Designing a survey to monitor multi-scale impacts of agri-environment schemes on mobile taxa.

Agri-environment schemes (AES) are key mechanisms to deliver conservation policy, and include management to provide resources for target taxa. Mobile species may move to areas where resources are increased, without this necessarily having an effect across the wider countryside or on populations over time. Most assessments of AES efficacy have been at small spatial scales, over short timescales, and shown varying results. We developed a survey design based on orthogonal gradients of AES management at local and landscape scales, which will enable the response of several taxa to be monitored. An evidence review of management effects on butterflies, birds and pollinating insects provided data to score AES options. Predicted gradients were calculated using AES uptake, weighted by the evidence scores. Predicted AES gradients for each taxon correlated strongly, and with the average gradient across taxa, supporting the co-location of surveys across different taxa. Nine 1 × 1 km survey squares were selected in each of four regional blocks with broadly homogenous background habitat characteristics. Squares in each block covered orthogonal contrasts across the range of AES gradients at local and landscape scales. This allows the effects of AES on species at each scale, and the interaction between scales, to be tested. AES options and broad habitats were mapped in field surveys, to verify predicted gradients which were based on AES option uptake data. The verified AES gradient had a strong positive relationship with the predicted gradient. AES gradients were broadly independent of background habitat within each block, likely allowing AES effects to be distinguished from potential effects of other habitat variables. Surveys of several mobile taxa are ongoing. This design will allow mobile taxa responses to AES to be tested in the surrounding countryside, as well as on land under AES management, and potentially in terms of population change over time. The design developed here provides a novel, pseudo-experimental approach for assessing the response of mobile species to gradients of management at two spatial scales. A similar design process could be applied in other regions that require a standardized approach to monitoring the impacts of management interventions on target taxa at landscape scales, if equivalent spatial data are available.

Morphological and Structural Properties of Amino-Functionalized Fumed Nanosilica and Its Comparison with Nanoparticles Obtained by Modified Stöber Method.

In industry, silica nanoparticles (NPs) are obtained by the fuming and the precipitation method. Fumed silica NPs are commonly used in the preparation of nanocomposites because they have an extremely low bulk density (160-190 kg/m3), large surface area (50-600 m2/g), and nonporous surface, which promotes strong physical contact between the NPs and the organic phase. Fumed silica has fewer silanol groups (Si-OH) on its surface than the silica prepared by the Stöber method. However, the number of -OH groups on the fumed silica surface can be increased by pretreating them with sodium hydroxide (NaOH) before further surface modification. In this study, the effectiveness of the NaOH pretreatment was evaluated on commercial fumed silica NPs with a surface area of 200 m2/g. The number of surface -OH groups was estimated by potentiometric titration. The pretreated fumed NPs, and the precipitated NPs (prepared by the Stöber method) were modified with 3-aminopropyltriethoxysilane (APTES) to obtain A200S and nSiO2-APTES, respectively. The NPs were characterized using electron dispersive scanning (EDS), scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), BET (Brunauer-Emmett-Teller) analysis, and ζ-potential. XRD confirmed the presence of the organo-functional group on the surface of both NPs. After the amino-functionalization, the ζ-potential values of the nSiO2 and A200 changed from -35.5 mV and -14.4 mV to +26.2 mV and +11.76 mV, respectively. Consequently, we have successfully synthesized functionalized NPs with interesting, specific surface area and porosity (pore volume and size), which can be attractive materials for chemical and energy industries.

Key Factors Affecting Reproductive Success of Thoroughbred Mares and Stallions on a Commercial Stud Farm.

