Response to neoadjuvant treatment of invasive ductal breast carcinomas including outcome evaluation: MRI analysis by an automatic CAD system in comparison to visual evaluation

BACKGROUND The aim of this study was to evaluate imaging-based response to standardized neoadjuvant chemotherapy (NACT) regimen by dynamic contrast-enhanced magnetic resonance mammography (DCE-MRM), whereas MR images were analyzed by an automatic computer-assisted diagnosis (CAD) system in comparison to visual evaluation. MRI findings were correlated with histopathologic response to NACT and also with the occurrence of metastases in a follow-up analysis. PATIENTS AND METHODS Fifty-four patients with invasive ductal breast carcinomas received two identical MRI examinations (before and after NACT; 1.5T, contrast medium gadoteric acid). Pre-therapeutic images were compared with post-therapeutic examinations by CAD and two blinded human observers, considering morphologic and dynamic MRI parameters as well as tumor size measurements. Imaging-assessed response to NACT was compared with histopathologically verified response. All clinical, histopathologic, and DCE-MRM parameters were correlated with the occurrence of distant metastases. RESULTS Initial and post-initial dynamic parameters significantly changed between pre- and post-therapeutic DCE-MRM. Visually evaluated DCE-MRM revealed sensitivity of 85.7%, specificity of 91.7%, and diagnostic accuracy of 87.0% in evaluating the response to NACT compared to histopathology. CAD analysis led to more false-negative findings (37.0%) compared to visual evaluation (11.1%), resulting in sensitivity of 52.4%, specificity of 100.0%, and diagnostic accuracy of 63.0%. The following dynamic MRI parameters showed significant associations to occurring metastases: Post-initial curve type before NACT (entire lesions, calculated by CAD) and post-initial curve type of the most enhancing tumor parts after NACT (calculated by CAD and manually). CONCLUSIONS In the accurate evaluation of response to neoadjuvant treatment, CAD systems can provide useful additional information due to the high specificity; however, they cannot replace visual imaging evaluation. Besides traditional prognostic factors, contrast medium-induced dynamic MRI parameters reveal significant associations to patient outcome, i.e. occurrence of distant metastases.

Die Inschriften des alten Friedhofs der israelitischen Gemeinde zu Frankfurt a. M.

mit einer Einl. von M. Horovitz

Randomized Trial to Evaluate Tandosporine in Geographic Atrophy Secondary to Age-Related Macular Degeneration: the GATE Study.

PURPOSE To determine the safety and efficacy of AL-8309B (tandospirone) in the management of patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and obtain standardized data on GA lesion growth progression. DESIGN Prospective, controlled, double-masked, randomized, multicenter phase 3 clinical trial. METHODS Setting: 48 clinical sites. PATIENTS Patients with GA associated with AMD were enrolled. All patients were followed for a minimum of 30 months, and up to 36 months. Intervention Procedures: Patients were randomized (1:1:1) to receive AL-8309B ophthalmic solution 1.0%, 1.75%, or vehicle, administered as a twice-daily topical ocular drop. MAIN OUTCOME MEASURES The primary efficacy endpoint was mean annualized lesion enlargement from baseline as assessed with fundus autofluorescence (FAF) imaging. RESULTS A total of 768 eyes of 768 patients were enrolled and treated with AL-8309B 1.0% (N=250), AL-8309B 1.75% (N=258), or vehicle (N= 260). An increase in mean lesion size was observed in both the AL-8309B and vehicle treatment groups, and growth rates were similar in all treatment groups. Annualized lesion growth rates were 1.73, 1.76 and 1.71 mm(2) for AL-8309B 1.0%, AL-8309B 1.75%, and vehicle, respectively. CONCLUSIONS AL-8309B 1.0% and 1.75% did not affect lesion growth in eyes with GA secondary to AMD. There were no clinically relevant safety issues identified for AL-8309B. The large natural history dataset from this study is a valuable repository for future comparisons.

