ANOVA P-value Research Articles

Proteome analysis of Acetobacter pasteurianus during acetic acid fermentation

Acetic acid bacteria (AAB) are Gram-negative, strictly aerobic microorganisms that show a unique resistance to ethanol (EtOH) and acetic acid (AcH). Members of the Acetobacter and Gluconacetobacter genera are capable of transforming EtOH into AcH via the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) enzymes and are used for the industrial production of vinegar. Several mechanisms have been proposed to explain how AAB resist high concentrations of AcH, such as the assimilation of acetate through the tricarboxylic acid (TCA) cycle, the export of acetate by various transporters and modifications of the outer membrane. However, except for a few acetate-specific proteins, little is known about the global proteome responses to AcH. In this study, we used 2D-DIGE to compare the proteome of Acetobacter pasteurianus LMG 1262(T) when growing in glucose or ethanol and in the presence of acetic acid. Interesting protein spots were selected using the ANOVA p-value of 0.05 as threshold and 1.5-fold as the minimal level of differential expression, and a total of 53 proteins were successfully identified. Additionally, the size of AAB was reduced by approximately 30% in length as a consequence of the acidity. A modification in the membrane polysaccharides was also revealed by PATAg specific staining.

A Standardized Rotation Thromboelastometry (ROTEM) Method for Evaluation of FVIII and FIX Products in a Multi-National Clinical Trial

Abstract 1199▪▪This icon denotes a clinically relevant abstractMeasurement of FVIII or FIX activity in clinical samples by the one-stage clotting assay is the standard method for estimating the in vivo activity of replacement factor products in the treatment of hemophilia. Global hemostasis assays, such as thromboelastography (TEG) and rotation thromboelastometry (ROTEM) could provide additional information about the in vivo function of FVIII and FIX products since these whole blood assays are thought to more closely reflect in vivo coagulation. However, the TEG and ROTEM assays have not been routinely used in hemophilia care, mainly due to the lack of assay standardization and the absence of reference materials appropriate for hemophilic patient samples. We show here that standardization of the ROTEM assay is possible across multiple sites in a clinical trial. Reproducibility of this method would not only allow ex vivo confirmation of the potency of a novel product in comparison to current replacement factors, but may also reveal patient-specific clotting parameters related to their individual bleeding tendency.We evaluated the effectiveness of a standardized ROTEM procedure in support of Biogen Idec's phase 3 trial of a long-lasting clotting factor IX Fc fusion protein (rFIXFc). Prior to evaluating clinical specimens by ROTEM, each site performed a set of quality control (QC) assays using the ROTROLN reagents provided by TEM Innovations GmbH and a set of frozen plasma controls that were prepared by Biogen Idec by spiking hemophilic plasma with 4 different levels of FIX drug product (1 IU/dL, 5 IU/dL, 15 IU/dL and 30 IU/dL). A detailed protocol and all reagents needed to perform the assay, including custom diluents, were provided to the sites by Biogen Idec in order to ensure a consistent method and reagent lot uniformity across all centers participating in this exploratory study. In addition, local operators at each site participated in hands-on training provided by Biogen Idec.An interim analysis was performed on the QC data gathered from 6 clinical sites that performed a total of 44 QC runs for FIX on 8 ROTEM instruments (7 model Gamma and 1 model Delta). Among the 4 ROTEM parameters evaluated (clotting time, CT; clot formation rate, CFR; maximum clot firmness, MCF and alpha angle), CT was most reproducible, with relatively small variation among the 6 sites, ranging from 8% to 24% CV across the 4 concentration levels of FIX (Table 1).Table 1:Summary of QC INTEM CT data for plasma control samplesGlobal Sites30% FIX (n=12)15% FIX (n=11)5% FIX (n=11)1% FIX (n=10)Mean (sec)901104113422003Min, Max549, 1077907, 12071127, 1737936, 2750%CV17%8%13%24%Biogen Idec Site30% FIX (n1 = 19)15% FIX (n1 = 19)5% FIX (n1 = 19)1% FIX (n1 = 19)Mean (sec)893101012952178Min, Max776, 1002895, 11361033, 16401769, 2837%CV8%7%12%16%A mixed effect model was fitted for the ROTEM global QC data (the response variable) with ‘centers' and ‘plasma FIX levels' as covariates. The center had no statistically significant effect on clotting time (p-value = 0.57) and alpha angle (p-value = 0.85), but a mild impact on MCF (p = 0.12) and CFR (p-value = 0.07). As expected, an increase in FIX concentration level was shown to significantly reduce the clotting times (p-value = 0.001). To further examine our standardization approach in controlling inter-site variability of ROTEM data, two parameters, operator and instrument, were also evaluated. Comparison of the results obtained at the 6 clinical sites to a replicate analysis at a single site (19 runs at each FIX level performed at Biogen Idec by a single operator on 6 model Delta instruments) indicated equivalent variability with an overall ANOVA p-value of 0.85 for CT (accounting for the correlation between ROTEM data and FIX level) and a similar comparability for CFR, MCF and alpha angle.All instruments were maintained within the manufacturer's specification (per ROTROL N data), and there was no instrument-related clustering of results when samples were assayed on multiple instruments at a single site by one operator. We thus conclude that the inter-site variability (i.e. operator and instrument variability) is not a significant factor in our ROTEM study. Assuming the preanalytical variables for the blood collection are also minimized in our standardized procedures, we expect that major differences in a subject's ROTEM parameters will be a meaningful indicator or their hemostatic potential rather than assay variability between individual test sites. Disclosures:Driessler:Biogen Idec Hemophilia: Employment. Li:Biogen Idec Hemophilia: Employment. Liu:Biogen Idec Hemophilia: Employment. Zhang:Biogen Idec Hemophilia: Employment. Jiang:Biogen Idec Hemophilia: Employment. Luk:Biogen idec Hemophilia: Employment. Pierce:Biogen Idec Hemophilia: Employment. Sommer:Biogen Idec Hemophilia: Employment.

