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Effect of heterogeneous structure in mechanically unstressed biofilms on overall growth.

In contrast to their name, biofilms are not always flat and homogeneous but instead often exhibit complex structural heterogeneity. It has been suggested that nonhomogeneous geometry is selected in order to increase biofilm growth rate. A previous study (Dockery and Klapper (2002) SIAM J. Appl. Math., 62, 853-869) of a model biofilm system in a static bulk fluid demonstrated that under some circumstances a flat biofilm-bulk fluid interface is linearly unstable to perturbation due to growth induced forces. Computations indicated that subsequent nonlinear evolution results in fingers and mushrooms of biofilm similar to structures observed in actual biofilms. However, the important complementary issue of biological functionality was not considered. Here a weakly nonlinear analysis of the simple growing biofilm layer model in Dockery and Klapper (2002, SIAM J. Appl. Math., 62, 853-869) is presented. It is argued that, at least in the case of biofilms free of external mechanical stress, overall growth is in fact generally inhibited by the presence of growing perturbations in the linear stage. Hence a more complex explanation of function is necessary.

Biofilms↗

Down-regulation of KAI1/CD82 protein expression in oral cancer correlates with reduced disease free survival and overall patient survival.

Oral Squamous Cell Carcinoma (OSCC) is a common malignancy. Treatment failure is mainly due to loco-regional disease recurrence. KAI1 is a newly discovered metastasis suppressor gene. Fifty-seven patients with primary OSCC underwent surgery alone or surgery and adjuvant radiotherapy. Immunohistochemical evaluation of KAI1/CD82 and p53 proteins was carried out on specimen obtained at surgery. Within neoplastic fields, KAI1/CD82 expression was downregulated and negative in 42/57 (73.7%) cases. p53 expression was positive in 26/57 (45.6%) cases. No correlation was noted between KAI1/CD82 and p53 expression or clinicopathological parameters. Univariate and multivariate Cox proportional hazard models showed a correlation between KAI1/CD82 expression with disease free survival (P = 0.01, P = 0.009) and overall survival (P = 0.04, P = 0.053) respectively.

Aged↗

Systematic analysis and overall toxicity evaluation of dioxins and hexachlorobenzene in human milk.

A systematic method for analyzing dioxins (PCDDs, PCDFs and dioxin-like PCBs), hexachlorobenzene (HCB), heptachlor epoxide and beta-hexachlorocyclohexane (HCH) in human milk was developed to determine the residual amount of HCB in human milk and to evaluate the overall toxicity of both dioxins and HCB in human milk. The fractionation behavior of HCB on chromatography with silica gel, alumina, and activated carbon/silica gel, and the concentrated sulfuric acid decomposition method, which is widely used as a dioxin cleanup method, were studied in order to make the preprocessing operation for HCB measurement compatible with that for conventional dioxin measurement. HCB was found to be eluted in the 2% dichloromethane (DCM)/hexane 60 ml fraction from an alumina column. Heptachlor epoxide and a part of beta-HCH were eluted in the 10% DCM/hexane 50 ml fraction from a silica gel column, while the remaining beta-HCH was eluted in the 25% DCM/hexane 60 ml fraction from an activated carbon/silica gel column. Moreover, HCB showed significant correlation with dioxin congeners having high toxicity equivalence factors (TEFs). The results suggest that the exposure route to HCB and its accumulation behavior in the human body are similar to those of the dioxins.

Chemistry Techniques, Analytical↗

Overall alcohol intake, beer, wine, and systemic markers of inflammation in western Europe: results from three MONICA samples (Augsburg, Glasgow, Lille).

