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Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with beneficial long-term outcome in early breast cancer (EBC). pCR is defined as ypT0/is, ypN0. It is well known that pCR rates depend on tumor subtype. However, the impact of different therapy regimens, dose delays and dose reductions on pCR rates is still unclear. This retrospective study analyzed the therapy dose of patients with pCR and non-pCR after NACT for EBC using referenced and delivered summation dose intensity product (SDIP) and relative dose intensity (RDI) calculations. Methods: SDIP of different therapy regimens were calculated by defining a unit dose intensity (UDI) for each therapy (Hryniuk et al. JCO 1998). The UDI is defined as the dose in mg/m2/week that produces a 30% complete or partial remission rate as a single agent in first-line therapy for metastatic breast cancer. For each regimen, the planned dose intensities (PDI) were divided by the UDI for every single drug. The summation dose intensity (SDI) is the addition of the resulting decimal fractions. Multiplying the SDI by the treatment intervals and number of cycles gives the SDIP. SDIP can be divided into referenced SDIP (rSDIP) and delivered SDIP (dSDIP). RDI is the ratio of dSDIP in comparison to rSDIP. Therapy dose calculations were performed for patients who received NACT for EBC at the National Center for Tumor Diseases (NCT) Heidelberg, Germany, between 01/2015 and 08/2019. Results: 590 patients (median age 51 years) were included, median follow up was 38 months, 225 patients (38.1%) achieved pCR. 65 patients (11.0%) were hormone receptor positive HER2 negative (HR+HER2-), 164 (27.8%) were HR-HER2-, 133 (22.5%) were HR+HER2+, 97 (16.4%) were HR-HER2+. Significant difference between the pCR and non-pCR group was observed for HR-status (p Citation Format: Thomas M Deutsch, Michelle Kobel, Manuel Feisst, Fabian Riedel, Katharina Smetanay, Carlo Fremd, Laura Michel, Michael Golatta, Joerg Heil, Markus Wallwiener, Andreas Schneeweiss. Impact of summation dose intensity product on pathologic response in patients receiving neoadjuvant chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-08.

IntroductionStereotactic radiosurgery is a well-established treatment option in the management of brain metastases. Multiple prognostic scores for prediction of survival following radiotherapy exist, but are not disease-specific or validated for radiosurgery in women with primary pelvic gynecologic malignancies metastatic to the brain. The aim of the present study is to evaluate the feasibility, safety, outcomes, and impact of established prognostic scores.MethodsWe retrospectively identified 52 patients treated with radiotherapy for brain metastases between 2008 and 2021. Stereotactic radiosurgery was utilized in 31 patients for an overall number of 75 lesions; the remaining 21 patients received whole-brain radiotherapy. Kaplan-Meier survival analysis and the log-rank test were used to calculate and compare survival curves and univariate and multivariate Cox regression to assess the influence of cofactors on recurrence, local control, and prognosis.ResultsWith a median follow-up of 10.7 months, overall survival rates post radiosurgery were 65.3%, 51.3%, and 27.7% for 1, 2, and 5 years, respectively, which were significantly higher than post whole-brain radiotherapy (p=0.049). Five local failures (6.7%) were detected, resulting in 1 and 2 year local cerebral control rates of 97.4% and 94.0%, respectively. Univariate factors for prediction of superior overall survival were high performance status (p=0.030) and application of three prognostic scores, especially the Recursive Partitioning Analysis score (p=0.028). Uni- and multivariate analysis revealed that extracranial progression prior to radiosurgery was significant for inferior overall survival (pConclusionStereotactic radiosurgery for brain metastases from pelvic gynecologic malignancies appears to be safe and well tolerated, achieving promising local cerebral control. Prognostic scores were shown to be transferable and radiosurgery should be recommended as primary intracranial treatment, especially in women with no prior extracranial progression and Recursive Partitioning Analysis class I.