Validation of the Valve Academic Research Consortium Bleeding Definition in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND The Valve Academic Research Consortium (VARC) has proposed a standardized definition of bleeding in patients undergoing transcatheter aortic valve interventions (TAVI). The VARC bleeding definition has not been validated or compared to other established bleeding definitions so far. Thus, we aimed to investigate the impact of bleeding and compare the predictivity of VARC bleeding events with established bleeding definitions. METHODS AND RESULTS Between August 2007 and April 2012, 489 consecutive patients with severe aortic stenosis were included into the Bern-TAVI-Registry. Every bleeding complication was adjudicated according to the definitions of VARC, BARC, TIMI, and GUSTO. Periprocedural blood loss was added to the definition of VARC, providing a modified VARC definition. A total of 152 bleeding events were observed during the index hospitalization. Bleeding severity according to VARC was associated with a gradual increase in mortality, which was comparable to the BARC, TIMI, GUSTO, and the modified VARC classifications. The predictive precision of a multivariable model for mortality at 30 days was significantly improved by adding the most serious bleeding of VARC (area under the curve [AUC], 0.773; 95% confidence interval [CI], 0.706 to 0.839), BARC (AUC, 0.776; 95% CI, 0.694 to 0.857), TIMI (AUC, 0.768; 95% CI, 0.692 to 0.844), and GUSTO (AUC, 0.791; 95% CI, 0.714 to 0.869), with the modified VARC definition resulting in the best predictivity (AUC, 0.814; 95% CI, 0.759 to 0.870). CONCLUSIONS The VARC bleeding definition offers a severity stratification that is associated with a gradual increase in mortality and prognostic information comparable to established bleeding definitions. Adding the information of periprocedural blood loss to VARC may increase the sensitivity and the predictive power of this classification.

A novel approach for assessing shifting cultivation dynamics in a regional conservation hotspot - insights from nort-eastern Madagascar

The north-eastern escarpment of Madagascar has been deemed a global hotspot of biodiversity due to its high levels of endemic speciesbeing heavily threatened by accelerated deforestation rates and landscape changes. The main concern for conservation of the remaining humid primary forests is the shifting cultivation practices of local smallholder farmers for rice production. According to the mainstream narrative, human population growth leads to a shortening of crop-fallow cycles and thus to the accelerated conversion of forests to agricultural land. However, little is currently known about the dynamic changes between forest and shifting cultivation systems at the regional level. Existing land cover change analyses in this area have so far only focused on binary forest to non-forest changes and have therefore failed to account for the dynamic nature of the change processes between forest and different agriculture land use systems. This can be partly explained by the significant challenge to delineate shifting cultivation systems on land cover maps using traditional remote sensing classification approaches. To address this gap we therefore applied a novel GIS approach, that was originally developed for the assessment of shifting cultivation dynamics in Laos and has so far never been applied elsewhere, to map shifting cultivation of different crop-fallow lengths as well as permanent agriculture land use at the regional level. Change analyses of land use maps between 1995 and 2011 allowed us to comprehend the general trends of land use trajectories and their spatial variation. This more detailed understanding of land use change dynamics is key to plan for successful interventions to slow forest loss while at the same time improving local livelihoods. We further believe that this approach holds great potential for conservation monitoring in this resource-rich but povertyprone conservation hotspot.

Retention in care during the first 3 years of antiretroviral therapy for women in Malawi's option B+ programme: an observational cohort study

Background Studies of Malawi's option B+ programme for HIV-positive pregnant and breastfeeding women have reported high loss to follow-up during pregnancy and at the start of antiretroviral therapy (ART), but few data exist about retention during breastfeeding and after weaning. We examined loss to follow-up and retention in care in patients in the option B+ programme during their first 3 years on ART. Methods We analysed two data sources: aggregated facility-level data about patients in option B+ who started ART between Oct 1, 2011, and June 30, 2012, at 546 health facilities; and patient-level data from 20 large facilities with electronic medical record system for HIV-positive women who started ART between Sept 1, 2011, and Dec 31, 2013, under option B+ or because they had WHO clinical stages 3 or 4 disease or had CD4 counts of less than 350 cells per μL. We used facility-level data to calculate representative estimates of retention and loss to follow-up. We used patient-level data to study temporal trends in retention, timing of loss to follow-up, and predictors of no follow-up and loss to follow-up. We defined patients who were more than 60 days late for their first follow-up visit as having no follow-up and patients who were more than 60 days late for a subsequent visit as being lost to follow-up. We calculated proportions and cumulative probabilities of patients who had died, stopped ART, had no follow-up, were lost to follow-up, or were retained alive on ART for 36 months. We calculated odds ratios and hazard ratios to examine predictors of no follow-up and loss to follow-up. Findings Analysis of facility-level data about patients in option B+ who had not transferred to a different facility showed retention in care to be 76·8% (20 475 of 26 658 patients) after 12 months, 70·8% (18 306 of 25 849 patients) after 24 months, and 69·7% (17 787 of 25 535 patients) after 36 months. Patient-level data included 29 145 patients. 14 630 (50·2%) began treatment under option B+. Patients in option B+ had a higher risk of having no follow-up and, for the first 2 years of ART, higher risk of loss to follow-up than did patients who started ART because they had CD4 counts less than 350 cells per μL or WHO clinical stage 3 or 4 disease. Risk of loss to follow-up during the third year was low and similar for patients retained for 2 years. Retention rates did not change as the option B+ programme matured. Interpretation Our data suggest that pregnant and breastfeeding women who start ART immediately after they are diagnosed with HIV can be retained on ART through the option B+ programme, even after many have stopped breastfeeding. Interventions might be needed to improve retention in the first year on ART in option B+. Funding Bill & Melinda Gates Foundation, Partnerships for Enhanced Engagement in Research Health, and National Institute of Allergy and Infectious Diseases.