AIM: Anti-inflammatory effects of moderate alcohol consumption have been proposed to explain why moderate alcohol intake lowers coronary heart disease risk. We investigated the relationship between overall alcohol, beer or wine consumption and markers of systemic inflammation in three different geographical areas in Europe. METHODS AND RESULTS: Cross-sectional samples, each representative of the general population from Germany, Scotland, and France (MONICA Augsburg 1994/95, 2275 men and 2186 women, 25-74 years; Glasgow MONICA 1994/95, 561/616, 25-74 years, and MONICA Lille 1994/95, 581/574, 35-64 years) were studied. Alcohol intake was assessed by standardized interview. Adjusted means of C-reactive protein (CRP), fibrinogen, white blood cell (WBC) count, plasma viscosity (PV), and albumin were calculated among categories of alcohol intake, and separately for beer or wine consumption, by multiple linear regression. Self-reported moderate daily alcohol intake up to 40 g was associated with lower concentrations of CRP, fibrinogen, PV and WBC count, compared to non-drinking and heavy drinking, even after adjustment for various potential confounders. CONCLUSIONS: Moderate consumption of either wine or beer is associated with lower levels of systemic inflammatory markers in three different European areas, suggesting that ethanol itself might be largely responsible for the potential anti-inflammatory effects of these beverages.

Adult↗

To predict progression-free survival and overall survival in metastatic renal cancer treated with sorafenib: pilot study using dynamic contrast-enhanced Doppler ultrasound.

INTRODUCTION: The objective of this study was to evaluate dynamic contrast-enhanced Doppler ultrasound (DCE-US) with perfusion software (Vascular Recognition Imaging) and contrast agent injection as a predictor of tumour response, progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: Thirty patients with a metastatic renal cell carcinoma (RCC) already enrolled in a double-blind randomised study were evaluated. Examinations were performed at baseline, and after 3 and 6 weeks on sorafenib or a placebo in patients with tumour targets that were accessible to DCE-US. RESULTS: A total of 85 examinations were performed, 30 at baseline, 28 at 3 weeks and 27 at 6 weeks. The combination of a decrease in contrast uptake exceeding 10% and stability or a decrease in tumour volume allowed us to discriminate seven good responders and 20 poor responders at 3 weeks. There was a statistically significant difference in PFS (p=10(-4)) and OS (p=10(-4)) between good and poor responders. CONCLUSION: DCE-US is a new noninvasive imaging technique which might be an effective tool for evaluating antiangiogenic drugs in renal cancer.

Adult↗

Spatial and temporal variability of the overall error of National Atmospheric Deposition Program measurements determined by the USGS collocated-sampler program, water years 1989-2001.

Data from the U.S. Geological Survey (USGS) collocated-sampler program for the National Atmospheric Deposition Program/National Trends Network (NADP/NTN) are used to estimate the overall error of NADP/NTN measurements. Absolute errors are estimated by comparison of paired measurements from collocated instruments. Spatial and temporal differences in absolute error were identified and are consistent with longitudinal distributions of NADP/NTN measurements and spatial differences in precipitation characteristics. The magnitude of error for calcium, magnesium, ammonium, nitrate, and sulfate concentrations, specific conductance, and sample volume is of minor environmental significance to data users. Data collected after a 1994 sample-handling protocol change are prone to less absolute error than data collected prior to 1994. Absolute errors are smaller during non-winter months than during winter months for selected constituents at sites where frozen precipitation is common. Minimum resolvable differences are estimated for different regions of the USA to aid spatial and temporal watershed analyses.

Air Pollutants↗

Clinical characteristics and overall survival in genitourinary sarcomas treated with curative intent: a multicenter study.