Summary Background The development of anti-HER2 antibody–drug conjugates opens new therapeutic options for patients with breast cancer, including patients with low expression of HER2. To characterise this new breast cancer subtype, we have compared the clinical and molecular characteristics of HER2-low-positive and HER2-zero breast cancer, including response to neoadjuvant chemotherapy and prognosis. Methods In this pooled analysis of individual patient data, we evaluated a cohort of 2310 patients with HER2-non-amplified primary breast cancer that were treated with neoadjuvant combination chemotherapy in four prospective neoadjuvant clinical trials (GeparSepto, NCT01583426 ; GeparOcto, NCT02125344 ; GeparX, NCT02682693 ; Gain-2 neoadjuvant, NCT01690702 ) between July 30, 2012, and March 20, 2019. Central HER2 testing was done prospectively before random assignment of participants in all trials. HER2-low-positive status was defined as immunohistochemistry (IHC) 1+ or IHC2+/in-situ hybridisation negative and HER2-zero was defined as IHC0, based on the American Society of Clinical Oncology/College of American Pathologists guidelines. Disease-free survival and overall survival data were available for 1694 patients (from all trials except GeparX) with a median follow-up of 46·6 months (IQR 35·0–52·3). Bivariable and multivariable logistic regression models and Cox-proportional hazards models were performed based on a predefined statistical analysis plan for analysis of the endpoints pathological complete response, disease-free survival, and overall survival. Findings A total of 1098 (47·5%) of 2310 tumours were HER2-low-positive and 1212 (52·5%) were HER2-zero. 703 (64·0%) of 1098 patients with HER2-low-positive tumours were hormone receptor positive, compared with 445 (36·7%) of 1212 patients with HER2-zero tumours (p Interpretation Our results show that HER2-low-positive tumours can be identified as new subgroup of breast cancer by standardised IHC, distinct from HER2-zero tumours. HER2-low-positive tumours have a specific biology and show differences in response to therapy and prognosis, which is particularly relevant in therapy-resistant, hormone receptor-negative tumours. Our results provide a basis for a better understanding of the biology of breast cancer subtypes and the refinement of future diagnostic and therapeutic strategies. Funding German Cancer Aid (Deutsche Krebshilfe).

Este artículo analiza la importancia de la teoría crítica de la enseñanza para el aprendizaje significativo de la tributación, con el fin de potenciar a los contadores públicos a partir de la formación basada en la autorreflexión, valoración crítica y desarrollo de competencias para la discusión y comprensión del objeto de estudio del área de tributaria. Se trabajó con un enfoque cualitativo y se requirió un criterio metodológico hermenéutico-dialéctico; por medio de un análisis compartido con docentes y estudiantes de programas de contaduría pública de universidades del departamento del Quindío, para generar un diálogo sobre el estado del área de tributaria impartida en los currículos que permitiera una interpretación, categorización y comprensión crítica. Además, tiene la responsabilidad de dar respuesta y solución a las diversas problemáticas con la comprensión de las regulaciones fiscales, las cuales no responden a los intereses de los distintos contribuyentes y muchas veces entran en contradicción con las políticas internas del país, los principios de la tributación y de los mismos asesores tributarios. Se concluye que existe la necesidad de integrar dentro de los planes de estudio de los programas de contaduría pública un curso de hermenéutica jurídica que contribuya a la comprensión de las normas sustanciales y procedimentales del sistema tributario.

Purpose Breast cancer (BC) is the most common malignancy among women and prognosis is strongly influenced by tumor subtype. Neoadjuvant chemotherapy (NAC) is the standard treatment for both locally advanced- and early-stage triple-negative and Her2-positive BC. Pathologic complete response (pCR) to NAC is an important predictor of patient outcomes. Neutrophil-to-lymphocyte-ratio (NLR) in peripheral blood is associated with prognosis in various malignancies. Here, we investigated the value of the pretreatment NLR as a response predictor in neoadjuvant-treated patients with BC. Methods A retrospective chart analysis of 862 patients with invasive BC treated with NAC at the Heidelberg University Hospital during 2003–2015 was conducted. NLR was calculated as the ratio of the absolute neutrophil and lymphocyte counts in peripheral blood, and pCR was defined as absence of invasive or in situ carcinoma in breast and axillary lymph nodes. Results A total of 151 patients with invasive BC who underwent NAC were included in this study. NLR tended to be higher in the pCR group than the non-pCR group (p p = 0.048) in patients with luminal B/Her2-negative tumors. Further, we found a significant difference in NLR according to remission status in postmenopausal patients (2.861 vs. 2.313, respectively; p = 0.043). Conclusion NLR was significantly higher only for patients achieving pCR in the Luminal B/Her2-negative and postmenopausal subgroups. Hence, NLR is a candidate additional predictive factor in patients with Luminal B/Her2-negative BC.