To evaluate factors contributing to fertility of thoroughbred mares, data from 3743 oestrous periods of 2385 mares were collected on a large thoroughbred farm in Ireland. Fourteen stallions (mean age 8.3 years; range 4-15 years) had bred 2385 mares (mean age 9.4 years; range 3-24 years). Maiden mares accounted for 12%, mares with a foal at foot for 64%, and barren, slipped or rested mares for 24% of the total. The mean pregnancy rate per cycle was 67.8% (68.6% in year 1 and 66.9% in year 2). Backward stepwise multivariable logistic regression analysis was utilized to develop two models to evaluate mare factors, including mare age, reproductive status, month of foaling, dystocia, month of cover, foal heat, cycle number, treatments, walk-in status and stallion factors including stallion identity, stallion age, shuttle status, time elapsed between covers and high stallion usage on the per cycle pregnancy rate and pregnancy loss. Old age (p < 0.001) and cover within 20 days post-partum (p < 0.003) were associated with lowered pregnancy rates. High mare age (p < 0.05) and barren, slipped or rested reproductive status (p = 0.05) increased the likelihood of pregnancy loss. Uterine inflammation or infection, if appropriately treated, did not affect fertility. Only high usage of stallions (used more than 21 times in previous week) was associated with lowered (p = 0.009) pregnancy rates. However, shuttle stallions were more likely to have increased (p = 0.035) pregnancy survival, perhaps reflecting a bias in stallion selection. In conclusion, mare age exerted the greatest influence on fertility; nonetheless, thoroughbreds can be effectively managed to achieve high reproductive performance in a commercial setting.

Effect of a SILICA/HPAM Nanohybrid on Heavy Oil Recovery and Treatment: Experimental and Simulation Study.

The addition of nanoparticles has been presented as an alternative approach to counteract the degradation of polymeric solutions for enhanced oil recovery. In this context, a nanohybrid (NH34) of partially hydrolyzed polyacrylamide (MW ∼12 MDa) and nanosilica modified with 2% 3-aminopropyltriethoxysilane (nSiO2-APTES) was synthesized and evaluated. NH34 was characterized by using dynamic light scattering, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. Fluid-fluid tests assessed its viscosifying power, mechanical stability, filterability, and emulsion behavior. Rock-fluid tests were carried out to determine the nanohybrid's adsorption in porous media, the inaccessible pore volume (IPV), and the resistance (RF) and residual resistance factors (RRF). These tests were conducted under the conditions of a Colombian field. NH34 results were compared with four (4) commercial polymers (P34, P88, P51, and PA2). The viscosifying power of NH34 was observed to be similar to that of the four commercial polymers at a lower concentration, but it exhibits more resistance to mechanical and chemical degradation. The evaluation of the emulsion behavior showed that the nanohybrid neither changed the dehydration process nor altered the crude oil viscosity, favoring its extraction at the wellhead. However, the water clarification treatment must be adjusted because the oil and grease contents and turbidity increase with the residual concentration of NH34. Incremental oil recovery factors obtained by numerical simulation (compared to waterflooding) were P51 (5.5%) > P34 (4.9%) > P88 (4.8%) > NH34 (2.6%) > PA2 (0.9%). The polymers P51, P34, and P88 had a better recovery factor than NH34 and PA2 due to their lower values of residual adsorption and IPV. Few studies have been reported on polymer nanohybrids' emulsion and flow behavior. Therefore, further research is needed to enhance our understanding of the fundamental enhanced oil recovery mechanisms associated with polymer nanohybrids.

Experimental Investigation of the Viscosity and Stability of Scleroglucan-Based Nanofluids for Enhanced Oil Recovery.

Biopolymers emerge as promising candidates for enhanced oil recovery (EOR) applications due to their molecular structures, which exhibit better stability than polyacrylamides under harsh conditions. Nonetheless, biopolymers are susceptible to oxidation and biological degradation. Biopolymers reinforced with nanoparticles could be a potential solution to the issue. The nanofluids' stability and performance depend on the nanoparticles' properties and the preparation method. The primary objective of this study was to evaluate the effect of the preparation method and the nanoparticle type (SiO2, Al2O3, and TiO2) on the viscosity and stability of the scleroglucan (SG). The thickening effect of the SG solution was improved by adding all NPs due to the formation of three-dimensional structures between the NPs and the SG chains. The stability test showed that the SG + Al2O3 and SG + TiO2 nanofluids are highly unstable, but the SG + SiO2 nanofluids are highly stable (regardless of the preparation method). According to the ANOVA results, the preparation method and standing time influence the nanofluid viscosity with a statistical significance of 95%. On the contrary, the heating temperature and NP type are insignificant. Finally, the nanofluid with the best performance was 1000 ppm of SG + 100 ppm of SiO2_120 NPs prepared by method II.

