Effect of manganese preconditioning and replacing inorganic manganese with organic manganese on performance of male broiler chicks.

The effects of manganese (Mn) preconditioning, 96 h post-hatch followed by the replacement of inorganic Mn with different levels of organic Mn (5 to 21 D), on growth, tissue excreta Mn content, gene expression, and enzyme activity were evaluated. A total of 420 day-old male Cobb 500 broilers were divided into 2 groups. One group was fed a corn-soybean meal basal diet containing 17 mg of Mn/kg (preconditioning diet, MnPD); the second group was fed the non-preconditioning diet (NPCD), which was the MnPD supplemented with 60 mg of Mn/kg from manganese sulfate (MnSO4). On day 5, each group was divided into 5 subgroups and were randomly assigned to dietary treatments consisting of MnPD alone or MnPD supplemented with 12 or 60 mg Mn/kg Mn as MnSO4 or Mn proteinate (6 replicate cages of 6 birds). Broiler chicks that were fed the MnPD had lower (P ≤ 0.05) body weight gain (BWG) and G:F ratio when compared to those that were fed the NPCD for 4 D. Birds that were fed MnPD (1 to 4 D) and switched to MnPD supplemented with 60 mg/kg Mn (5 to 21 D) had lower (P ≤ 0.05) BWG compared to those that were fed NPCD (1 to 4 D) and switched to MnPD supplemented with 60 mg/kg Mn for 21 D. Excreta, tibia ash, liver, and heart Mn levels were increased (P ≤ 0.05) by supplemental Mn. The expression of jejunum divalent metal transporter-1 mRNA levels, as well as activities of plasma total super oxide dismutase and liver alanine transaminase, was not affected by MnPD or Mn source and levels. These results confirmed that feeding marginally deficient Mn diets to broiler chicks post-hatch does affect growth rate and tissue Mn concentration.

Effect of zinc imprinting and replacing inorganic zinc with organic zinc on early performance of broiler chicks.

The goal of this study was to determine the effects of feeding a zinc (Zn) deficient diet to broiler chicks for 96 h post-hatch followed by feeding diets with different Zn sources and supplemental levels (5 to 21 d) on the growth performance, tissue, and excreta Zn content. At the start of the study, four hundred 20-day-old male broiler chicks were divided into two groups. One group was fed a corn soybean meal based diet containing 25 mg of Zn/kg (imprinting diet, ID). The second group was fed the basal diet supplemented with 40 mg of Zn/kg from Zn oxide (ZnO) (non-imprinting diet, NID). Both groups were fed these diets for 96 h. At d 5, chicks from each group were randomly assigned to the dietary treatments consisting of the basal diet alone or the basal diet supplemented with 8 or 40 mg/kg Zn as ZnO or Zn proteinate. Main effects of post-hatch Zn ID were observed on feed intake and G:F. ID decreased (P < 0.05) feed intake and improved (P < 0.05) the gain to feed ratio (G:F) of 14 and 21 d old chicks compared to G:F of chicks fed NID. Additionally, G:F for 14 and 21 d was improved (P < 0.05) by interaction of Zn source × level. Furthermore, at d 21 chicks fed the ID had a lower (P < 0.05) Zn content in the tibia ash and excreta, and a higher (P < 0.05) Zn content in the pancreas tissue compared to chicks fed NID. These results suggest that Zn imprinting can affect body Zn stores and early performance.

Contextual factors influencing the implementation of the obstetrics hemorrhage initiative in Florida.

OBJECTIVE: The purpose of this study was to explore the multilevel contextual factors that influenced the implementation of the Obstetric Hemorrhage Initiative (OHI) among hospitals in Florida. STUDY DESIGN: A qualitative evaluation was conducted via in-depth interviews with multidisciplinary hospital staff (n=50) across 12 hospitals. Interviews were guided by the Consolidated Framework for Implementation Research and analyzed in Atlas.ti using rigorous qualitative analysis procedures. RESULT: Factors influencing OHI implementation were present across process (leadership engagement; engaging people; planning; reflecting), inner setting (for example, knowledge/beliefs; resources; communication; culture) and outer setting (for example, cosmopolitanism) levels. Moreover, factors interacted across levels and were not mutually exclusive. Leadership and staff buy-in emerged as important components influencing OHI implementation across disciplines. CONCLUSION: Key contextual factors found to influence OHI implementation experiences can be useful in informing future quality improvement interventions given the institutional and provider-level behavioral changes needed to account for evolving the best practices in perinatology.

