-embedded breast cancer samples from 236 patients who were randomized to the West German Study Group AM01 trial.

Results: (a) 24 protein markers of the initial panel of 34 markers were sufficient to identify five profile clusters (subtypes) by K-means clustering: luminal-A (27%), luminal-B (12%), HER-2 (21%), basal-like (13%) cluster, and a so-called “multiple marker negative” (MMN) cluster (27%) characterized by the absence of specifying markers. (b) After DDCT, HER-2 and basal-like groups had significantly worse event-free survival [EFS; hazard ratio (HR), 3.6 [95% confidence interval (95% CI), 1.65-8.18; P = 0.001] and HR, 3.7 (95% CI, 1.68-8.48; P < 0.0001), respectively] when compared with both luminal groups. (c) After HDCT, the HR was 1.5 (95% CI, 0.76-3.05) for EFS in the HER-2 subgroup and 1.1 (95% CI, 0.37-3.32) in the basal-like subgroup, which indicates a better outcome for patients in the HER-2 and basal-like subgroups who received HDCT. The MMN cluster showed a trend to a better EFS after HDCT compared with DDCT.

Conclusions: Protein expression profiling in high-risk breast cancers identified five subtypes, which differed with respect to survival and response to chemotherapy: In contrast to luminal-A and luminal-B subtypes, HER-2 and basal-like subgroups had a significant predictive benefit, and the MMN cluster had a trend to a predictive benefit, both from HDCT when compared with DDCT.
Protein Expression Profiles in Renal Cell Carcinoma: Staging, Prognosis, and Patient Selection for Clinical Trials
Authors: Lam John S. , Pantuck Allan J. , Belldegrun Arie S. , Figlin Robert A.
Published: January 2007

Attempts to predict survival in patients with renal cell carcinoma (RCC) have traditionally relied on standard clinical variables, such as tumor-node-metastasis stage, histologic grade, and performance status. An accurate method for predicting patient survival is useful for patient counseling, planning follow-up, and selecting patients most likely to benefit from novel and established therapies. Furthermore, an improved prognostic system will allow for more accurate comparisons of clinical trials based on varying inclusion criteria. A large number of potential prognostic markers have recently been identified from methods based on gene arrays, which screen for differential expression of thousands of genes. The accepted method of clinical validation of novel markers is on formalin-fixed and paraffin-embedded specimens using immunohistochemistry. The development of tissue microarrays as a high-throughput technique has allowed for thousands of different cores of pathologic tissue to be assessed simultaneously in a timely and cost-efficient manner. This technology has enabled the analysis of protein expression profiles on specimens to determine their potential clinical significance and role in RCC biology. This article reviews the protein expression profiles in RCC and their association with pathobiology, prognosis, and response to treatment as well as their role in serving as potential molecular targets for therapy of RCC.
Genomics of Renal Cell Cancer: The Biology Behind and the Therapy Ahead
Authors: Jones Jon , Libermann Towia A.
Published: January 2007

Renal cell cancer (RCC) is the most lethal of the urological cancers and accounts for 3% of all adult malignancies. Despite numerous recent advances in diagnostic imaging, surgical therapy, and basic molecular understanding, many patients still experience metastatic disease. For metastatic disease patients, response rates to conventional therapies rarely exceed 15% to 25% and are associated with serious adverse effects. The recent development of novel targeted therapies based on the precise biological pathways deregulated in a particular patient has paved the way for individualized, targeted patient management. Nevertheless, to achieve this goal, it is important to delineate the molecular mechanisms underlying cancer development and progression. Genomic approaches have revolutionized the field of cancer research and have led to the rapid discovery of multiple, parallel disease hypotheses, which ultimately have to be validated in large cohorts of patients and in downstream biological experiments for translation into clinical applications. The variable course of RCC and, until recently, a paucity of therapeutic options in the event of metastasis have led to the search for diagnostic and prognostic markers. We and others have used transcriptional profiling to classify different subtypes of RCC and to identify subtype- and metastasis-specific gene signatures predictive for outcome. We discuss herein recent genomic approaches to RCC and the emerging biological pathways underlying RCC development and progression. We also speculate how genomics may affect drug development and the management of patients with RCC.
Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma: Is It Still Imperative in the Era of Targeted Therapy?
Authors: Pantuck Allan J. , Belldegrun Arie S. , Figlin Robert A.
Published: January 2007