Flow Behavior through Porous Media and Displacement Performance of a SILICA/PAM Nanohybrid: Experimental and Numerical Simulation Study.

Nanoparticles (NPs) have been proposed as additives to improve the rheological properties of polymer solutions and reduce mechanical degradation. This study presents the results of the retention experiment and the numerical simulation of the displacement efficiency of a SiO2/hydrolyzed polyacrylamide (HPAM) nanohybrid (CSNH-AC). The CSNH-AC was obtained from SiO2 NPs (synthesized by the Stöber method) chemically modified with HPAM chains. Attenuated total reflection-Fourier transform infrared spectroscopy, field emission gun-scanning electron microscopy, X-ray diffraction, and thermogravimetric analysis were used to characterize the nanohybrid. The injectivity and dynamic retention tests were performed at 56 °C in a sandstone core with a porosity of ∼26% and a permeability of 117 and 287 mD. A history matching of the dynamic retention test was performed to determine the maximum and residual adsorption, IPV, and residual resistance factor (RRF). A laboratory-scale model was used to evaluate the displacement efficiency of CSNH-AC and HPAM through numerical simulation. According to the results, the nanohybrid exhibits better rheological behavior than the HPAM solution at a lower concentration. The nanopolymer sol adsorption and IPV (29,7 µg/grock, 14,5) are greater than those of the HPAM solution (9,2 µg/grock, 10), which was attributed to the difference between the rock permeabilities used in the laboratory tests (HPAM: 287 mD and CSNH-AC: 117 mD). The RF of both samples gradually increases with the increase in shear rate, while the RRF slightly decreases and tends to balance. However, the nanopolymer sol exhibits greater RF and RRF values than that of the polymer solution due to the strong flow resistance of the nanohybrid (higher retention in the porous media). According to the field-scale simulation, the incremental oil production could be 295,505 and 174,465 barrels for the nanopolymer sol and the HPAM solution, respectively (compared to waterflooding). This will represent an incremental recovery factor of 11.3% for the nanopolymer sol and 6.7% for the HPAM solution.

C-terminal amino acid residues of the trimeric autotransporter adhesin YadA of Yersinia enterocolitica are decisive for its recognition and assembly by BamA.

The Bam complex is a highly conserved multiprotein machine essential for the assembly of ß-barrel outer membrane proteins. It is composed of the essential outer membrane protein BamA and four outer membrane associated lipoproteins BamB-E. The Yersinia enterocolitica Adhesin A (YadA) is the prototype of trimeric auotransporter adhesins (TAAs), consisting of a head, stalk and a ß-barrel membrane anchor. To investigate the role of BamA in biogenesis of TAAs, we expressed YadA in a BamA-depleted strain of Escherichia coli, which resulted in degradation of YadA. Yeast-two-hybrid experiments and immunofluorescence studies revealed that BamA and YadA interact directly and colocalize. As BamA recognizes the C-terminus of OMPs, we exchanged the nine most C-terminal amino acids of YadA. Substitution of the amino acids in position 1, 3 or 5 from the C-terminus with glycine resulted in DegP-dependent degradation of YadA. Despite degradation all YadA proteins assembled in the outer membrane. In summary we demonstrate that (i) BamA is essential for biogenesis of the TAA YadA, (ii) BamA interacts directly with YadA, (iii) the C-terminal amino acid motif of YadA is important for the BamA-dependent assembly and differs slightly compared with other OMPs, and (iv) BamA and YadA colocalize.

Can we abandon anthracyclines for early breast cancer patients?

Anthracycline-containing regimens improve disease-free and overall survival of patients with early breast cancer, but the toxicity, especially the cardiotoxicity, of the anthracyclines make them unattractive in the adjuvant setting. Two large, randomized trials, one in unselected patients and one in those with HER2-positive tumors, suggest that a taxane combination without an anthracycline might be just as effective as more traditional regimens. These and other studies also suggest that the anthracyclines might reasonably be used only for those with more aggressive forms of breast cancer, as defined by molecular markers. The results of these studies are provocative but insufficient to justify the conclusion that anthracyclines can be either abandoned or used only for a very select group of patients.

Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial.

BACKGROUND: Tamoxifen is standard adjuvant treatment for postmenopausal women with hormone-receptor-positive breast cancer. We assessed the benefit of adding chemotherapy to adjuvant tamoxifen and whether tamoxifen should be given concurrently or after chemotherapy. METHODS: We undertook a phase 3, parallel, randomised trial (SWOG-8814, INT-0100) in postmenopausal women with hormone-receptor-positive, node-positive breast cancer to test two major objectives: whether the primary outcome, disease-free survival, was longer with cyclophosphamide, doxorubicin, and fluorouracil (CAF) given every 4 weeks for six cycles plus 5 years of daily tamoxifen than with tamoxifen alone; and whether disease-free survival was longer with CAF followed by tamoxifen (CAF-T) than with CAF plus concurrent tamoxifen (CAFT). Overall survival and toxicity were predefined, important secondary outcomes for each objective. Patients in this open-label trial were randomly assigned by a computer algorithm in a 2:3:3 ratio (tamoxifen:CAF-T:CAFT) and analysis was by intention to treat of eligible patients. Groups were compared by stratified log-rank tests, followed by Cox regression analyses adjusted for significant prognostic factors. This trial is registered with ClinicalTrials.gov, number NCT00929591. FINDINGS: Of 1558 randomised women, 1477 (95%) were eligible for inclusion in the analysis. After a maximum of 13 years of follow-up (median 8.94 years), 637 women had a disease-free survival event (tamoxifen, 179 events in 361 patients; CAF-T, 216 events in 566 patients; CAFT, 242 events in 550 patients). For the first objective, therapy with the CAF plus tamoxifen groups combined (CAFT or CAF-T) was superior to tamoxifen alone for the primary endpoint of disease-free survival (adjusted Cox regression hazard ratio [HR] 0.76, 95% CI 0.64-0.91; p=0.002) but only marginally for the secondary endpoint of overall survival (HR 0.83, 0.68-1.01; p=0.057). For the second objective, the adjusted HRs favoured CAF-T over CAFT but did not reach significance for disease-free survival (HR 0.84, 0.70-1.01; p=0.061) or overall survival (HR 0.90, 0.73-1.10; p=0.30). Neutropenia, stomatitis, thromboembolism, congestive heart failure, and leukaemia were more frequent in the combined CAF plus tamoxifen groups than in the tamoxifen-alone group. INTERPRETATION: Chemotherapy with CAF plus tamoxifen given sequentially is more effective adjuvant therapy for postmenopausal patients with endocrine-responsive, node-positive breast cancer than is tamoxifen alone. However, it might be possible to identify some subgroups that do not benefit from anthracycline-based chemotherapy despite positive nodes. FUNDING: National Cancer Institute (US National Institutes of Health).

HER2 and response to paclitaxel in node-positive breast cancer.

BACKGROUND: The status of human epidermal growth factor receptor type 2 (HER2) in breast-cancer cells predicts clinical outcomes in women who receive adjuvant anthracycline-based chemotherapy. We hypothesized that HER2 positivity predicts a benefit from adjuvant doxorubicin doses above standard levels, from the addition of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide, or from both. METHODS: We randomly selected 1500 women from 3121 women with node-positive breast cancer who had been randomly assigned to receive doxorubicin (60, 75, or 90 mg per square meter of body-surface area) plus cyclophosphamide (600 mg per square meter) for four cycles, followed by four cycles of paclitaxel (175 mg per square meter) or observation. Tissue blocks from 1322 of these 1500 women were available. Immunohistochemical analyses of these tissue specimens for HER2 with the CB11 monoclonal antibody against HER2 or with a polyclonal-antibody assay kit and fluorescence in situ hybridization for HER2 amplification were performed. RESULTS: No interaction was observed between HER2 positivity and doxorubicin doses above 60 mg per square meter. HER2 positivity was, however, associated with a significant benefit from paclitaxel. The interaction between HER2 positivity and the addition of paclitaxel to the treatment was associated with a hazard ratio for recurrence of 0.59 (P=0.01). Patients with a HER2-positive breast cancer benefited from paclitaxel, regardless of estrogen-receptor status, but paclitaxel did not benefit patients with HER2-negative, estrogen-receptor-positive cancers. CONCLUSIONS: The expression or amplification, or both, of HER2 by a breast cancer is associated with a benefit from the addition of paclitaxel after adjuvant treatment with doxorubicin (<60 mg per square meter) plus cyclophosphamide in node-positive breast cancer, regardless of estrogen-receptor status. Patients with HER2-negative, estrogen-receptor-positive, node-positive breast cancer may gain little benefit from the administration of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide.