El desarrollo de esta parte de la investigación permite la identificación de los beneficios tributarios establecidos en el Código de Rentas del Municipio de Circasia, reglamentado a través de los Acuerdos 024 de 2014 y 001 de 2015, dentro de los cuales se destacan las exenciones, exclusiones, tasas y bases especiales en determinados tributos; la clasificación de las Pymes del Municipio de acuerdo con las actividades económicas y las normas que las regulan, tipificando el sector empresarial al que pertenecen, la personería jurídica mediante la cual se constituyeron y su posicionamiento con respecto a las demás medianas y pequeñas empresas coexistentes en la región; y por último, el análisis de la aplicabilidad de los beneficios tributarios por parte de las Pymes que están localizadas en el municipio de Circasia, Departamento del Quindío, entre los años gravables 2015 y 2020. La investigación se realiza bajo el método descriptivo utilizando un enfoque mixto, considerando una parte cualitativa dado que existe una referenciación conceptual, teórica y documental; y otra parte cuantitativa, por el uso de métodos estadísticos y tabulación de datos para la presentación de los resultados; además se utiliza como instrumento de recolección de la información una encuesta (32 preguntas) estructurada por secciones de acuerdo con el tipo de beneficio tributario, que le fue entregada a la población empresarial objetivo, permitiendo a través de su aplicación obtener datos relevantes, como la limitada acción de la administración en torno a difundir información en cuanto a los beneficios tributarios existentes en el Código de Rentas, el significativo aprovechamiento de parte de las entidades sobre los beneficios que incentivan el pronto pago de algunos impuestos, a la vez que se expusieron cuestiones como los beneficios no aprovechables, dado su restringido público objetivo, así como también la gran utilidad que presentan los beneficios como herramienta del Estado a la hora de incentivar el desarrollo económico, generar empleo, subsanar la carga impositiva y permitirle sobrellevar algunas de las diferentes problemáticas que tienen las empresas en el ejercicio de su actividad, siempre que los incentivos estén diseñados de manera que sean aprovechables y se dé la aplicación de los mismos por parte de las sociedades.

Purpose In the ACOSOG Z0011 trial, completing axillary lymph node dissection (cALND) did not benefit patients with T1–T2 cN0 early breast cancer and 1–2 positive sentinel lymph nodes (SLN) undergoing breast-conserving surgery (BCT). This paper reports cALND rates in the clinical routine for patients who had higher (T3–T4) tumor stages and/or underwent mastectomy but otherwise met the ACOSOG Z0011 eligibility criteria. Aim of this study is to determine cALND time trends and non-sentinel axillary metastases (NSAM) rates to estimate occult axillary tumor burden. Methods Data were included from patients treated in 179 German breast cancer centers between 2008 and 2015. Time-trend rates were analyzed for cALND of patients with T3–T4 tumors separated for BCT and mastectomy and regarding presence of axillary macrometastases or micrometastases. Results Data were available for 188,909 patients, of whom 19,009 were identified with 1–2 positive SLN. Those 19,009 patients were separated into 4 cohorts: (1) Patients with T1–T2 tumors receiving BCT (ACOSOG Z0011 eligible; n = 13,741), (2) T1–T2 with mastectomy (n = 4093), (3) T3–T4 with BCT (n = 269), (4) T3–T4 with mastectomy (n = 906). Among patients with T3–T4 tumors, cALND rates declined from 2008 to 2015: from 88.2 to 62.6% for patients receiving mastectomy and from 96.6 to 58.1% in patients receiving BCT. Overall rates for any NSAM after cALND for cohorts 1–4 were 33.4%, 42.3%, 46.9%, 58.8%, respectively. Conclusions The cALND rates have decreased substantially in routine care in patients with ‘extended’ ACOSOG Z0011 eligibility criteria. Axillary tumor burden is higher in these patients than in the ACOSOG Z0011 trial.