OBJECTIVES: Adult soft tissue sarcomas in general, and those arising from the urological organs in particular, are a group of rare tumours with a generally poor prognosis, only a few studies are available. We report our experience with this type of tumours in a multicenter study carried out in a single region of Central Italy (Tuscany). METHODS: Pre-treatment and follow-up data were obtained from 22 adult patients, all residing in Tuscany, treated consecutively between 1984 and 2002 for primary or locally recurrent genito-urinary sarcomas in 8 urology departments in the area. All cases were classified according to the French Federation of Cancer Center System Grading Scheme for Adult Sarcomas (FFCC) and Broders System. The crude survival probability was estimated by using the Kaplan-Meier method and differences between patient sub-groups were assessed by the log rank test. RESULTS: The study series included 18 males and 4 females. The mean age at diagnosis was 61+/-21.5 years (range: 15.3-89.1). The most common site was paratesticular (n=9, 40.9%), followed by kidney (n=8, 36.4%), prostate (n=3, 13.6%) and penis and bladder (1 case each, 4.6%). 15 cases (68.2%) were classified as FFCC III, and 16 (72.7%) as Broders IV. The most common histological type was leiomyosarcoma (8 cases, 36.7%), followed by liposarcoma (6, 27.3%), rhabdomyosarcoma (3, 13.6%) and other histological types (5, 22.7%). At the last follow-up (mean: 3.66+/-3.25 years; range 0.15-10.0), 11 of the 22 patients (50%) were still alive. The overall survival rate at 1, 3 and 5 years was 85.9%, 62.0% and 48.8%, respectively. There were no significant differences in survival according to sex, age or histological type. When we compared paratesticular vs. kidney and prostate cancer cases, a significant difference in survival emerged (p=0.02). According to size and grade of the tumour we also found a significant difference in survival (p=0.0006 and p=0.01, respectively). CONCLUSIONS: In our representative series, 3 tumor parameters (site, size and grade) appeared to represent the most important prognostic factors in adult genitourinary sarcomas.

Adult↗

The homozygous M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase results in reduced enzyme activities but not in altered overall cellular sialylation in hereditary inclusion body myopathy.

Hereditary inclusion body myopathy (HIBM) is a neuromuscular disorder, caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, the key enzyme of sialic acid biosynthesis. In Middle Eastern patients a single homozygous mutation occurs, converting methionine-712 to threonine. Recombinant expression of the mutated enzyme revealed slightly reduced N-acetylmannosamine kinase activity, in agreement with the localization of the mutation within the kinase domain. B lymphoblastoid cell lines derived from patients expressing the mutated enzyme also display reduced UDP-N-acetylglucosamine 2-epimerase activity. Nevertheless, no reduced cellular sialylation was found in those cells by colorimetric assays and lectin analysis, indicating that HIBM is not directly caused by an altered overall expression of sialic acids.

Amino Acid Substitution↗

Elective cryopreservation of embryos at the pronucleate stage in women at risk of ovarian hyperstimulation syndrome may affect the overall pregnancy rate.

The aim of this retrospective study was to assess the pregnancy outcome and incidence of severe ovarian hyperstimulation syndrome (OHSS) in patients at risk of developing OHSS who had embryo cryopreservation at pronucleate stage and deferred embryo transfer in a university-affiliated teaching hospital over a 5-year period. Elective embryo cryopreservation and deferred transfer in patients at risk of OHSS does not compromise the cumulative pregnancy rate per patient and also results in a low overall incidence of severe OHSS.

Cryopreservation↗

Ventricular assist devices and aggressive immunosuppression: looking beyond overall survival.