Relationship between Peripheral Blood Flow in Extremities and Choroidal Circulation

The aim of this study was to explore the relationship between subjectively estimated and objectively measured finger temperature on the one, and choroidal blood flow on the other side. We measured submacular choroidal blood flow (CBF) in 73 healthy subjects. Based on the history of cold hands and feet, they were divided in three groups, reporting "never", "sometimes" and "always" having cold extremities. As an objective measure of finger temperature, it was recorded at the fingertips with an infrared thermometer (IRT). Analysis of variance for CBF based on the group selection and with blood and intraocular pressures as covariates was performed, as well as the correlation between CBF and IRT. There were 37 subjects in the group with "never" cold extremities, 20 in the group with "sometimes", and 16 subjects in the group with "always" cold extremities. Average age was 44.2 ± 12.9 years. CBF was 11.5 ± 7.3 AU (arbitrary units), 13.6 ± 6.1 AU and 14.3 ± 4.6 AU in the three groups, respectively. The ANOVA p-value was 0.04. Pearson's R for correlation between CBF and IRT was - 0.51, p < 0.001. Subjectively and objectively, colder extremities are associated with higher CBF, possibly due to the redistribution of blood flow.

Statistical Evaluation of Non-Agglomerating Coating for Granulated Natural Asphalt

Agglomeration of granulated Buton natural asphalt during storage is of major concern in its large-scale commercial application. This work develops a simple test method to evaluate the performance of agglomeration-resistant coating for granulated Buton asphalt, consisting of water-based polymeric primary coating and mineral-based secondary coating. The method uses a static load cell to measure the agglomerated granule count fraction under simulated storage conditions. A 2 4-1 fractional factorial experiment with two replications is employed to evaluate the effect of coating drying temperature, drying time, asphalt to secondary coating mass ratio, and secondary coating type on the agglomerated count fraction at ambient temperature and 60 o C. The test is able to measure a statistically significant increase in agglomeration resistance when the coating is applied, with an agglomerated fraction of 17.5% at 60 o C. The test identifies asphalt to secondary coating weight ratio as a significant factor, with an ANOVA p-value much lower than other effects. A decrease in this mass ratio from 5:1 to 5:2 increases the agglomeration, which is hypothesized to be attributed to the hydrated cementitious phase between granular external surfaces. More work is needed to identify the acceptable fraction of agglomerated granules.