New Nanohybrid Based on Hydrolyzed Polyacrylamide and Silica Nanoparticles: Morphological, Structural and Thermal Properties.

In this study, a set of advanced characterization techniques were used to evaluate the morphological, structural, and thermal properties of a novel molecular hybrid based on silica nanoparticles/hydrolyzed polyacrylamide (CSNH-PC1), which was efficiently obtained using a two-step synthetic pathway. The morphology of the nanohybrid CSNH-PC1 was determined using scanning electron microscopy (SEM), dynamic light scattering (DLS), and nanotracking analysis (NTA) techniques. The presence of C, N, O, and Si atoms in the nanohybrid structure was verified using electron dispersive scanning (EDS). Moreover, the corresponding structural analysis was complemented using powder X-ray diffraction (XRD) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR). The covalent bond between APTES-functionalized SiO2 nanoparticles (nSiO2-APTES), and the hydrolyzed polyacrylamide (HPAM) chain (MW ≈ 20.106 Da) was confirmed with high-resolution X-ray spectroscopy (XPS). Finally, the thermal properties of the nanohybrid were evaluated by using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The results showed that the CSNH-PC1 has a spherical morphology, with sizes between 420-480 nm and higher thermal resistance compared to HPAM polymers without modification, with a glass transition temperature of 360 °C. The integration of these advanced characterization techniques implemented here shows promising results for the study and evaluation of new nanomaterials with multiple applications.

Fifteen-year median follow-up results after neoadjuvant doxorubicin, followed by mastectomy, followed by adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) followed by radiation for stage III breast cancer: a phase II trial (CALGB 8944).

PURPOSE: To describe long-term results of a multimodality strategy for stage III breast cancer utilizing neoadjuvant doxorubicin followed by mastectomy, CMF, and radiotherapy. PATIENTS AND METHODS: Women with biopsy-proven, clinical stage III breast cancer and adequate organ function were eligible. Neoadjuvant doxorubicin (30 mg/m(2) days 1-3, every 28 days for 4 cycles) was followed by mastectomy, in stable or responding patients. Sixteen weeks of postoperative CMF followed (continuous oral cyclophosphamide (2 mg/kg/day); methotrexate (0.7 mg/kg IV) and fluorouracil (12 mg/kg IV) weekly, weeks 1-8, and than biweekly, weeks 9-16). Radiation therapy followed adjuvant chemotherapy. RESULTS: Clinical response rate was 71% (79/111, 95% CI = 62-79%), with 19% complete clinical response. Pathologic complete response was 5% (95% CI = 2-11%). Median follow-up is 15.6 years. Half of the patients progressed by 2.2 years; half died by 5.4 years (range 6 months-15 years). The hazard of dying was greatest in the first 5 years after diagnosis and declined thereafter. Time to progression and overall survival were predicted by number of pathologically involved lymph nodes (TTP: HR [10 vs. 1 node] 2.40, 95% CI = 1.63-3.53, P < 0.0001; OS: HR 2.50, 95% CI = 1.74-3.58, P < 0.0001). CONCLUSIONS: After multimodality treatment for locally advanced breast cancer, long-term survival was correlated with the number of pathologically positive lymph nodes, but not to clinical response. The hazard of death was highest during the first 5 years after diagnosis and declined thereafter, indicating a possible intermediate endpoint for future trials of neoadjuvant treatment.