Organic trace mineral levels in the first 96-h post-hatch impact growth performance and intestinal gene expression in broiler chicks.

Alterations in nutrient intake in the avian neonatal posthatch period can impact development, performance, and metabolism in adulthood. Very little is known about how mineral levels during the post-hatch period affect or "program" gene expression patterns later in life. The objective of this study was to determine the effect of post-hatch (0 to 96 h) dietary mineral supplementation on performance, tissue mineral content, and intestinal gene expression profiles in 21-day-old broiler chicks. One-day-old chicks were randomly assigned to one of two treatment groups consisting of N (organic Zn, Cu, and Mn provided at 100 % of recommendations (National Research Council 1994)) and/or L (organic Zn, Cu, and Mn provided at 20 % of recommendations (National Research Council 1994)) diets fed in two intervals (days 1­4, days 5­21) as follows: (1)N­Lor (2)L­L. Performance parameters did not differ between treatments except that body weight gain was greater (P < 0.05) in L­L birds than N­L birds over the experimental period. Bone mineral content was similar for both treatments at day 21. Intestinal gene expression profiling was examined using the Affymetrix GeneChip Chicken genome array. Ingenuity pathway analysis revealed differences in gene expression profiles between N and L treatments at day 5. At day 21, profiles were unique between N­L and L­L, suggesting that the diet fed until day 4 had an impact on gene expression patterns at day 21 even when birds were fed the same diets day 5­day 21. In this study, we demonstrated that diets fed for the 96 h post-hatch had long-term effects on gene expression, providing unique information as to why post-hatch diets are so important for the longterm bird health and productivity.

Effects of yeast cell wall-derived mannan-oligosaccharides on jejunal gene expression in young broiler chickens.

The use of mannan-oligosaccharides (MOS) as alternatives to antibiotic growth promoters (AGP) has gained in popularity in recent years due to regulatory restrictions of using AGP in food animal production. Benefits of MOS usage include improvement on animal performance, feed efficiency, and gastrointestinal health. The molecular mechanisms of these functions however are not clear. The goal of the current study was to use a transcriptomics approach to investigate the effects of MOS on the intestinal gene expression profile of young broilers and characterize biological gene pathways responsible for the actions of MOS. One hundred and twenty 1-d-old Cobb 500 broiler chicks were randomly divided into 2 groups and were fed either a standard wheat-soybean meal-based (control) diet or the same diet supplemented with 2.2 g/kg of MOS (Bio-Mos, Alltech, Nicholasville, KY) for 3 wk, followed by jejunal gene expression profiling analysis using chicken-specific Affymetrix microarrays. Results indicated that a total of 672 genes were differentially expressed (P < 0.01 and fold change >1.2) in the jejunum by MOS supplementation. Association analysis indicated that differentially expressed genes are involved in diverse biological functions including energy production, cell death, and protein translation. Expression of 77 protein synthesis-related genes was differentially regulated by MOS in the jejunum. Further pathway analysis indicated that 15 genes related to oxidative phosphorylation were upregulated in the jejunum, and expression of genes important in cellular stress response, such as peroxiredoxin 1, superoxide dismutase 1, and thioredoxin, were also increased by MOS. Differential expression of genes associated with cellular immune processes, including lysozyme, lumican, ß 2-microglobin, apolipoprotein A-1, and fibronectin 1, were also observed in MOS-fed broilers. In summary, this study systematically identified biological functions and gene pathways that are important in mediating the biological effects of MOS in broilers.

Effects of feeding different concentration and forms of zinc on the performance and tissue mineral status of broiler chicks.

1. Two studies were conducted to investigate the effect of feeding different concentration and forms of zinc (Zn) on the performance and tibia Zn status of broiler chicks. 2. In Experiment 1, chicks fed on the control or the diet supplemented with 12?mg of Zn as sulphate had lower feed intake, weight gain and tibia Zn content than other treatment groups. Chicks given 12 and 24 mg of organic Zn in starter and grower phases, respectively, had the same performance and tibia Zn content as those fed 40 mg of Zn as sulphate and the same performance but higher tibia Zn content than those given 12 mg of Zn as organic over the 42 d. 3. In Experiment 2, chicks given 24 mg organic Zn had greater weight gain than chicks fed on the other treatment diets in the starter period. Chicks fed on the control diet had lower tibia Zn content than chicks fed other treatment diets. Chicks given 80 mg Zn as sulphate had higher tibia Zn content than chicks fed the other treatment diets except those given 40 mg of Zn as sulphate. 4. The results from these trials indicate that feeding lower concentration of Zn as organic form may better promote the growth performance of broiler chicks.

Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields.

BACKGROUND: Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies. METHODS: A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival 6 months. Secondary efficacy end points were progression-free survival and overall survival. RESULTS: Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1-5.3) and median overall survival was 6.7 months (95% CI 3.0-10.2). There were three partial and one near complete responses. CONCLUSION: Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC.

Effects of organic and inorganic dietary selenium supplementation on gene expression profiles in oviduct tissue from broiler-breeder hens.

Selenium (Se) is an essential component of at least 25 selenoproteins involved in a multitude of physiological functions, including reproduction. However, relatively little is known about the mechanisms by which Se exerts its physiological effects in reproductive tissue. The objective of this study was to compare the effect of long-term inorganic Se (sodium selenite, SS) and organic yeast-derived Se (Sel-Plex(®), SP) supplementations on tissue Se content and gene expression patterns in the oviduct of broiler-breeder hens. Hens were randomly assigned at 6 weeks of age to one of the three treatments: basal semi-purified diet (control), basal diet+0.3 ppm Se as SP or basal diet+0.3 ppm Se as SS. At 49 weeks, oviduct tissue from hens randomly selected from each treatment (n=7) was analyzed for Se content and gene expression profiles using the Affymetrix Chicken genome array. Gene expression data were evaluated using GeneSpring GX 10.0 (Silicon Genetics, Redwood, CA) and Ingenuity Pathways Analysis software (Ingenuity Systems, Redwood City, CA). Oviduct Se concentration was greater with Se supplementation compared with the control (P≤0.05) but did not differ between SS- and SP-supplemented groups. Gene expression analysis revealed that the quantity of gene transcripts associated with energy production and protein translation were greater in the oviduct with SP but not SS supplementation. Targets up-regulated by SP, but not SS, included genes encoding several subunits of the mitochondrial respiratory complexes, ubiquinone production and ribosomal subunits. SS hens showed a decrease in transcripts of genes involved in respiratory complexes, ATP synthesis and protein translation and metabolism in oviduct relative to control hens. In this study, although tissue Se concentrations did not differ between hens fed SS- and SP-supplemented diets, expression patterns of genes involved in energy production and protein synthesis pathways differed between treatments. These variations may partially explain the differences in reproductive performance reported in hens fed different forms of Se.

Effects of feeding different forms of zinc and copper on the performance and tissue mineral content of chicks.

A study was conducted to investigate the effects of feeding inorganic or organic Zn and Cu on the performance and tissue mineral content of chicks. A corn-soybean meal diet without Cu and Zn supplementation, containing 31 mg of Zn/kg of diet and 6.6 mg of Cu/kg of diet, was used as a basal diet. Organic Zn (a chelated Zn proteinate) and organic Cu (a chelated Cu proteinate) were used as organic sources for comparison with inorganic reagent-grade sulfates. Supplements provided 20 mg/kg of Zn and 8 mg/kg of Cu. A 3x3 factorial arrangement of treatments consisting of feeding the basal diet with 3 supplements (none, sulfate, or organic) of Cu and of Zn was used. Ten groups of 6 one-day-old male broilers were assigned to each of 9 dietary treatments. Tap water and feed were supplied on an ad libitum basis during the 3-wk trial. The Zn and Cu content in the mucosa of the duodenum of the chick was determined. Dietary supplementation of Zn increased (P<0.01) weight gain, feed intake, and G:F of chicks. The G:F for chicks fed both inorganic sources of Zn and Cu was lower (P<0.01) than that for chicks fed only the inorganic source of Zn. Dietary inclusion of Zn increased (P<0.01) tibia and plasma Zn content. The tibia Zn content for chicks fed organic Zn was higher (P<0.01) than that for chicks fed inorganic Zn. Liver Cu content was decreased (P<0.05) by dietary inclusion of Zn. The Zn and Cu contents in the mucosa of chicks fed the organic source were higher (P<0.01) than those of chicks fed the control diet. The feed conversion data suggest that the antagonism between Zn and Cu occurred when the inorganic forms, but not organic forms, of these 2 minerals were included in a chick diet.

Effect of enzyme supplementation and acidification of diets on nutrient digestibility and growth performance of broiler chicks.