Abstract P4-06-17: MRE11/RAD50/NBS1 (MRN) Complex Functions in Invasion in Breast Cells and Tumor Progression

Abstract Background: The MRN complex is essential in conserving genetic integrity. It recruits ATM kinase to damage sites, and distinguishes and activates homologous recombinational repair of DNA double-strand breaks. Individuals with mutations in the MRE11 and NBS1 genes experience radiation sensitivity and are associated with a higher cancer rate. Previously, we showed that some genes involved in DNA repair are involved in regulating cell invasiveness. Since the MRN complex is downregulated in invasive breast cancer, we hypothesize that change in MRN complex expression may contribute to the pre-invasive to invasive progression of breast cancer. Materials and Methods: The HMT-3522 series of breast epithelial cell lines containing non-invasive S1, pre-invasive S3-C, and invasive T4-2 counterparts were used in 2D or 3D culture. Western blot and immunohistochemistry (IHC) were used to determine MRE11, RAD50, and NBS1 expression levels. Breast tumor tissues each containing benign, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) from 48 patients were used after IRB approval. Two pathologists and Ariol, an automated image acquisition and analysis system, scored IHC signal. Tissues were scored 0 to 3 (0=negative, 3=strong positive). ANOVA p-value of .01 or lower was considered significant for expression comparisons. Regression analysis was used for correlating Estrogen Receptor ER/Progesterone Receptor PR status with MRN expression patterns. MRE11, RAD50, and NBS1 were downregulated using siRNA. Protein expression levels were quantified by western blot. Boyden Chamber assay was used to measure cellular invasion through laminin-rich ECM, lrECM (Matrigel). Results: In non-invasive S1 cells, 3DlrECM culturing resulted in higher levels of MRN than in 2D. In pre-invasive S3-C and invasive T4-2 cells, 3DlrECM no longer upregulated MRN. Consequently, in 3DlrECM cultures non-invasive S1 cells had a higher expression of MRE11, RAD50 and NBS1 compared to invasive T4-2 cells. IHC on tissue sections showed that, on average, normal tissues have higher levels of MRN expression than DCIS and DCIS have higher levels of expression than IDC. Multiple MRN expression patterns were observed in subsets of patients when benign, DCIS, and IDC transitions were compared. Decreases in MRN expression correlated with ER/PR negativity: “single decrease” in benign to DCIS to IDC progression was associated significantly with ER negative status for MRE11 and RAD50, not NBS1. MRE11, RAD50, and NBS1 siRNAs downregulated their protein levels in invasive T4-2 cells, resulting in a significant increase in cell invasiveness through ECM. Discussion: First, we described a new role for ECM signaling in up-regulating the DNA repair protein complex MRN in non-tumorigenic cells, which gets misregulated in pre-invasive and invasive cells resulting in a progressive decrease in MRN levels in culture and in tissues. Reciprocally, we showed that downregulation of MRN upregulates invasion through ECM, suggesting it is a negative regulator of invasion in addition to its role as a gatekeeper of genome stability. Finally, different patterns of MRN expression changes in progression associated with ER/PR status suggest MRN levels as a candidate biomarker of patient-specific clinical outcomes. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-06-17.

Phase II randomized study of the safety, efficacy, metabolism, and molecular targets of erlotinib in African Americans (AA) with NSCLC.

7569 Background: We sought to characterize clinical outcomes, EGFR/RAS mutations, EGFR amplification, pharmacokinetics (PK) and pharmacogenetics (PG) in AA patients receiving erlotinib for previously treated NSCLC. Methods: Pts received erlotinib in a phase II 2-stage minimax randomized study, at the standard 150 mg daily (Arm A), or escalated after 1 cycle to achieve skin rash (Arm B). Primary endpoint was disease control rate (DCR, RECIST CR+PR+SD) at 3 months. PBMCs and tumor tissue were collected from all pts to identify SNPs in metabolizing enzymes, and tumor mutations/amplification. PKs from parent drug and active metabolite (OSI-420) were evaluated at days 1 and 28. Results: Of 42 pts randomized, 39 (37 current/former smokers) started erlotinib, 21 on Arm A, 18 on Arm B. DCR at 3 months in 37 pts to date is 32% (30 and 35%, Arms A and B, respectively). Grade ≥3 adverse events included rash (2 pts), and muscle weakness, dyspnea, dehydration, thrombosis, anemia, 1 pt each. No skin rash on the first two months was associated with early PD (10/11). PK analysis in 26 pts showed higher parent drug and metabolite Cmax and AUCs in pts with grades 0-1 vs. grades 2-3 rashes (cycle 2 OSI-420 mean Cmax of 107 ± 83 ng/mL vs. 243 ± 165 ng/mL, respectively; ANOVA p-value = 0.01). SNP presence in CYP3A4 and CYP3A5 also trends with PK, but not statistically significant due to high variability in PK parameter estimates. One EGFR exon 19 short in frame deletion mutation and a novel exon 20 missense R776L (c.2373 G>T) mutation were identified among 28 samples already analyzed. EGFR was amplified in 9/20 samples. 5 pts had Kras mutations: 3 G12C (c.32 G>T), 1 G12D (c.33 G>A), and 1 G12V (c.33 G>T). Silent mutations indicating SNPs in EGFR exon 20 Q787Q (c.2470 G>A) and Kras (-9, C>T), 9 base pairs upstream of the transcription site, were noted. Conclusions: Erlotinib has similar efficacy and toxicity in AA as reported for caucasians. Absence of rash predicted for worst outcome, but the dose-to-rash strategy did not show meaningful differences. PKs, although highly variable, correlate with rash occurrence and may relate to CYP genotype. A larger sample size will be required to evaluate the role of the PBMC/tumor SNPs identified. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech

Determinants of smoking initiation among women in five European countries: a cross-sectional survey

BackgroundThe rate of smoking and lung cancer among women is rising in Europe. The primary aim of this study was to determine why women begin smoking in five different European countries at different stages of the tobacco epidemic and to determine if smoking is associated with certain characteristics and/or beliefs about smoking.MethodsA cross-sectional telephone survey on knowledge and beliefs about tobacco was conducted as part of the Women in Europe Against Lung Cancer and Smoking (WELAS) Project. A total of 5 000 adult women from France, Ireland, Italy, Czech Republic, and Sweden were interviewed, with 1 000 from each participating country. All participants were asked questions about demographics, knowledge and beliefs about smoking, and their tobacco use background. Current and former smokers also were asked questions about smoking initiation. Basic statistics on the cross-sectional data was reported with chi-squared and ANOVA p-values. Logistic regression was used to analyze ever versus never smokers. Linear regression analyses were used to analyze age of smoking initiation.ResultsBeing older, being divorced, having friends/family who smoke, and having parents who smoke were all significantly associated with ever smoking, though the strength of the associations varied by country. The most frequently reported reason for initiation smoking was friend smoking, with 62.3% of ever smokers reporting friends as one of the reasons why they began smoking. Mean age of smoking initiation was 18.2 years and over 80% of participants started smoking by the age of 20. The highest levels of young initiators were in Sweden with 29.3% of women initiating smoking at age 14-15 and 12.0% initiating smoking younger than age 14. The lowest level of young initiators was in the Czech Republic with 13.7% of women initiating smoking at age 14-15 and 1.4% of women initiating smoking younger than age 14. Women who started smoking because their friends smoked or to look 'cool' were more likely to start smoking at a younger age. Women who started smoking to manage stress or to feel less depressed were more likely to start smoking at an older age.ConclusionsIn all five participating countries, friends were the primary factor influencing ever smoking, especially among younger women. The majority of participants began smoking in adolescence and the average reported age of smoking initiation was youngest in Sweden and oldest in the Czech Republic.

An Assessment Of Compliance Of Building Construction Projects With Environmental Impact Assessment Requirements In Nigeria

Nigeria recorded and has continued to witness collapse of structures in recent times, most of which are building structures characterized with eventual loss of life and property. The rigorous construction activities in Nigeria bear direct and indirect impacts on the environment by displacement of communities and destruction of their farmlands and economic trees, among other things. These pose threats to the existence of man and the sustenance of natural vegetation. Environmental Impact Assessment (EIA) is encapsulated as a practicable management tool designed to address likely environmental problems that may develop on the construction processes. The EIA decree in Nigeria enacted in 1992 stipulates mandatory implementation in some special projects including building projects. However, statistics obtained with the Federal Ministry of Environment show that the level of its activities is not significant as at June 2006. A regression analysis revealed an ANOVA p-value of 0.030, less than the critical value of significance (0.050). The concerns generated as the result of this therefore, require a deliberate strategy of integrating EIA in the processes of project cycles. For an appreciable level of implementation, the allied professionals involved in the process should be updated with the workings and current challenges of EIA.