Purpose Circulating miRNAs can provide valid prognostic and predictive information for breast cancer diagnosis and subsequent management. They may comprise quintessential biomarkers that can be obtained minimally invasively from liquid biopsy in metastatic breast cancer patients. Therefore, they would be clinically crucial for monitoring therapy response, with the goal of detecting early relapse. This study investigated miRNA expression in patients with early and/or late relapse, and the predictive value for assessing overall (OS) and progression-free survival (PFS). Methods Forty-seven patients with metastatic breast cancer from the University Women’s Hospital Heidelberg were enrolled in this study. Expression of miR-200a, miR-200b, miR-200c, miR-141, and miR-429 was analyzed by RT-qPCR before a new line of systemic therapy and after the first cycle of a respective therapy. Tumor response was assessed every 3 months using the RECIST criteria. Statistical analysis focused on the relation of miR-200s expression and early vs. late cancer relapse in relation to systemic treatment. The association of miRNAs with PFS and OS was investigated. Results Before starting a new line of systemic therapy, miR-429 (p = 0.024) expression was significantly higher in patients with early relapse (PFS ≤ 4 months) than in patients with late relapse (PFS > 4 months). After one cycle of systemic therapy, miR-200a (p = 0.039), miR-200b (p = 0.003), miR-141 (p = 0.017), and miR-429 (p = 0.010) expression was higher in early than in late progressive cancer. In addition, 4 out of 5 miR-200 family members (miR-200a, miR-200b, miR-141, and miR-429) predicted PFS (p = 0.048, p = 0.008, p = 0.026, and p = 0.016, respectively). Patients with heightened miRNA levels showed a significant reduction in OS and PFS. Conclusion Circulating miR-200s were differentially expressed among patients with late and/or early relapse. 4 of 5 members of the miR-200 family predicted significantly early relapse after systemic treatment. Our results encourage the use of circulating miR-200s as valuable prognostic biomarkers during metastatic breast cancer therapy.

Background: Women with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NACT) or hormone-receptor (HR)-positive/HER2-negative breast cancer (BC) with a CPS (clinical and post treatment pathological stage) +EG (estrogen receptor status and grade) score ≥3 or score 2 and nodal involvement after NACT (ypN+) are at high risk of recurrence. SG is approved by the Food and Drug Administration for the treatment of patients with metastatic TNBC who received at least two prior therapies for metastatic disease and has shown activity in heavily pretreated patients with metastatic HR-positive/HER2-negative BC. SG may represent a new option against residual disease after NACT. Trial Design: SASCIA is a phase III, prospective, international, multicenter, randomized, open label, parallel group study (NCT04595565) of the GBG in collaboration with the AGO-B. Eligible patients must have received taxane-based NACT for 16 weeks, including 6 weeks of a taxane. Patients should have centrally confirmed HER2-negative BC (IHC score 0-1 or FISH negative) and either HR-negative ( ypT1mi or HR-positive (≥1%), with a CPS+EG score ≥3 or CPS+EG score 2 and ypN+ using local ER and grade assessed on core biopsies taken before NACT. Radiotherapy should be delivered before study treatment start. Patients are randomized 1:1 to receive either SG 10 mg/kg body weight (days 1, 8 q3w for eight cycles) or treatment of physician´s choice (capecitabine 2000 mg/m² day 1-14 q21 or platinum-based chemotherapy i.e. carboplatin AUC 5 q3w or AUC 1.5 weekly for eight 3 weekly cycles or observation). Randomization is stratified by HR status (positive, negative) and nodal involvement after NACT (ypN+, ypN0). Endocrine-based therapy will be administered according to local guidelines in patients with HR-positive BC. The primary endpoint is invasive disease-free survival (iDFS). Secondary endpoints include comparison of overall survival (OS, key secondary endpoint), distant disease-free survival, locoregional recurrences-free interval, safety, compliance, iDFS and OS according to stratified and - predefined subgroups, patient reported outcome, and quality of life between treatment arms. As of 21st June 2021, 57/1200 patients have been randomized in Germany. Citation Format: Frederik Marmé, Marcus Schmidt, Jenny Furlanetto, Carsten Denkert, Anthony Goncalves, Elmar Stickeler, Mattea Reinisch, Silvia Antolín, Toralf Reimer, Wolfgang Janni, Philippe Aftimos, Michael Untch, Laura Michel, Marija Balic, Bruno Sinn, Volker Möbus, Patrick Morris, Laura Schöllhorn, Sabine Schmatloch, Julia Rey, Sibylle Loibl. Phase III postneoadjuvant study evaluating sacituzumab govitecan (SG), an antibody drug conjugate in primary HER2-negative breast cancer patients with high relapse risk after standard neoadjuvant treatment - SASCIA [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-02-01.