BACKGROUND: Patients bridged to heart transplantation with a ventricular assist device (VAD) developed coronary vasculopathy at the same rate as non-bridged patients despite having higher levels of pre-formed antibodies. We hypothesized that allosensitized VAD patients have higher levels of immunosuppression and thus different morbidity and causes of mortality. METHODS: Patients who received a transplant between January 1996 and May 2002 were separated into 2 groups based on the need for VAD support as a bridge to transplantation. Transplant and Inpatient Pharmacy Databases and charts were queried for date of transplantation, degree of allosensitization, use of desensitization therapy, immunosuppressive strategies, number of treated rejection episodes, and specific causes of death. RESULTS: This study investigated 238 patients (125 VAD patients, 113 non-VAD patients). VAD patients were more likely to be allosensitized than non-VAD patients (20% vs 5%, p < 0.01). OKT3 was given to 22% of VAD patients as anti-rejection prophylaxis and 14% received pre-transplant plasmapheresis. Non-VAD patients rarely were desensitized (2.6% of non-VAD patients). After transplantation, 68 VAD patients (54%) and 44 non-VAD patients (39%) had episodes of severe rejection requiring therapy. Episodes of rejection in VAD patients were commonly treated with steroids (90%), plasmapheresis (10%), and OKT3 (7%), and episodes of rejection in non-VAD patients were treated with steroids (76%) and OKT3 (8%). The 5-year survival for both groups was similar (90% and 86% respectively, p = 0.31). VAD patients commonly died of sepsis (75%), and non-VAD patients died of rejection (39%) and ischemic transplant cardiomyopathy (30%). CONCLUSION: When short-term outcomes between bridged and non-bridged heart transplant recipients were compared, overall survival was similar but causes of death differed. Findings in this study might aid in the post-operative management of patients bridged to transplantation with a VAD.

Aged↗

Validation of an overall model describing the effect of three environmental factors on the apparent D-value of Bacillus cereus spores.

Several factorial models extending the famous Bigelow model to describe the influence of the heating and recovery pH and a(w) conditions on bacterial heat resistance have been developed. These models can be associated in an overall multifactorial model describing the influences of heating and recovery conditions on D values. For Bacillus cereus strain ADQP 407 the model parameters characterising the environmental factor influences (pH, Temperature, a(w)) were evaluated. Determination of bacterial heat resistance in cream chocolate have been realised to validate these parameter values and to evaluate the level of the influence of food texture or different compounds not taken account of in the model.

Bacillus cereus↗

In-line monitoring of partial and overall solid concentration during solvent-mediated phase transition using Raman spectroscopy.

A calibration strategy for the continuous monitoring of solvent-mediated phase transition was developed using in situ Raman spectroscopy. Citric acid which exhibits enantiotropy during its anhydrous/monohydrate phase transition was selected as a model organic product. Using 25 samples in suspension, specific calibration of the spectral data was obtained for estimating in-line both the overall solid concentration in suspension and the composition of the solid phase. In addition to such key-measurements, reliable estimates of supersaturation were computed in-line from the mass balance of the solute. In order to validate the technique, anhydrous to monohydrate phase transition experiments were performed in suspensions at 15 degrees C and the kinetic process involved was monitored. Despite the use of various solid concentrations and reactor configurations, both the reproducibility and the reliability of the in situ Raman measurements are shown to be satisfactory.

Calibration↗

Investigation of relationship between change in locoregional control and change in overall survival in randomized controlled trials of modified radiotherapy in head-and-neck cancer.

PURPOSE: To establish whether a relationship exists between improvement in locoregional control (LRC) and improvement in overall survival (OS) in trials of modified radiotherapy for head-and-neck cancer and to attempt to quantify the relationship. METHODS AND MATERIALS: A systematic review of the literature was performed for randomized controlled trials of radiotherapy for head-and-neck cancer involving the use of altered fractionation or hypoxic sensitizers. The changes in LRC at 2 years and OS at 5 years were recorded for each trial. Regression analysis was used to investigate the relationship between the two variables. RESULTS: Nineteen relevant trials were identified. Fourteen reported sufficient data for analysis. Linear regression analysis showed a statistically significant correlation between LRC and OS with a slope of 0.67 (95% confidence interval, 0.38-0.96, p = 0.00017). CONCLUSIONS: We have demonstrated a relationship between a change in LRC and a change in OS in randomized trials of modified radiotherapy for head-and-neck cancer. A 10% improvement in the 2-year LRC is predicted to lead to a 6.7% improvement in the 5-year OS. This type of analysis may have applications in other tumor sites.

Dose Fractionation, Radiation↗

High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer: long-term results of a radiation dose escalation study.