Using the results of routine laboratory workplace surveillance activities to assess compliance with recommended biosafety guidelines

The biological safety profession has historically functioned within an environment based on recommended practices rather than regulations, so summary data on compliance or noncompliance with recommended practices is largely absent from the professional literature. The absence of safety performance outcome data is unfortunate since the concept of biosafety containment is based on a combination of facility based controls and workplace practices, and persistent failures in either type of controls could ultimately result in injury or death. In addition, the number of laboratories requiring biosafety containment is likely to grow significantly in the coming years in the wake of the terrorist events of 2001. In this study, the outcomes of 768 biosafety level 2 (BSL-2) safety surveys were analyzed for commonalities and trends. Items of non-compliance noted were classified as facility related or practice related. The most frequent item of noncompliance encountered was the failure to re-certify biosafety cabinetry. Not surprisingly, the preponderance of the other frequent items of non-compliance encountered were practice related, such as general housekeeping orderly, changes in compliance levels, as well as establish trends in the elements of items of non-compliance during the sequential survey period. The findings described in this study are significant because, for the first time, the outcomes of compliance with recommended biosafety practices can be characterized and thus used as the basis for focused interventions. Since biosafety is heavily reliant on adherence to specific safety practices, the ability to focus interventions on objectively identified practice-related items of non-compliance can assist in the reduction of worker risk in this area experiencing tremendous growth. The information described is also of heighten importance given the number of workplaces expected to involve potentially infectious agents in the coming years. ^

Solar radiation over and under sea ice and photographic quantification of Ice algal aggregates during the POLARSTERN cruise ARK-XXVII/3 (IceArc) in summer 2012

The ice cover of the Arctic Ocean has been changing dramatically in the last decades and the consequences for the sea-ice associated ecosystem remain difficult to assess. Algal aggregates underneath sea ice have been described sporadically but the frequency and distribution of their occurrence is not well quantified. We used upward looking images obtained by a remotely operated vehicle (ROV) to derive estimates of ice algal aggregate biomass and to investigate their spatial distribution. During the IceArc expedition (ARK-XXVII/3) of RV Polarstern in late summer 2012, different types of algal aggregates were observed floating underneath various ice types in the Central Arctic basins. Our results show that the floe scale distribution of algal aggregates in late summer is very patchy and determined by the topography of the ice underside, with aggregates collecting in dome shaped structures and at the edges of pressure ridges. The buoyancy of the aggregates was also evident from analysis of the aggregate size distribution. Different approaches used to estimate aggregate biomass yield a wide range of results. This highlights that special care must be taken when upscaling observations and comparing results from surveys conducted using different methods or on different spatial scales.

Solar irradiance over and under seasonal land-fast sea ice off Barrow, Alaska, in 2010

The amount of solar radiation transmitted through Arctic sea ice is determined by the thickness and physical properties of snow and sea ice. Light transmittance is highly variable in space and time since thickness and physical properties of snow and sea ice are highly heterogeneous on variable time and length scales. We present field measurements of under-ice irradiance along transects under undeformed land-fast sea ice at Barrow, Alaska (March, May, and June 2010). The measurements were performed with a spectral radiometer mounted on a floating under-ice sled. The objective was to quantify the spatial variability of light transmittance through snow and sea ice, and to compare this variability along its seasonal evolution. Along with optical measurements, snow depth, sea ice thickness, and freeboard were recorded, and ice cores were analyzed for chlorophyll a and particulate matter. Our results show that snow cover variability prior to onset of snow melt causes as much relative spatial variability of light transmittance as the contrast of ponded and white ice during summer. Both before and after melt onset, measured transmittances fell in a range from one third to three times the mean value. In addition, we found a twentyfold increase of light transmittance as a result of partial snowmelt, showing the seasonal evolution of transmittance through sea ice far exceeds the spatial variability. However, prior melt onset, light transmittance was time invariant and differences in under-ice irradiance were directly related to the spatial variability of the snow cover.