International audience; As Jan-Lucas Schanze shows, probability-based surveys better reflect the share of people “85 years and over” in samples than quota surveys. But they still seem to be affected by the same selection/self-selection biases as quota surveys. In particular, they include an excessively high share of voters, even in segments with high abstentionism, such as the “85 years and over” group. They do not enable the detection of the beginning of the decline in participation from the age of 70, or the acceleration of the abstention trend from the age of 80, let alone the collapse of participation among those “85 years and over.” They are no more effective than quota surveys in identifying the evolution of participation with aging. This finding seems to confirm that the issue here is not so much sampling techniques as particularly powerful selection/self-selection biases in the oldest age-group: among those “85 years and over,” individuals who are healthier, cognitively higher functioning, and therefore most active socially and politically most readily agree to participate in surveys. As a result, subsamples of the elderly and very elderly are unrepresentative of the age-groups they are supposed to represent.; Comme le montre Jan-Lucas Schanze, les enquêtes fondées sur la probabilité reflètent mieux la proportion de personnes de « 85 ans et plus » dans les échantillons que les enquêtes sur les quotas. Mais elles semblent toujours être touchées par les mêmes biais de sélection et d'autosélection que les enquêtes sur les quotas. En particulier, elles comprennent une proportion excessivement élevée d'électeurs, même dans des segments où l'abstentionnisme est élevé, comme le groupe des « 85 ans et plus ». Elles ne permettent pas de détecter le début du déclin de la participation à partir de 70 ans, ni l'accélération de la tendance à l'abstention à partir de 80 ans, sans parler de l'effondrement de la participation parmi les « 85 ans et plus ». Elles ne sont pas plus efficaces que les enquêtes sur les quotas pour déterminer l'évolution de la participation au vieillissement. Cette constatation semble confirmer que le problème ici ne concerne pas tant les techniques d'échantillonnage que les biais de sélection et d'auto-sélection particulièrement puissants dans le groupe d'âge le plus âgé : parmi les personnes de « 85 ans et plus », les personnes qui sont en meilleure santé, qui ont un fonctionnement cognitif plus élevé et qui, par conséquent, sont les plus actives sur le plan social et politiquement sont plus à même d'accepter de participer à des enquêtes. Par conséquent, les sous-échantillons de personnes âgées et de personnes très âgées ne sont pas représentatifs des groupes d'âge qu'ils sont censés représenter.