A simulation-based approach to evaluate population stratification in Argentina

The analysis of STR (short tandem repeat) markers typically used in forensic genetics has shown that substantial level of population stratification exists across different urban populations; nevertheless, most of the differences between any pair of urban populations reside in a few markers. In order to determine to what extent there is a real impact in forensic casework, we performed a comparison of CLRs (combined likelihood ratios) of 1906 genetic profiles from 8 different populations from Argentina. CLRs were computed using 15 and 5 STRs and 8 different (reference) population frequency databases. A random sampling of individuals in each population was performed in order to generate a mean value and standard deviations for the CLRs of every profile. One-way-ANOVA and a post hoc test (Dunnet) were applied to assess the significance of the differences between the mean CLRs values. ANOVA P-values lower than 0.05 were obtained in different proportions of the comparisons for each population. Differences were most notable when comparing CLRs from urban populations with those from native populations, and appeared to become more important when comparing 5-STRs CLRs. Results are consistent with previous findings on population stratification and support the use of local reference databases in forensic casework.

An experimental model for the measurement of inspired gas temperatures in ventilated neonates

To determine the inspired gas temperature at points from the endo-tracheal tube (ETT) circuit manifold to the tip of the ETT in a model neonatal lung. A model lung attached to standard ventilator circuit, autofeed chamber and humidifier was ventilated using typical pressure-limited, time cycled settings. Temperatures were measured at various distances along the ETT using a K-type thermocouple temperature probe. The inspired gas temperature dropped from the circuit temperature probe site (40 degrees C) to the proximal end of the ETT (37 degrees C). The temperature dropped further as it passed through the exposed part of the ETT (34 degrees C) but then warmed again on entering the lung model so that the inspired gas at the distal end of the ETT was 37 degrees C. Statistically significant differences were found with a one-way ANOVA P-value of <0.0001. The differences between each pair of mean temperatures were statistically significant (all P<0.001) except when comparing the proximal end of the ETT with midway down the ETT (Bonferroni's Multiple Comparison Test, P>0.05). Inspired gas temperature drops as it passes through the circuit temperature probe site, the proximal end of the ETT and the exposed part of the ETT. The inspired gas rewarms on entering the model lung and exits the ETT at the desired temperature. The effect of measuring temperature closer to the patient, setting the circuit temperature higher and/or increasing the ambient temperature through which the circuit passes, need to be evaluated.

DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage

Epigenetic changes have been implicated in the pathogenesis of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Prior efforts have primarily examined regional promoter hypermethylation as a silencer of tumor suppressor gene expression. To analyze the global state of methylation in the HNSCC genome, we utilize pyrosequencing of repetitive elements (LINEs) to compare the state of global methylation in HNSCC to normal aerodigestive mucosa. 137 samples (119 HNSCC tumors and 18 normal mucosal tissues) were digested to extract DNA and subjected to bisulfite treatment. Treated DNA was amplified using PCR primers for the repetitive LINEs sequence and produced a heterogeneous sample of products, from many genomic loci. These products were pyrosequenced to quantitatively evaluate their global genomic methylation status. HNSCC specimens showed global hypomethylation, with a mean level of genomic methylation of 46.8% methylated with a standard deviation of 9.0. Conversely, the normal upper airway mucosa had a global methylation level of 54.0 and a standard deviation of 4.6 (Mann-Whitney p value < 0.001). The tumor specimens also showed an increasing degree of hypomethylation associated with advanced tumor stage (ANOVA p-value of 0.003). About 67% of HNSCC's are globally hypomethylated when evaluated against the minimum level of methylation in the normal mucosal specimens. Degree of global hypomethylation was associated with smoking history, alcohol use and stage in univariate analysis (p-value 0.02), however, only HNSCC diagnosis remained significant on multivariate analysis. Despite the presence of regional promoter hypermethylation, HNSCC demonstrates global genomic hypomethylation. The effects of stage, alcohol use and smoking on global hypomethylation were not independently significant.

Disabilities of the Arm, Shoulder and Hand (Dash) Questionnaire: Determining Functional Activity Profiles in Patients with Upper Extremity Disorders

The Disability of Arm, Shoulder and Hand (DASH) questionnaire is a standardized measure which captures the patients' own perspective of their upper extremity health status. Based on the scores of the DASH modules: symptoms, function and sport, this follow-up study of 590 hand-injured subjects from 11 diagnostic groups evaluated impairments and disabilities perceived 2 to 5 years postoperatively. Secondly, we explored the relationships between the diagnostic groups at the individual DASH item level. Exploratory testing of statistical significance showed that the DASH modules differentiated well among the groups (ANOVA P-value 0.001) and further differences existed at the item level, so that functional activity problem profiles could be developed for each diagnostic group. Our findings confirm that the DASH is a useful instrument for outcome evaluation. Moreover, in view of the continuing challenge to provide comprehensive care which meets patients' needs in the shortest space of time, we consider that DASH has potential in the development of patient-centred treatment programmes which are tailored to the individual patients' requirements and have relevance to their daily activities.