In the era before cytokine therapy, controversy existed about the need for cytoreductive nephrectomy in treating patients with metastatic renal cell carcinoma. In 1978, Dekernion showed that nephrectomy alone had no effect on survival. During this period, removal of the malignant kidney was confined to palliative therapy in some settings of metastatic RCC, such as pain related to the kidney mass, intractable hematuria, erythrocytosis, uncontrolled hypertension, or poorly controlled hypercalcemia. When interleukin-2 was approved by the Food and Drug Administration in 1992, the role of nephrectomy was reexamined. After a decade of controversy, two randomized controlled studies established that cytoreductive surgery has a role in properly selected patients and offers a survival advantage when done before cytokine therapy. Unfortunately, the mechanisms underlying this benefit remain poorly understood. Immunotherapy may work best when there is a small volume of cancer present, and removing a large primary tumor may prevent the seeding of additional metastases. Data have also suggested that primary tumors were capable of producing immunosuppressive compounds that might decrease the efficacy of immunotherapy. Another hypothesis suggested that removing the kidney altered the acid/base status of the patient to such an extent that the growth of the tumor was hindered. With the emergence in 2006 of two targeted agents for advanced renal cell carcinoma, the role of cytoreductive nephrectomy has reemerged as a source of controversy. Although evidence-based medical practice suggests a role for nephrectomy before the use of targeted agents, the arguments for and against this practice will be weighed.
Investigating Indoor Air Quality and Thermal Comfort Using a Numerical Thermal Manikin
Authors: Gao N. P. , Zhang H. , Niu J. L.
Published: January 2007

In this paper, we investigated the pollutant exposure reduction and thermal comfort that can be achieved with personalised ventilation (PV) design when a PV system is combined with two types of background air conditioning systems. For the investigation of inhaled air quality, pollutants emitted from building materials are the targeted pollutants; and for the investigation of thermal comfort, local discomfort associated with nonuniform thermal environment is focused upon. These investigations were performed by combining CFD simulation of the 3D air flow and a multi-nodal humanbody thermo-regulation model. The results reveal some new characteristics of the three typical air distribution designs, i.e. mixed ventilation, displacement ventilation and PV, and provide insight into the possible optimisation of system combinations.
Comparison of Andersen and Honey Jar Methods for Monitoring Hospital Wards
Authors: Rodrigues Acacio Gonçalves , Araujo Ricardo
Published: January 2007

The objective of this study was to compare the “honey jar” (HJ) sedimentation method with the reference Andersen collection method and validate this new proposed technique for performing environmental monitoring of Aspergillus in health care and other working facilities. Sterile plastic jars were left open in an operating room and adjacent rooms and replaced at weekly intervals; control jars were placed in different hospital wards. Comparison of the HJ method with the Andersen impactor sampling method showed an agreement of 70%. Interestingly, the HJ technique yielded some positive results that were not detected by the Andersen sampling method, possibly due to its continuous monitoring. A significant difference regarding the isolation of Aspergillus species in an operating theatre was found by the HJ method between the first and the second and third study phases, which correlated with the changing of air filters and refurbishment of the air conditioning system. The HJ sedimentation technique represents a valid and low cost procedure for performing environmental studies involving airborne fungi. Our results also stress the importance and need for continuous monitoring of airborne Aspergillus in critical medical environments, particularly regarding important pathogens like Aspergillus fumigatus.
Comparison of different delivery systems of DNA vaccination for the induction of protection against tuberculosis in mice and guinea pigs
Authors: de Paula Lúcia , Silva Célio L , Carlos Daniela , Matias-Peres Camila , Sorgi Carlos A , Soares Edson G , Souza Patrícia RM , Bladés Carlos RZ , Galleti Fábio CS , Bonato Vânia LD , Gonçalves Eduardo DC , Silva Érika VG , Faccioli Lúcia H
Published: January 2007