El propósito del artículo es investigar el corpus literario sobre el papel de la Responsabilidad Social Pública (RSP) para contribuir desarrollo sostenible; discute la necesidad de la transformación a un enfoque unido de todos los niveles de la sociedad y sus organizaciones desde diferentes índoles para lograr desde una administración pública socialmente responsable la implementación de la Agenda 2030, en la acción de estrategias para que los Estados Miembros le apunten a aportar a la consolidación de los Objetivos del Desarrollo Sostenible (ODS). El diseño metodológico, se trabajó desde un enfoque cualitativo con un alcance hermenéutico-comprensivo, realizando un análisis observacional y retrospectivo sobre una base de datos que contiene 44 publicaciones en idioma inglés publicados entre 2001 y 2020 (febrero). Como hallazgos y resultados, el análisis bibliográfico identificó que la investigación sobre la RSP está vinculada al concepto de la sostenibilidad y centrada en la importancia de las acciones tangibles, por lo cual se logró establecer una relación desde los atributos primordiales que fomentan la gestión socialmente responsable de la administración pública de las entidades de los Estados Parte, hacia la contribución de los ODS de una manera inclusiva, sostenible y resiliente, lo cual constituye un compromiso universal. En síntesis, este documento contribuye a la literatura sobre RSP como un conductor para los ODS, proporcionando una revisión sistemática de la literatura sobre estos temas bajo la perspectiva de la gestión socialmente responsable para un desarrollo sostenible.

International audience

Specific biological properties of those circulating cancer cells that are the origin of brain metastases (BM) are not well understood. Here, single circulating breast cancer cells were fate-tracked during all steps of the brain metastatic cascade in mice after intracardial injection over weeks. A novel in vivo two-photon microscopy methodology was developed that allowed to determine the specific cellular and molecular features of breast cancer cells that homed in the brain, extravasated, and successfully established a brain macrometastasis. Those BM-initiating breast cancer cells (BMIC) were mainly originating from a slow-cycling subpopulation that included only 16% to 20% of all circulating cancer cells. BMICs showed enrichment of various markers of cellular stemness. As a proof of principle for the principal usefulness of this approach, expression profiling of BMICs versus non-BMICs was performed, which revealed upregulation of NDRG1 in the slow-cycling BMIC subpopulation in one BM model. Here, BM development was completely suppressed when NDRG1 expression was downregulated. In accordance, in primary human breast cancer, NDRG1 expression was heterogeneous, and high NDRG1 expression was associated with shorter metastasis-free survival. In conclusion, our data identify temporary slow-cycling breast cancer cells as the dominant source of brain and other metastases and demonstrates that this can lead to better understanding of BMIC-relevant pathways, including potential new approaches to prevent BM in patients. Implications: Cancer cells responsible for successful brain metastasis outgrowth are slow cycling and harbor stemness features. The molecular characteristics of these metastasis-initiating cells can be studied using intravital microscopy technology.

Due to its rarity, there are no randomized trials investigating the outcome of adjuvant radiotherapy in MBC. This study reports on patient and tumor characteristics of 41 consecutive MBC patients treated between 1990 and 2018 and on clinical outcomes after surgical resection of tumors and adjuvant radiotherapy of the chest wall or breast. Local control (LC), locoregional control (LRC), overall survival (OS), disease-free survival (DFS), and toxicity were evaluated. After a median follow-up of 80 months (95% CI: 14.6&ndash, 213.8 months) there was only one recurrence, in a patient&rsquo, s locoregional lymph nodes 17 months after start of radiotherapy, resulting in an LC rate of 100% at 5 years and a 5-year LRC rate of 97.4% (standard deviation (SD): 0.025). Five-year DFS and OS rates were 64.6% (SD: 0.085) and 57.2% (SD: 0.082), respectively. Adjuvant radiotherapy was tolerated well without high-grade (CTCAE grade &gt, II) adverse events. After tumor resection and adjuvant radiotherapy, LC and LRC rates in MBC patients are excellent and comparable to results found for female breast cancer (FBC) patients. However, as patients are often diagnosed with locally advanced, higher-risk tumors, distant recurrences remain the major failure pattern.

International audience; While the food supply question virtually disappeared from the agenda of the cities of the developed world after World War II, a growing number of cities in the developing and developed world alike are now giving it their attention (Chapter “ Cities’ Strategies for Sustainable Food and the Levers They Mobilize”). That renewed focus has been brought about by a food supply discourse that seeks to promote a sustainable urban policy (Pothukuchi and Kaufman 2000). In that context, food supply has come to be at the heart of a new category of public urban action—sustainable development—that has now been widely undertaken in local public action (Béal et al. 2011).