Peripheral Neuropathy And Macro-Angiopathy In Diabetics With Foot Ulcers In Port Harcourt, Nigeria

OBJECTIVES: The study was aimed to determine the prevalence of peripheral neuropathy and macro-angiopathy among adult diabetic subjects with foot ulcer/gangrene in Port Harcourt, Nigeria. METHODS AND MATERIALS: Fifty-one (51) consecutive diabetics with foot ulcer/gangrene admitted into the medical wards of the University of Port Harcourt Teaching Hospital (UPTH) between January 2002 and April 2003, were evaluated for symptom and signs of peripheral neuropathy. Symptoms and signs grades were assigned using a modification of the scoring system developed by Young et al (1993). Peripheral macro-vascular disease was assessed by palpation of the dorsalis pedis and posterior tibial arteries. RESULTS: Thirty eight (74.5%) of the subjects had symptoms of peripheral neuropathy of mild to severe grades, and forty four (86.3%) had signs of neuropathy of mild to severe grades. Seven (13.7%) of the subjects had neither symptoms nor signs, while six (11.8%) had asymptomatic peripheral neuropathy. Overall, symptom and sign ratings showed poor agreement (Kappa Coefficient=0.335). The mean duration of diabetes was directly related only to symptoms grade (ANOVA p-value=0.02). Eighteen (35.3%) of the subjects had absence of either the dorsalis pedis or the posterior tibial pulses in the affected foot. Of these, 15 (83.3%) also had co-existing signs of peripheral neuropathy; the rest 3 (16.7%) had absent pulses only. CONCLUSIONA high prevalence of peripheral neuropathy in diabetics with foot ulcers/gangrene was recorded. The study also revealed that peripheral vascular disease alone may not play a major role in the aetiology of diabetic foot ulceration; further strengthening the important role of peripheral neuropathy in the aetio-pathogenesis of diabetic foot ulcers. We recommend early screening for peripheral neuropathy, in addition to meticulous foot care, and improved glycaemic control. KEY WORD: Peripheral neuropathy, Macro-angiopathy, Diabetic foot ulcers, Nigeria Nigerian Journal of Orthopaedics and Trauma Vol.3(2) 2004: 214-224

O3-02-03 Heritability of psychosis in Alzheimer disease

MicroRNAs (miRNAs) are small non-coding RNAs that act as potent regulators of gene expression. A recent GWAS reported the rs1625579 SNP, located downstream of miR-137, as the strongest new association with schizophrenia [Ripke S, Sanders AR, Kendler KS, Levinson DF, Sklar P, Holmans PA, et al. Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011;43:969–76.]. Prior to this GWAS finding, a schizophrenia imaging-genetic study found miR-137 target genes significantly enriched for association with activation in the dorsolateral prefrontal cortex (DLPFC) [Potkin SG, Macciardi F, Guffanti G, Fallon JH, Wang Q, Turner JA, et al. Identifying gene regulatory networks in schizophrenia. Neuroimage 2010;53:839–47.].We investigated the expression levels of miR-137 and three candidate target genes (ZNF804A, CACNA1C, TCF4) in the DLPFC of postmortem brain tissue from 2 independent cohorts: (1) 26 subjects (10 control (CTR), 7 schizophrenia (SZ), 9 bipolar disorder (BD)) collected at the UCI brain bank; and (2) 99 subjects (33 CTR, 35 SZ, 31 BD) obtained from the Stanley Medical Research Institute (SMRI). MiR-137 expression in the DLPFC did not differ between diagnoses. We also explored the relationship between rs1625579 genotypes and miR-137 expression. Significantly lower miR-137 expression levels were observed in the homozygous TT subjects compared to TG and GG subjects in the control group (30% decrease, p-value = 0.03). Moreover, reduced miR-137 levels in TT subjects corresponded to increased levels of the miR-137 target gene TCF4. The miR-137 expression pattern in 9 brain regions was significant for regional effect (ANOVA p-value = 1.83E-12), with amygdala and hippocampus having the highest miR-137 expression level. In conclusion, decreased miR-137 expression is associated with the SZ risk allele of rs1625579, and potential regulation of TCF4, another SZ candidate gene. This study offers additional support for involvement of miR-137 and downstream targets as mechanisms of risk for psychiatric disorders.

Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients.

Serum ferritin is a frequently used marker of iron status in dialysis patients. Iron administration is to be withheld for ferritin values >800 ng/ml according to K/DOQI guidelines. We hypothesized that such non-iron-related factors as elements of the malnutrition-inflammation complex syndrome (MICS) may increase serum ferritin concentration independently of iron status. We studied 82 prevalent maintenance haemodialysis (MHD) patients (including 43 men), aged 55.7 +/- 15.3 years. The inflammatory and nutritional status was evaluated by serum C-reactive protein (CRP), Subjective Global Assessment (SGA) and its newer, fully quantitative versions, i.e. Dialysis Malnutrition Score (DMS) and Malnutrition-Inflammation Score (MIS). All but six patients had been on maintenance doses of intravenous iron dextran (between 100 and 200 mg/month) during the 10 weeks prior to the measurements. Serum ferritin levels were increased across SGA categories: (ANOVA P-value 0.03). Both unadjusted and multivariate adjusted correlation coefficients (r) for serum ferritin and CRP vs pertinent values were statistically significant for DMS and MIS and some other measures of nutritional status and iron indices. After deleting 10 MHD patients with either iron deficiency (ferritin <200 ng/ml) or iron overload (ferritin >2000 ng/ml), in the remaining 72 MHD patients both bivariate and multivariate correlations were much stronger and statistically significant (r = -0.33 and -0.29, respectively, P < 0.01). A multivariate model showed simultaneous, significant correlations between serum ferritin and both markers of inflammation and iron status independent of each other. After dividing the 72 MHD patients into two groups of serum ferritin based on a K/DOQI recommended serum ferritin cut-off of 800 ng/ml, the MIS and logarithm of serum CRP were significantly higher in the higher ferritin group. Serum ferritin values in the range of 200-2000 ng/ml may be increased due to non-iron-related factors including elements of MICS.

REPRODUCIBILITY OF ISOMETRIC AND ISOKINETIC TESTING OF ANKLE PLANTAR FLEXION STRENGTH AND ENDURANCE

142 Use of isometric and isokinetic strength measurements has helped many athletic trainers, exercise physiologists, physical therapists, and others to reliably measure voluntary production of force, power, torque and work. Although there have been ample studies concentrated on the knee, quadriceps, shoulder, and back, the reliability of the ankle has not been well studied. The purpose of this research was to conduct reproducible strength measurements of ankle plantar flexion over a 10 week period. Seven healthy subjects, ranging in physical activity from moderate to active, were studied. The subjects were tested on three different occasions: week 1 (W1), week 5 (W5), and week 10 (W10). The neutral position (0 °) was set at a 90 ° angle between the foot and the tibia. Maximal isometric strength was tested with the ankle at the defined 0 ° neutral position and at 10 ° plantar flexion. Maximal voluntary contractions (MVCs) were performed for 5 seconds. Isokinetic contractions were performed between the neutral position and the maximal plantar flexion position that the subjects experienced as being comfortable. Isokinetic strength was measured at angular velocities of 30, 60, 120 and 180 degrees/sec. Maximal isokinetic endurance was tested by monitoring fatigue and total work done over 50 repeated isokinetic plantar flexions at 60 °/sec. ANOVA statistics showed little variation between isometric and isokinetic measurements taken at each time point. The average p-value of isometric and isokinetic plantar flexion was 0.0039±0.0012 and 0.0791±0.0415, respectively. The isokinetic endurance test, however, showed a significant amount of variance between time points; ANOVA p-values in peak torque and work were 0.7779±0.1300 and 0.5549±0.1182, respectively. This study suggests that measurement of isometric and, to a lesser extent, isokinetic MVCs can potentially be used as a reliable, diagnostic tool to monitor patients' rehabilitation and recovery of strength following ankle joint trauma, disuse and consequent skeletal muscle atrophy in surrounding plantar flexors.