Two experiments were conducted to examine the effects of alpha-galactosidase supplementation and acidification of diets on nutrient digestibility and growth performance of broiler chicks. In experiment 1, dietary treatments consisted of feeding a low-energy basal diet (2.74 Mcal of ME/kg) alone, the basal diet supplemented with 1,724 units of alpha-galactosidase per kg, the basal diet supplemented with 2% citric acid, or the basal diet supplemented with both. alpha-Galactosidase significantly increased feed intake, weight gain, AME(n) of the diets, and retention of CP and neutral detergent fiber (NDF) (P < 0.05). Citric acid significantly increased the retention of DM, CP, and NDF, but decreased feed intake and weight gain. The greatest values for DM and NDF retention and for AME(n) were obtained with the combination of alpha-galactosidase plus citric acid. In experiment 2, chicks were fed diets with 2 levels of energy (2.74 or 3.11 Mcal/kg), 2 levels of citric acid (0 or 1.5%), and 2 levels of alpha-galactosidase (0 or 1,724 units/kg) in a 2 x 2 x 2 factorial arrangement of treatments. alpha-Galactosidase significantly increased the reducing sugar concentration in the crop content, whereas citric acid decreased the pH and increased the reducing sugar concentration in the crop content. Citric acid decreased the gain to feed ratio in the absence but not in the presence of alpha-galactosidase. The data from these studies indicate that acidification of diet improves the efficacy of alpha-galactosidase.

Effects of organic zinc and phytase supplementation in a maize-soybean meal diet on the performance and tissue zinc content of broiler chicks.

1. The purpose of this study was to investigate the effects of Bioplex Zn (a chelated zinc proteinate) and phytase supplementation in a maize-soybean meal diet on the performance and tissue zinc (Zn) content of broiler chicks. Treatment structure consisted of a 2 x 6 factorial arrangement with two inclusions of phytase (0 or 500 PU/kg) and 6 of Bioplex Zn providing 0, 2, 4, 8, 16 and 32 mg Zn/kg diet. A total of 864 chicks were randomly assigned to each of 12 dietary treatments with 6 replicate cages of 12 chicks. 2. Dietary inclusion of phytase increased feed intake, weight gain, plasma Zn content, tibia Zn content, tibia and ash weight. 3. Dietary supplementation of Bioplex Zn linearly increased feed intake, weight gain, gain to feed ratio, plasma Zn concentration, liver Zn concentration, tibia Zn content, tibia and ash weight. 4. An interactive effect of phytase and Bioplex Zn on feed intake, weight gain, tibia Zn concentration and tibia ash weight was found. 5. One slope, straight broken-line analysis of weight gain regressed on the supplemental Zn level provided as Bioplex Zn indicated that 12 mg/kg supplemental Zn without phytase and 7.4 mg/kg supplemental Zn with phytase were required for the optimal weight gain of chicks.

A global genome damage score predictive of lung cancer patients outcome.

Genome damage is a hallmark of human cancer. Efforts at assessing the impact of genome damage on tumor phenotype and patients outcome have focused on measurements of the relative DNA content in tumor cells compared to normal cells and the assessment of allelic loss at single or multiple selected loci that are thought to harbor genes important in cancer biology. We adapted a global, high-resolution genotyping method for determination of global and unbiased allelic loss. We generated a score, termed global genome damage score (GGDS), that is a continuous variable from zero to one and a measure of the extent of damaged DNA in individual tumors. In 71 patients with completely resected non-small-cell lung cancer, the GGDS ranged from 0.0006 to 0.5530 with a median value of 0.0401 indicating that between 0.06 and 55.3% of the genome has allelic loss. Patients with high scores (>0.04) had a significantly worse outcome than those with low scores (median overall survival time 35.5 vs >120.0 months, P=0.006 log-rank test; median disease-free survival 28.3 vs >120.0 months, P=0.003 log-rank test). This suggests that the clinical behavior of lung tumors with low GGDS is relatively benign whereas tumors with high GGDS are aggressive resulting in early death of patients.

A multi-institutional study of orthotopic neobladders: functional results in men and women.