Dose-escalation of filgrastim does not improve efficacy: clinical tolerability and long-term follow-up on CALGB study 9141 adjuvant chemotherapy for node-positive breast cancer patients using dose-intensified doxorubicin plus cyclophosphamide followed by paclitaxel.

PURPOSE: To assess the safety, tolerability, and clinical outcomes of an adjuvant chemotherapy regimen designed to incorporate a non-cross-resistant agent (paclitaxel, T) with a maximally dose-intensified regimen of doxorubicin and cyclophosphamide (AC) in conjunction with hematopoietic growth factor support (recombinant human granulocyte-colony stimulating factor; G-CSF; Filgrastim). A secondary aim was to assess if a higher dose (10 mcg/kg/day) of G-CSF is more efficacious than the conventional dose (5 mcg/kg/day) in this setting. PATIENTS AND METHODS: Female patients with early-stage, node-positive invasive breast cancer were eligible for this multicenter, cooperative group feasibility trial that was designed as the pilot study for a larger randomized clinical trial. The protocol treatment comprised five cycles of dose-intensified AC (75 and 2000 mg/m(2)/cycle, respectively, intravenously every three weeks) with G-CSF support, followed by an additional four cycles of T (175 mg/m(2) by 3h intravenous infusion, every three weeks). Patients were randomized to receive one of two dose levels of G-CSF (5 vs. 10 mcg/kg/day) during AC chemotherapy. Data on both short-term toxicity and long-term survival were collected. RESULTS: One hundred and seventy two node-positive patients with operable primary breast cancer were accrued to this trial between February 1993 and April 1994. 130 of the 172 patients (76%) completed all protocol-specified therapy. Of the 42 early study withdrawals, 23 were due to unacceptable acute treatment-related toxicity. No differences in toxicities or clinical outcomes were noted between the two different dose levels of G-CSF support. At 6.8 years median follow-up, relapse-free survival (RFS) and overall survival (OS) rates for all patients are 70% and 78%, respectively. Ten patients developed second malignancies during follow-up, including three cases with a hematologic malignancy (2% incidence). CONCLUSION: The delivery of dose-intensified AC followed by T was feasible in this large-scale pilot trial, although significant acute toxicities were commonly encountered. The data confirmed the acceptable tolerability of T after aggressive myelotoxic therapy in the adjuvant setting, leading to a larger randomized clinical trial comparing three dose levels of doxorubicin in AC with or without the addition of T (CALGB 9344). Supportive care using twice the conventional dose of G-CSF did not significantly improve the tolerability or change the toxicities of this regimen, and the occurrence of secondary malignancies is consistent with the emerging risk profile of dose-intensive regimens with growth factor support. With long-term follow-up, the clinical outcomes remain relatively favorable and correlate with such expected prognostic factors as the number of involved nodes and hormone receptor status.

Pharmacodynamic markers of perifosine efficacy.

PURPOSE: It is critical to develop methods to quantify the early pharmacodynamic effects of targeted therapeutics in vivo to make drug development more efficient and ensure biologically relevant dosing. Furthermore, an ability to identify patients likely to respond to targeted therapeutics would decrease the size, duration, and cost of clinical trials, resulting in more efficient translation to improved patient outcomes. Recent studies suggest that perifosine inhibits the phosphatidylinositol-3'-kinase (PI3K) pathway by preventing cell membrane recruitment of the AKT pleckstrin homology domain. EXPERIMENTAL DESIGN: A novel functional proteomics technology, reverse phase protein array, was used to establish and quantify pharmacodynamic markers of perifosine efficacy. RESULTS: Perifosine selectively prevents AKT recruitment to the membrane and blocks activation of downstream effectors. Perifosine inhibited breast, ovarian, and prostate cancer models. Growth inhibition was associated with apoptosis. Activation of AKT as a consequence of genomic aberrations predicted perifosine efficacy. In cell lines and xenografts, there was a highly statistically significant correlation between the degree of antitumor efficacy of different perifosine doses and quantified down-regulation of phosphorylation of AKT and of its downstream targets, particularly S6. CONCLUSIONS: Because of a strong correlation between proportional modulation of PI3K pathway biomarkers and quantified perifosine efficacy, it is likely that early measurement of such pharmacodynamic biomarkers with reverse phase protein array will optimize selection of responding patients and guide perifosine dosing. Furthermore, PI3K pathway activation status may allow baseline selection of patients most likely to respond to perifosine alone or in combination with other therapies.