PURPOSE: To determine whether high-dose radiation leads to improved outcomes in patients with non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: This analysis included 106 patients with newly diagnosed or recurrent Stages I-III NSCLC, treated with 63-103 Gy in 2.1-Gy fractions, using three-dimensional conformal radiation therapy (3D-CRT) per a dose escalation trial. Targets included the primary tumor and any lymph nodes > or =1 cm, without intentionally including negative nodal regions. Nineteen percent of patients (20/106) received neoadjuvant chemotherapy. Patient, tumor, and treatment factors were evaluated for association with outcomes. Estimated median follow-up was 8.5 years. RESULTS: Median survival was 19 months, and 5-year overall survival (OS) was 13%. Multivariate analysis revealed weight loss (p = 0.011) and radiation dose (p = 0.0006) were significant predictors for OS. The 5-year OS was 4%, 22%, and 28% for patients receiving 63-69, 74-84, and 92-103 Gy, respectively. Although presence of nodal disease was negatively associated with locoregional control under univariate analysis, radiation dose was the only significant predictor when multiple variables were included (p = 0.015). The 5-year control rate was 12%, 35%, and 49% for 63-69, 74-84, and 92-103 Gy, respectively. CONCLUSIONS: Higher dose radiation is associated with improved outcomes in patients with NSCLC treated in the range of 63-103 Gy.

Adult↗

Preoperative radiation with concurrent chemotherapy for resectable rectal cancer: effect of dose escalation on pathologic complete response, local recurrence-free survival, disease-free survival, and overall survival.

PURPOSE: Three Phase II studies of preoperative radiotherapy and concurrent 5FU chemotherapy were undertaken. The primary endpoints were acute toxicity and pathologic complete response rate (pCR). Secondary endpoints were local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). METHODS AND MATERIALS: A total of 134 patients with adenocarcinoma of the rectum (clinical T3/T4 or N1/N2) were treated. The initial cohort received 40 Gy in 20 fractions, the second 46 Gy in 23 fractions, and the third 50 Gy in 25 fractions. 5FU (225 mg/m2/day) was given continuously throughout radiotherapy. A total of 121 patients underwent surgical resection. RESULTS: Treatment was well tolerated. Grade 3/4 acute toxicity was observed in 13%, 4%, and 14% of patients in the 40 Gy, 46 Gy, and 50 Gy cohorts, respectively (p = 0.20). pCR was documented in 15%, 23%, and 33% of patients, respectively (p = 0.07). The 2-year actuarial LRFS was 72%, 90%, and 89% (p = 0.02); DFS was 62%, 84%, and 78% (p = 0.02); and OS was 72%, 94%, and 92%, respectively (p = 0.03). CONCLUSIONS: All treatment schedules were well tolerated. There was a trend toward increased pCR with higher doses. A statistically significant increase in LRFS, DFS, and OS was seen with radiation doses of 46 Gy and greater, but there was no difference between 46 Gy and 50 Gy.

Antimetabolites, Antineoplastic↗

Scoring of anatomic injury after trauma: AIS 98 versus AIS 90--do the changes affect overall severity assessment?

BACKGROUND: Although several changes were implemented in the 1998 update of the abbreviated injury scale (AIS 98) versus the previous AIS 90, both are still used worldwide for coding of anatomic injury in trauma. This could possibly invalidate comparisons between systems using different AIS versions. Our aim was to evaluate whether the use of different coding dictionaries affected estimation of Injury Severity Score (ISS), New Injury Severity Score (NISS) and probability of survival (Ps) according to TRISS in a hospital-based trauma registry. MATERIALS AND METHODS: In a prospective study including 1654 patients from Ulleval University Hospital, a Norwegian trauma referral centre, patients were coded according to both AIS 98 and AIS 90. Agreement between the classifications of ISS, NISS and Ps according to TRISS methodology was estimated using intraclass correlation coefficients (ICC) with 95% CI. RESULTS: ISS changed for 378 of 1654 patients analysed (22.9%). One hundred and forty seven (8.9%) were coded differently due to different injury descriptions and 369 patients (22.3%) had a change in ISS value in one or more regions due to the different scoring algorithm for skin injuries introduced in AIS 98. This gave a minimal change in mean ISS (14.74 versus 14.54). An ICC value of 0.997 (95% CI 0.9968-0.9974) for ISS indicates excellent agreement between the scoring systems. There were no significant changes in NISS and Ps. CONCLUSIONS: There was excellent agreement for the overall population between ISS, NISS and Ps values obtained using AIS 90 and AIS 98 for injury coding. Injury descriptions for hypothermia were re-introduced in the recently published AIS 2005. We support this change as coding differences due to hypothermia were encountered in 4.3% of patients in the present study.

