Pathological responses and survival outcomes in patients with locally advanced breast cancer after neoadjuvant chemotherapy: a single-institute experience.

BACKGROUND: Pathological complete response (pCR) is a surrogate for the efficacy of neoadjuvant chemotherapy (NCT) in locally advanced breast cancer (LABC). We analyzed the predictive clinical factors for pathological responses and survival outcomes in a cohort of Egyptian patients. METHODS: We evaluated the medical records of patients with breast cancer who received NCT in our academic institute. Survival curves were estimated with the Kaplan-Meier method. Cox proportional models were used for multiple regression analysis. RESULTS: Our cohort included 368 patients with a median age of 48 years (range 21-70). The median follow-up time was 3 years. The clinical tumor stage (T3-4) represented 58%, with 80% having positive axillary nodes. The luminal subgroup prevailed by 68%. The objective response rate (ORR) reached 78%, and 16% of patients achieved pCR. The clinical node stage and optimal chemotherapy were associated with higher ORR (p = 0.035 and p = 0.001, respectively). Predictors of pCR were clinical T-stage (p = 0.026), high Ki-67 index > 20 (p = 0.05), and receiving optimal chemotherapy (p = 0.014). The estimated 3-year disease free-survival (DFS) was 53%. Receptor status, achieving ORR, and pCR were associated with better DFS with hazard ratios of 0.56, p = 0.008; 0.38, p = 0.04; and 0.28, p = 0.007, respectively. CONCLUSIONS: Luminal tumors still draw benefit from neoadjuvant chemotherapy in terms of clinical response and breast conservative surgery. Treatment escalation to those who did not achieve pCR requires more investigation, given a higher recurrence rate in real-world experience.

Genomic Prediction of Yield Traits in Single-Cross Hybrid Rice (Oryza sativa L.).

Hybrid rice varieties can outyield the best inbred varieties by 15 - 30% with appropriate management. However, hybrid rice requires more inputs and management than inbred rice to realize a yield advantage in high-yielding environments. The development of stress-tolerant hybrid rice with lowered input requirements could increase hybrid rice yield relative to production costs. We used genomic prediction to evaluate the combining abilities of 564 stress-tolerant lines used to develop Green Super Rice with 13 male sterile lines of the International Rice Research Institute for yield-related traits. We also evaluated the performance of their F1 hybrids. We identified male sterile lines with good combining ability as well as F1 hybrids with potential further use in product development. For yield per plant, accuracies of genomic predictions of hybrid genetic values ranged from 0.490 to 0.822 in cross-validation if neither parent or up to both parents were included in the training set, and both general and specific combining abilities were modeled. The accuracy of phenotypic selection for hybrid yield per plant was 0.682. The accuracy of genomic predictions of male GCA for yield per plant was 0.241, while the accuracy of phenotypic selection was 0.562. At the observed accuracies, genomic prediction of hybrid genetic value could allow improved identification of high-performing single crosses. In a reciprocal recurrent genomic selection program with an accelerated breeding cycle, observed male GCA genomic prediction accuracies would lead to similar rates of genetic gain as phenotypic selection. It is likely that prediction accuracies of male GCA could be improved further by targeted expansion of the training set. Additionally, we tested the correlation of parental genetic distance with mid-parent heterosis in the phenotyped hybrids. We found the average mid-parent heterosis for yield per plant to be consistent with existing literature values at 32.0%. In the overall population of study, parental genetic distance was significantly negatively correlated with mid-parent heterosis for yield per plant (r = -0.131) and potential yield (r = -0.092), but within female families the correlations were non-significant and near zero. As such, positive parental genetic distance was not reliably associated with positive mid-parent heterosis.

Combined analysis of modeled and monitored SO2 concentrations at a complex smelting facility.

UNLABELLED: Vale Canada Limited owns and operates a large nickel smelting facility located in Sudbury, Ontario. This is a complex facility with many sources of SO2 emissions, including a mix of source types ranging from passive building roof vents to North America's tallest stack. In addition, as this facility performs batch operations, there is significant variability in the emission rates depending on the operations that are occurring. Although SO2 emission rates for many of the sources have been measured by source testing, the reliability of these emission rates has not been tested from a dispersion modeling perspective. This facility is a significant source of SO2 in the local region, making it critical that when modeling the emissions from this facility for regulatory or other purposes, that the resulting concentrations are representative of what would actually be measured or otherwise observed. To assess the accuracy of the modeling, a detailed analysis of modeled and monitored data for SO2 at the facility was performed. A mobile SO2 monitor sampled at five locations downwind of different source groups for different wind directions resulting in a total of 168 hr of valid data that could be used for the modeled to monitored results comparison. The facility was modeled in AERMOD (American Meteorological Society/U.S. Environmental Protection Agency Regulatory Model) using site-specific meteorological data such that the modeled periods coincided with the same times as the monitored events. In addition, great effort was invested into estimating the actual SO2 emission rates that would likely be occurring during each of the monitoring events. SO2 concentrations were modeled for receptors around each monitoring location so that the modeled data could be directly compared with the monitored data. The modeled and monitored concentrations were compared and showed that there were no systematic biases in the modeled concentrations. IMPLICATIONS: This paper is a case study of a Combined Analysis of Modelled and Monitored Data (CAMM), which is an approach promulgated within air quality regulations in the Province of Ontario, Canada. Although combining dispersion models and monitoring data to estimate or refine estimates of source emission rates is not a new technique, this study shows how, with a high degree of rigor in the design of the monitoring and filtering of the data, it can be applied to a large industrial facility, with a variety of emission sources. The comparison of modeled and monitored SO2 concentrations in this case study also provides an illustration of the AERMOD model performance for a large industrial complex with many sources, at short time scales in comparison with monitored data. Overall, this analysis demonstrated that the AERMOD model performed well.