The great challenges for researchers working in the field of vaccinology are optimizing DNA vaccines for use in humans or large animals and creating effective single-dose vaccines using appropriated controlled delivery systems. Plasmid DNA encoding the heat-shock protein 65 (hsp65) (DNAhsp65) has been shown to induce protective and therapeutic immune responses in a murine model of tuberculosis (TB). Despite the success of naked DNAhsp65-based vaccine to protect mice against TB, it requires multiple doses of high amounts of DNA for effective immunization. In order to optimize this DNA vaccine and simplify the vaccination schedule, we coencapsulated DNAhsp65 and the adjuvant trehalose dimycolate (TDM) into biodegradable poly (DL-lactide-co-glycolide) (PLGA) microspheres for a single dose administration. Moreover, a single-shot prime-boost vaccine formulation based on a mixture of two different PLGA microspheres, presenting faster and slower release of, respectively, DNAhsp65 and the recombinant hsp65 protein was also developed. These formulations were tested in mice as well as in guinea pigs by comparison with the efficacy and toxicity induced by the naked DNA preparation or BCG. The single-shot prime-boost formulation clearly presented good efficacy and diminished lung pathology in both mice and guinea pigs.
Cytologic findings in malignant myoepithelioma: a case report and review of the literature
Authors: Sauer Torill
Published: January 2007

Background

Myoepithelioma of the breast is a rare tumor and the cytologic features have only been described in one previous report.

Case presentation

The present case comprises a 70 year old woman with a mammographic equivocal and ultrasonographic suspicious lesion. The aspirates were cellular and consisted mainly of single spindle or polymorphic, polygonal cells. The nuclei were generally large, ranging from 2 - > 5 × RBC. Most nuclei had a distinct medium-sized nucleolus. The nuclear outlines were irregular with buds and folds. The chromatin was granular. In the background there was abundant granular metachromatic ground substance and some metachromatic stromal fragments. A few mitotic figures were found. The cytologic diagnosis was suspicious for malignancy and a metaplastic carcinoma where only the non-epithelial component had been aspirated, or a non-epithelial lesion, was suggested.

Macroscopically the tumor was round, seemingly well circumscribed, firm and with a white cut surface. The lesion consisted of spindled and polygonal cells with distinct pleomorphism. There were 6–9 mitoses per high power field (HPF). The tumor infiltrated in the surrounding fatty tissue. On immunohistochemistry, tumor cells were positive for smooth muscle actin, keratin MNF 116 and vimentin. Desmin and S-100 were negative.

Ultrastructurally, there were abundant tonofilaments, including globular filamentous bodies and granulated endocytoplasmic reticulum with many dilated cisterns. The histologic diagnosis was malignant myoepithelioma.

Conclusion

The case mirrors completely the WHO definition and the previous cytological and histological descriptions of malignant myoepitheliomas in the literature which describe a spindle cell population with unequivocal nuclear atypia, metachromatic background substance and mitoses.
Young Novice Driver Subtypes: Relationship to High-Risk Behavior, Traffic Accident Record, and Simulator Driving Performance
Authors: Deery Hamish A. , Fildes Brian N.
Published: January 2007

Two studies were undertaken to obtain empirical support for the existence of driver subtypes in the young novice driver population. In Study 1, 198 participants (55% male) aged 16 to 19 completed an extensive self-report questionnaire. Five novice driver subtypes were identified through a cluster analysis of personality and driving-related measures. Two relatively high-risk or deviant subtypes (Clusters 1 and 5) were identified, characterized by high levels of driving-related aggression, competitive speed, driving to reduce tension, sensation seeking, assaultiveness, and hostility. The individuals in Cluster 5 also reported low levels of emotional adjustment and high levels of depression, resentfulness, and irritability. In Study 2, a subset of participants from each of the subtypes drove several scenarios in a driving simulator. The subtypes differed in their responses to an emergency situation and several potential traffic hazards. They also differed in the proficiency with which they could control their attention among concurrent tasks in high workload situations. Most of the significant differences were related to lower levels of driving skill among the two most deviant subtypes (Clusters 1 and 5). The potential applications of this research include the design of training programs and other countermeasures to address the young novice driver crash problem.
Duration of Hospitalization and Post Discharge Suicide
Authors: Ho Ting‐Pong
Published: January 2007

A retrospective cohort of discharged patients from all public psychiatric hospitals in Hong Kong (1997–1999) was linked to suicide data from Coroner's court. Patients hospitalized shorter than 15 days had significantly lower suicide rates than longer stay patients. The results were fairly consistent across immediate/late post discharge periods, gender, age, diagnoses, and narrow/wide definitions of suicide. This finding was opposite of what has been reported in the literature. Short hospitalization carried different suicide risks in different service settings.