The efficacy of high impact incarceration: A correctional treatment outcome study

The objective of this research was to determine the treatment outcome for a group of adult male city-sentenced inmates and parole violators in a High Impact Incarceration Program (HIIP) “boot camp”. The research design was a quasi-experimental, one-group, pretest/posttest design without a control group (APA, 1982). The setting for the study was the new York City Department of Correction High Impact Incarceration Program (HIIP) on Rikers Island. The participants consisted of thirty-three (33) adult male city-sentenced inmates and parole violators who volunteered to participate in the rigorous boot camp program. The High Impact Incarceration Program (HIIP) was the experimental/independent variable for this study as well as the treatment intervention that was utilized in this research. The outcome measure was the Carlson Psychological Survey (CPS). The research question for this study was: What, if any, change(s) in personality disorder and its comorbid factors (dependent variable) take place in the inmate/subject after a period of high impact incarceration? The intervention (HIIP) lowers the pre to post level means of four (4) of the five (5) variables. Two of the four decreases are significant: Chemical Abuse (CA) and Self-Depreciation (SD), with the latter being highly significant (ANOVA P-Value of 0.0000). The largest of the four decreases is 27%. The fifth variable—Validity—(V) is unaffected by the intervention with pre and post means of 3.394 and 3.409, respectively. The variable Antisocial Tendencies (AT) comes near to significance with a confidence of .0677. Though Disturbance (TD) proved unaffected by the intervention. HIIP appears to be significantly effective in changing certain personality factors and their comorbid factors while the teammates (inmates) are within this intensive, rigorous, and highly structured program. Further research is necessary to determine what effect this personality change has on the rate of recidivism.

967-20 Reduced Thrombogenicity of Nitinol vs Stainless Steel Slotted-Tube Stents in Rabbit Carotid Arteries

The thrombogenicity of slotted-tube stents made of nitinol or stainless steel (Palmaz Schatz) was assessed in a rabbit carotid artery model. Fourteen nitinol and 8 stainless steel stents (7 mm long single segment stents) were deployed in a carotid artery of 22 NZW rabbits with a 3.0 mm balloon inflated twice at 6 atm for 1 min. No antiplatelet or antithrombotic drugs were given. Eight rabbits with nitinol and 8 with stainless steel stents were euthanized after 4 days. The remaining 6 rabbits with nitinol stents were euthanized after 14 days. At sacrifice, both carotids (stented and control) were exposed and resting blood flow measured. The amount of thrombus on each stent was assessed by a semi-quantitative grading scale (I: no lumen encroachment; II: lumen encroachment; III: subocclusive thrombus; and IV: occlusive thrombus) and by the weight of the dry thrombus. All nitinol were patent at 4 and 14 days whereas 6 out of 8 (75%) stainless steel stents had total thrombotic occlusion at 4 days (p &lt; 0.0001). Parameter Stainless Steel 4 day Nitinol 4 day Nitinol 14 day ANOVA p-value n 8 8 6 Carotid flow (ml/min) 1.5 ± 2.8 24.0 ± 2.0 25.5 ± 19 &lt;0.000001 Thrombus grade III = 2, IV = 6 I = 8 I = 6 &lt;0.0001 Thrombus weight (mg) 20.0 ± 5.9 2.5 ± 0.6 2.7 ± 0.3 &lt;0.000001 Histologic examination of stented arterial segments showed that although the depth of strut penetration was similar in all 4 day rabbits, the group with stainless steel stents consistently had evidence of diffuse medial necrosis and thinning (8/8 vs 118; P = 0.0004). Nitinol stents developed significantly less thrombus in comparison to stainless steel stents of similar design as measured by thrombus weight. thrombus grade and degree of blood flow reduction at 4 days in the rabbit carotid artery model. For nitinol stents there was no worsening of these thrombotic parameters at 14 days, compared to 4 days. More severe vascular injury may contribute to the thrombogenicity of stainless steel stents.

ANALYSIS OF A TWO LACTATION TARGET ANIMAL SAFETY STUDY OF SOMIDOBOVE SUSTAINED RELEASE INJECTION IN MULTIPAROUS DAIRY COWS

An overview is given of the primary basis for the scientific inference that somidobove sustained release injection is safe for multiparous dairy cows. The process of analysis and interpretation of the voluminous data collected from a target animal safety study which started with 28 cows and lasted two lactations is described. This was a repeated measures study with most of 60 variables being measured or summarized every 28 days resulting in approximately 1500 measurements per cow. The statistical analysis was designed to screen the variables for biological change caused by treatment and consisted of a univariate analysis of variance for repeated measures data both within a lactation and across two lactations. Graphs of least squares means with error bounds and p-value plots of ANOVA p-values helped communicate statistical findings. A cross disciplinary approach interpreted analyses and arrived at inferences.