A next-generation tissue microarray (ngTMA) protocol for biomarker studies

Biomarker research relies on tissue microarrays (TMA). TMAs are produced by repeated transfer of small tissue cores from a 'donor' block into a 'recipient' block and then used for a variety of biomarker applications. The construction of conventional TMAs is labor intensive, imprecise, and time-consuming. Here, a protocol using next-generation Tissue Microarrays (ngTMA) is outlined. ngTMA is based on TMA planning and design, digital pathology, and automated tissue microarraying. The protocol is illustrated using an example of 134 metastatic colorectal cancer patients. Histological, statistical and logistical aspects are considered, such as the tissue type, specific histological regions, and cell types for inclusion in the TMA, the number of tissue spots, sample size, statistical analysis, and number of TMA copies. Histological slides for each patient are scanned and uploaded onto a web-based digital platform. There, they are viewed and annotated (marked) using a 0.6-2.0 mm diameter tool, multiple times using various colors to distinguish tissue areas. Donor blocks and 12 'recipient' blocks are loaded into the instrument. Digital slides are retrieved and matched to donor block images. Repeated arraying of annotated regions is automatically performed resulting in an ngTMA. In this example, six ngTMAs are planned containing six different tissue types/histological zones. Two copies of the ngTMAs are desired. Three to four slides for each patient are scanned; 3 scan runs are necessary and performed overnight. All slides are annotated; different colors are used to represent the different tissues/zones, namely tumor center, invasion front, tumor/stroma, lymph node metastases, liver metastases, and normal tissue. 17 annotations/case are made; time for annotation is 2-3 min/case. 12 ngTMAs are produced containing 4,556 spots. Arraying time is 15-20 hr. Due to its precision, flexibility and speed, ngTMA is a powerful tool to further improve the quality of TMAs used in clinical and translational research.

Computer Aided Surgery for Percutaneous Nephrolithotomy: Clinical Requirement Analysis and System Design

Percutaneous nephrolithotomy (PCNL) for the treatment of renal stones and other related renal diseases has proved its efficacy and has stood the test of time compared with open surgical methods and extracorporal shock wave lithotripsy. However, access to the collecting system of the kidney is not easy because the available intra-operative image modalities only provide a two dimensional view of the surgical scenario. With this lack of visual information, several punctures are often necessary which, increases the risk of renal bleeding, splanchnic, vascular or pulmonary injury, or damage to the collecting system which sometimes makes the continuation of the procedure impossible. In order to address this problem, this paper proposes a workflow for introduction of a stereotactic needle guidance system for PCNL procedures. An analysis of the imposed clinical requirements, and a instrument guidance approach to provide the physician with a more intuitive planning and visual guidance to access the collecting system of the kidney are presented.

Carbon pools and poverty peaks in Lao PDR

Reducing Emissions from Deforestation and forest Degradation and enhancing forest carbon stocks in developing countries (REDD+) is heavily promoted in Laos. REDD+ is often perceived as an opportunity to jointly address climate change and poverty and, therefore, could come timely for Laos to combine its prominent national target of poverty eradication with global climate mitigation efforts. Countrywide planning of the right approaches to REDD+ combined with poverty alleviation requires knowledge of the spatial combination of poverty and carbon stocks at the national level. This study combined spatial information on carbon stored in vegetation and on poverty and created carbon-poverty typologies for the whole country at the village level. We found that 11% of the villages of Laos have high to very high average village-level carbon stock densities and a predominantly poor population. These villages cover 20% of the territory and are characterized by low population density. Shifting cultivation areas in the northwestern parts of the country have a higher carbon mitigation potential than areas in the central and eastern highlands due to a more favorable climate. Finally, we found that in Laos the majority (58%) of poor people live in areas with low carbon stock densities without major potential to store carbon. Accordingly, REDD+ cannot be considered a core instrument for poverty alleviation. The carbon-poverty typologies presented here provide answers to basic questions related to planning and managing of REDD+. They could serve as a starting point for the design of systems to monitor both socioeconomic and environmental development at the national level.

Clinical evaluation of 3 overdenture concepts with tooth roots and implants: 2-year results

PURPOSE: In the present cohort study, overdentures with a combined root and implant support were evaluated and compared with either exclusively root- or implant-supported overdentures. Results of a 2-year follow-up period are reported, namely survival of implants, root copings, and prostheses, plus prosthetic complications, maintenance service, and patient satisfaction. MATERIALS AND METHODS: Fourteen patients were selected for the combined overdenture therapy and were compared with 2 patient groups in which either roots or implants provided overdenture support. Altogether, 14, 17, and 15 patients (in groups 1, 2, and 3, respectively) were matched with regard to age, sex, treatment time, and observation period. The mean age was around 67 years. Periodontal parameters were recorded, radiographs were taken, and all complications and failures were registered during the entire observation time. The patients answered a 9-item questionnaire by means of a visual analogue scale (VAS). RESULTS: One implant failed and 1 tooth root was removed following longitudinal root fracture. Periodontal/peri-implant parameters gave evidence of good oral hygiene for roots and implants, and slight crestal bone resorption was measured for both. Technical complications and service performed were significantly higher in the first year (P < .04) in all 3 groups and significantly higher in the tooth root group (P < .03). The results of the VAS indicated significantly lower scores for satisfaction, speaking ability, wearing comfort, and denture stability with combined or exclusive root support (P < .05 and .02, respectively). Initial costs of overdentures with combined or root support were 10% lower than for implant overdentures. CONCLUSION: The concept of combined root and implant support can be integrated into treatment planning and overdenture design for patients with a highly reduced dentition.