Background Salvage treatment for recurrent brain metastases (BM) of solid cancers is challenging due to the high symptomatic burden and the limited local treatment options. Methods Patients with recurrent BM with no option for further local therapies were retrospectively identified from BM databases. Bevacizumab-based treatment was initiated as a salvage treatment. Radiological imaging before and after bevacizumab-based treatment was reevaluated for treatment response using the Response Assessment in Neuro-Oncology (RANO) BM criteria. Results Twenty-two patients (36.4% male) with recurrent BM from breast cancer (40.9%), colorectal cancer (31.8%), or lung cancer (27.3%) were identified. Previous BM-directed therapies were radiosurgery in 16/22 (72.7%) patients, whole-brain radiotherapy in 8/22 (36.4%), and neurosurgical resection in 11/22 (50.0%). Time since BM diagnosis to initiation of bevacizumab treatment was 16.5 months. Of 22 patients 14 (63.6%) received concurrent systemic therapies. Neurological symptom improvement could be achieved in 14/22 (63.6%) and stabilization in 6/22 (27.3%) patients, resulting in a clinical benefit in 20/22 (90.9%) patients. Steroids could be reduced or stopped in 15/22 (68.2%) patients. Rate of improvement on T1-weighted imaging was 15/19 (78.9%; median reduction: −26.0% ± 32.9) and 19/20 (95%; median reduction: −36.2% ± 22.2) on T2-weighted FLAIR imaging. According to RANO-BM best response was partial response in 7/19 (36.8%), stable disease in 9/19 (47.3%), and progressive disease in 3/19 (15.7%) patients. Median CNS-specific progression-free survival was 8 months and median overall survival after initiation of bevacizumab treatment was 17 months. Conclusions Bevacizumab-based treatment had clinically relevant intracranial activity in the vast majority of patients suffering from recurrent, symptomatic BM. The data supports a prospective clinical trial of bevacizumab as a salvage treatment in BM.

The transmission of underwater sound and its interactions with the sediment layer of the ocean floor has impacts across many areas of naval warfare. There are numerous physical parameters influencing acoustics at the water-sediment interface. A numerical modeling approach, using the equation of motion from Biot’s theory of poroelasticity is useful in determining if variations in the physical parameters will have implications on acoustic reflections, transmissions, and bottom loss. These modeling efforts can inform decisions related to antisubmarine warfare, mine warfare, and hydrography as well as other areas of U.S. naval operations. This thesis examined variations in characteristic pore size, dynamic viscosity, permeability, and porosity and assessed the impacts of these variations on the acoustic reflection and transmission coefficients and bottom loss at the water-sediment interface. Our analyses determined that porosity and characteristic pore size, individually, had the largest impacts on the acoustical transmissions within the water-sediment interface for the parameters studied. Future research is suggested to study the interrelationships of these modeled physical parameters. http://archive.org/details/poroelasticprope1094564852 Lieutenant Commander, United States Navy Approved for public release; distribution is unlimited.

El presente articulo analiza las practicas y evidencias de rse en las grandes empresas familiares pertenecientes al sector secundario que desarrollan una actividad economica industrial en la ciudad de Manizales, ubicada en el departamento de Caldas, Colombia, las cuales realizan procesos de internacionalizacion por medio de su responsabilidad social, de esta manera se centra el interes en los casos empresariales Casa Luker —Sucesores de Jose Jesus Restrepo & Cia. S. A.— y Riduco S.A.

En el sistema tributario Colombiano, el Impuesto al Valor Agregado (IVA), es el impuesto indirecto que representa el rubro más significativo, después del impuesto directo a las rentas de losdiferentes contribuyentes de la Nación. No sólo es necesario el impuesto a las ventas para incrementar los recursos del Estado a nivel Nacional, sino que a través de la historia ha tomado importancia también en los recursos de los entes territoriales en el desarrollo de políticas económicas de capital, de inversión y desarrollo social., Primeria edición

CILAS pioneer in deformable mirrors proposes an overview of its technologies which are the monomorph and the piezo-stack mirrors. Recent performances of these mirrors are presented followed by the next evolutions that can be foreseen.