OBJECTIVES: To analyse the incidence of diurnal incontinence (DI) and nocturnal incontinence (NI), the need for intermittent catheterization (IC),and the rate of ureteric obstruction (UO) among a group of men and women with ileal and colonic orthotopic neobladders in four countries. PATIENTS AND METHODS: In all, 138 patients (113 men and 25 women) had an orthotopic neobladder constructed after radical cystectomy for carcinoma. The mean(range) age was 61.3 (28-76) years and the follow-up 41 (6-144) months. All patients underwent surgery by experienced surgeons associated with the Confederation of American Urology. A retrospective evaluation was designed to review the functional results and the incidence of UO. The technique of orthotopic neobladder construction was at each surgeon's discretion. Various detubularized bowel segments were used, including ileum, colon or sigmoid. Patients were followed by chart reviews and personal interviews at 1, 3 and 6 months after surgery and then every 6 months, and were evaluated by a physical examination, urine analysis, cytology and renal ultrasonography. RESULTS: An ileal or colonic neobladder was constructed in 74 and 64 patients, respectively. Five (7%), 23 (31%), 10 (14%) and 14(9.6%) with an ileal neobladder developed DI, NI, IC and UO, respectively; the respective values for patients with a colonic neobladder were eight (12%), 19 (30%), seven (11%)and 15 (12%). Statistical analysis by Fisher's exact test showed no significant differences between the ileal and colonic neobladder groups or with gender. CONCLUSIONS: Using this specific protocol for evaluating many men and women with ileal and colonic orthotopic neobladders showed no significant differences in the incidence of DI, NI, IC or UO. Neobladders constructed from detubularized bowel, irrespective of bowel segment(s) used, can provide satisfactory diurnal results. A moderate incidence of NI and UO continue to be a problem.

The effect of dietary selenium source and level on the uptake of selenium by developing chick embryos.

We studied the effect of dietary source (organic or inorganic) and level of Se on the Se uptake of chick embryos. After receiving a low-Se diet for 16 wk, 126 Leghorn laying hens were randomly assigned to one of seven dietary treatments. Treatments consisted of feeding a low-Se basal diet alone or with one of three levels of added Se (0.1,0.2, or 0.3 mg/kg Se) supplied by sodium selenite or Se-enriched yeast. Fertile eggs were collected after 33 d of feeding the experimental diets. Eggs were subjected to no incubation or incubation for 5, 10, 15, or 20 d. Non-incubated eggs were separated, and the yolk and albumen were assayed separately for Se. Incubated eggs were separated into the embryo and extra-embryonic portions, which were assayed separately for Se. Se concentrations of the yolk and albumen were significantly different among dietary treatments. Compared with eggs from hens fed sodium selenite, yolk and albumen Se concentrations were higher in eggs from hens fed Se yeast. Embryonic and extra-embryonic Se concentrations were higher in eggs from hens fed Se yeast than eggs from hens fed sodium selenite. The largest increase in embryonic Se concentration was observed during Days 10 to 15 of incubation. It was concluded that Se source and dietary inclusion level influenced the Se concentration of portions of developing embryonated eggs and that embryonic Se concentration changed during incubation.

Predictors of tolerance to chemotherapy in older cancer patients: a prospective pilot study.

Few data are available to help predict which older cancer patient is at risk of developing chemotherapy-related toxicity. This study was a pilot for a project designing a predictive risk score. Chemotherapy patients aged 70 years and older were prospectively enrolled. Chemotherapies were adjusted for their published toxicity. 60 patients were enrolled, 59 were evaluable. Mean dose-intensity was 90.3%, range 33.3-129.0%. 47% of the patients experienced grade 4 haematological and/or grade 3-4 non-haematological toxicity. Published toxicity (MAX2), diastolic blood pressure, marrow invasion and lactate dehydrogenase (LDH) were all associated with toxicity (P<0.1); Body Mass Index, previous chemotherapy, red blood cells, platelets, polymedication with dose-intensity; and polymedication with FACT-G change. After adjustment for the published toxicity, the variables retained their significance, except for LDH and polymedication (for dose-intensity). Although the size of this pilot study imposes a cautious interpretation, patient-related and chemotherapy-related variables correlated independently with toxicity. Designing a composite predictive score to use in assessing the toxicity of multiple chemotherapy regimens therefore appears to be a valid undertaking.

The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects.