Abbreviated Injury Scale↗

Overall Assessment of the Speaker's Experience of Stuttering (OASES): documenting multiple outcomes in stuttering treatment.

UNLABELLED: This paper describes a new instrument for evaluating the experience of the stuttering disorder from the perspective of individuals who stutter. Based on the World Health Organization's International Classification of Functioning, Disability, and Health [World Health Organization (2001). The International Classification of Functioning, Disability, & Health. Geneva: World Health Organization], the Overall Assessment of the Speaker's Experience of Stuttering (OASES) collects information about the totality of the stuttering disorder, including: (a) general perspectives about stuttering, (b) affective, behavioral, and cognitive reactions to stuttering, (c) functional communication difficulties, and (d) impact of stuttering on the speaker's quality of life. This paper summarizes scale development, reliability and validity assessment, and scoring procedures so clinicians and researchers can use the OASES to add to the available evidence about the outcomes of a variety of treatment approaches for adults who stutter. EDUCATIONAL OBJECTIVES: As a result of this activity, participants will be able to: (1) identify key issues related to the documentation of treatment outcomes in stuttering; (2) discuss the components of the international classification of functioning, disability, and health as they relate to the documentation of stuttering treatment outcomes; (3) evaluate and use a new measurement instrument for assessing the outcomes of stuttering treatment from the perspective of the person who stutters.

Adult↗

The two-step mode of growth in the scleractinian coral skeletons from the micrometre to the overall scale.

It has been known since the 19th century that coral skeletons are built of aragonite crystals with taxonomy-linked arrangements, but the way by which each coral species controls this crystallization process remains an unsolved question. The problem became still more intriguing when it was shown that isotopic compositions of coral aragonite were subject to taxonomy-linked influences (the "vital effect"). On the other hand, presence of an organic component in coral skeletons is also long known, but localization of these compounds is admittedly restricted to particular structures called "centres of calcifications." Fibres, the largely predominant part of the coral skeletons, are usually considered as purely mineral units. In this paper, it is shown that in both "centres of calcification" and fibres, organic compounds are associated with the mineral material at a deep structural level. A series of variously scaled observations and localized measurements allow recognition of the presence of an organic component at the nanometre scale. Far from being a freely operating process, crystallization of coral fibres is thus permanently controlled by the polyp basal ectoderm through a cyclic two-step process acting at the micrometre-scale. The biomineralization cycle begins by secretion of a proteoglycan matrix. As the composition of these sugars-proteins assemblages has been shown taxonomy dependent, the hypothesis can be made that multiple and long recognized specificities of coral skeletons are linked to this biochemically driven crystallization process. Additionally, this new concept of the biomineralization process in coral skeletons provides us with an access to the long term evolution of the Scleractinia. Remarkably, results of a skeleton-based approach using microstructural criteria (i.e., the spatial relationships of "centres of calcification" and the three-dimensional arrangements of fibres), are consistent with a molecular phylogenetic analysis carried out on the same species. Clearly, at the overall ontogenic level, the two-step growth mode of coral skeletons is also a valuable tool to reconstruct the evolutionary history of Scleractinia.

Acridine Orange↗