Detection of bacteria from biological mixtures using immunomagnetic separation combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

A rapid method for identifying specific bacteria from complex biological mixtures using immunomagnetic separation coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has been developed. The technique employs commercially available magnetic beads coated with polycolonal antibodies raised against specific bacteria and whole cell analysis by MALDI-MS. A suspension of a bacterial mixture is mixed with the immunomagnetic beads specific for the target microorganism. After a short incubation period (20 mins) the bacteria captured by the beads are washed, resuspended in deionized H(2)O and directly applied onto a MALDI probe. Liquid suspensions containing bacterial mixtures can be screened within 1 h total analysis time. Positive tests result in the production of a fingerprint mass spectrum primarily consisting of protein biomarkers characteristic of the targeted microorganism. Using this procedure, Salmonella choleraesuis was isolated and detected from standard bacterial mixtures and spiked samples of river water, human urine, and chicken blood.

On-probe sample pretreatment for the detection of proteins above 15 KDa from whole cell bacteria by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

A rapid methodology is described for the enhancement of the signal-to-base-line (S/B) ratio of high molecular weight protein signals from whole cell bacteria analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). The procedure involves depositing growing bacteria colonies from culture dishes directly onto the MALDI probe followed by treatment of the sample spot with a 2 microL aliquot of 40% ethanol prior to the addition of a ferulic acid matrix solution (12.5 mg dissolved in 17% formic acid/33% acetonitrile/50% H(2)O). Protein signals of more than 20 kDa were routinely produced from both Gram positive and Gram negative bacteria prepared in this manner. Moreover, a substantial number of intense protein signals were also produced in the more 'conventional' fingerprint region extending from 4 to 20 kDa. This approach is rapid, easy to implement into existing methodologies, and does not require any special hardware.

Investigation of cell culture media infected with viruses by pyrolysis mass spectrometry: implications for bioaerosol detection.

Mass spectrometry coupled with a pyrolysis inlet system was used to investigate media from cell cultures infected with viruses. Cell culture media is an intricate mixture of numerous chemical constituents and cells that collectively produce complicated mass spectra. Cholesterol and free fatty acids were identified and attributed to lipid sources in the media (blood serum supplement and plasma membranes of host cells). These lipid moieties could be utilized as signature markers for rapidly detecting the cell culture media. Viruses are intracellular parasites and are dependent upon host cells in order to exist. Therefore, it is highly probable that significant quantities of media needed to grow and maintain viable host cells would be present if a viral agent were disseminated as an aerosol into the environment. Cholesterol was also detected from a purified virus sample, further substantiating its use as a target compound for detection. Implications of this research for detection of viral bioaerosols, using a field-portable pyrolysis mass spectrometer, is described.

A population-based clinical trial with the SPf66 synthetic Plasmodium falciparum malaria vaccine in Venezuela.

A phase III malaria vaccine trial in 13 villages in an endemic area, South Venezuela, compared incidence rates of Plasmodium falciparum and Plasmodium vivax infections in 1422 vaccinated and 938 nonvaccinated subjects over 18 months. The SPf66 vaccine was given in three doses, on days 0, 20, and 112. Vaccination was complete in 976 subjects (68.7%). Minor side effects requiring no treatment were reported by 123 (12.6%), with an apparent increase in frequency from the first to the third vaccine dose. No autoimmune evidence was observed in a sample of subjects. Antibodies against SPf66 were present at low titers in 24.7% of tested subjects before vaccination, increasing to 53.6% after the second dose and to 73.6% after the third dose; 26.4% of subjects initially seronegative never seroconverted. The SPf66 malaria vaccine showed a protective efficacy of 55% (95% confidence interval, 21%-75%) against P. falciparum and of 41% (19%-57%) against P. vivax malaria.

[Kaposi angiosarcoma in renal transplant recipients]. / L'angiosarcome de Kaposi chez les transplantés rénaux.

Four cases of Kaposi's sarcoma in recipients of renal transplants are reported. The 4 patients of Italian origin were male. Kaposi's sarcoma, began during pre-transplantation haemodialysis, then extended in one of the patients; in the remaining 3 patients it developed 20 months on average after transplantation. All patients were receiving an immunosuppressive treatment (azathioprine, systemic corticosteroids, anti-lymphocyte serum). Kaposi's sarcoma was located in the skin and mucosae, sometimes in lymph nodes and viscera. In 2 patients the cutaneous and mucosal lesions responded well to vindesine: in the other two patients withdrawal of the immunosuppressive therapy had no effect on the course of the disease. This study highlights the multiple factors involved in the development of Kaposi's sarcoma, notably immunosuppression and the ethnic factor.