Lymphoproliferative disease with features of lymphoma in the central nervous system of a horse.

Lymphoma (malignant lymphoma, lymphosarcoma) is uncommon in horses in the United Kingdom. This report describes an unusual form of lymphoproliferative disease with features of lymphoma restricted to the central nervous system (CNS) and with no evidence of a primary lesion elsewhere. Immunohistochemical examination defined an overwhelming predominance of T lymphocytes with admixed B lymphocytes and activated macrophages. This case exemplifies the challenges associated with definitive diagnosis of lymphoproliferative disease of the equine CNS.

Study of the short- and long-term outcomes of 65 horses with peritonitis.

The records of 65 horses with peritonitis examined at two UK referral centres over a period of 12 years were reviewed. Peritonitis was defined in terms of the horse's peritoneal fluid containing more than 5 x 10(9) nucleated cells/l. Horses that had developed peritonitis after abdominal surgery or a rupture of the gastrointestinal tract were excluded. Of the 65 horses, 56 (86 per cent) survived to be discharged. Follow-up information was obtained from practice records and telephone calls to the owners for 38 of the horses. Of these, 32 (84 per cent) had survived for at least 12 months and were considered to be long-term survivors; the others six were euthanased within 12 months. Thirteen (34 per cent) of the horses discharged had experienced complications that could have been sequelae to peritonitis and eight of the 13 were euthanased. The cause of the peritonitis was identified in 15 cases; survival rates were lowest in horses with peritonitis secondary to urinary tract involvement or intra-abdominal masses. Of the other 50 cases, 47 (94 per cent) survived to discharge, but two were euthanased owing to recurrent colic.

CD103+CD11b+ mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin.

Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103+CD11b+ (DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+CD11b- (SP) are not required for these responses. The lack of this response correlated with a complete absence of sFliC-specific plasma cells in the MLN, small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice expressed α4ß7+, suggesting a mucosal origin. Collectively, these results suggest that mucosal DP cDC contribute to the generation of the sFliC-specific plasma cell pool in the BM and thus serve as a bridge linking the mucosal and systemic immune system.

Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer.

BACKGROUND: In women 70 years of age or older who have early breast cancer, it is unclear whether lumpectomy plus tamoxifen is as effective as lumpectomy followed by tamoxifen plus radiation therapy. METHODS: Between July 1994 and February 1999, we randomly assigned 636 women who were 70 years of age or older and who had clinical stage I (T1N0M0 according to the tumor-node-metastasis classification), estrogen-receptor-positive breast carcinoma treated by lumpectomy to receive tamoxifen plus radiation therapy (317 women) or tamoxifen alone (319 women). Primary end points were the time to local or regional recurrence, the frequency of mastectomy for recurrence, breast-cancer-specific survival, the time to distant metastasis, and overall survival. RESULTS: The only significant difference between the two groups was in the rate of local or regional recurrence at five years (1 percent in the group given tamoxifen plus irradiation and 4 percent in the group given tamoxifen alone, P<0.001). There were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence, distant metastases, or five-year rates of overall survival (87 percent in the group given tamoxifen plus irradiation and 86 percent in the tamoxifen group, P=0.94). Assessment by physicians and patients of cosmetic results and adverse events uniformly rated tamoxifen plus irradiation inferior to tamoxifen alone. CONCLUSIONS: Lumpectomy plus adjuvant therapy with tamoxifen alone is a realistic choice for the treatment of women 70 years of age or older who have early, estrogen-receptor-positive breast cancer.