The important role that neural tissue fatty acid composition plays in neurodevelopment and various pathological states is increasingly recognized. However, there are limited data regarding the fatty acid composition of normal human brain at various ages. The purpose of this study was to describe human cerebral cortex fatty acid composition from ages 2 to 88 years. The relationship between cerebral cortex and erythrocyte fatty acid composition was also investigated. Samples of frontal cerebral cortex and of erythrocytes were obtained from 58 human subjects on whom autopsies were performed. The mean age of subjects was 40 +/- 29 years, with a range of 2 to 88 years. The fatty acid composition of tissues was determined, and linear regression models were used to describe the relationship between age and the fatty acid composition of cerebral cortex and erythrocytes. The data were bilinear, with changes occurring after the approximate age of 18 years. Therefore, the cohort was divided into subjects with ages < or =18 and >18 years. In the younger group, the polyunsaturated fatty acids generally decreased with age, with the exception of 22:6n3, which demonstrated a significant increase. The level of mono-unsaturated fatty acids, in contrast, generally increased to the age of 18 years. Several of the polyunsaturated fatty acids also decreased with age in the older cohort, particularly 20:4n6. The levels of 18:2n6, however, increased significantly with age in the older cohort. Among subjects < or =18 years of age, there was no significant relationship between cerebral cortex and erythrocyte fatty acid levels. In the older cohort, there was a significant relationship between brain and erythrocyte levels for several fatty acids, particularly 16:0. These data demonstrate that levels of cerebral cortex fatty acids change from early childhood through late adulthood, and indicate that the levels of several erythrocyte fatty acids may be useful in predicting brain fatty acid levels in adults.

Expression of early lung cancer detection marker: hnRNP-A2/B1 and its relation to microsatellite alteration in non-small cell lung cancer.

We have reported that a mouse monoclonal antibody, 703D4, which recognizes heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) can frequently detect lung cancer in exfoliated sputum epithelial cells 1-2 years earlier than routine chest X-ray or sputum cytomorphology. We along with others have shown that microsatellite alteration (MA) at selected loci can be recognized in sputum cells prior to clinical lung cancer. The present study was undertaken to determine how frequently the expression of hnRNP-A2/B1 message is associated with neoplastic clonal expansion as shown by MA in 41 cases of non-small cell lung cancer (NSCLC). We used Northern blotting to evaluate hnRNP-A2/B1 mRNA expression in lung tumor and remote noninvolved lung. We evaluated microsatellite instability (i.e. shifts; MI) or loss of heterozygosity (LOH) with a panel of 13 microsatellite markers at loci identified previously as susceptible in NSCLC. Of the 41 tumors, 25 (61%) over-expressed hnRNP-A2/B1 and 33 (80%) demonstrated MA in at least one of 13 loci (58% in at least two loci). The association between MA (one locus) and the overexpression of hnRNP-A2/B1 is statistically significant (P=0.0082), and those lung tumors with MA at two or more loci were significantly more likely to over-express hnRNP-A2/B1 mRNA (P=0.004). MA of loci on 3p were the only MA statistically associated with hnRNP-A2/B1 message overexpression (P=0.001). We conclude that lung tumor cells undergoing clonal expansion frequently upregulate hnRNP-A2/B1.

Hematopoietic development: a balancing act.

Over the past year, significant new insights have been gained in our understanding of the lineage determination of red blood cells. In particular, evidence has emerged demonstrating that cross-antagonism of lineage-specific transcription factors plays an important role in determining cell phenotype by actively repressing alternate lineage gene programs.

Projecting the standard error of the Kaplan-Meier estimator.

Clinical studies in which a major objective is to produce Kaplan-Meier estimates of survival probabilities should be designed to produce those estimates with a desired prespecified precision as measured by their standard errors. By considering the Peto and Greenwood formulae for the estimated standard error of the Kaplan-Meier estimate and replacing their constituents with expected values based on the study's design parameters, formulae for projected standard errors can be produced. These formulae are shown, through simulations, to be quite accurate.

Importance of lymphatic mapping in ductal carcinoma in situ (DCIS): why map DCIS?

The appropriateness of sentinel lymph node biopsy in the management of patients with biopsy diagnoses of ductal carcinoma in situ (DCIS) or DCIS with microinvasion (DCISM) has not been established. Three hundred forty-one patients presented with a biopsy diagnosis of DCIS or DCISM. Two hundred forty (70%) underwent sentinel node biopsy at their definitive procedure. All clinical and pathologic data were collected prospectively. Of 224 patients with a biopsy diagnosis of DCIS 23 (10%) were upstaged to infiltrating ductal carcinoma (IDC) at their definitive therapy and of 16 patients with a biopsy diagnosis of DCISM seven (44%) were upstaged to IDC. Excisional biopsies were no more sensitive for detecting IDC than was core biopsy. Lymph node metastases were detected in 26 of 195 (13%) patients with a definitive diagnosis of DCIS, in three of 15 (20%) with a definitive diagnosis of DCISM, and in eight of 30 (27%) with a definitive diagnosis of IDC. Sentinel lymph node biopsy is a valuable tool in the treatment of patients with DCIS and DCISM and is particularly needed in those undergoing mastectomy. No "high-risk" group of patients can be identified for selective sentinel lymph node biopsy.