Design-based stereology: Planning, volumetry and sampling are crucial steps for a successful study

Quantitative data obtained by means of design-based stereology can add valuable information to studies performed on a diversity of organs, in particular when correlated to functional/physiological and biochemical data. Design-based stereology is based on a sound statistical background and can be used to generate accurate data which are in line with principles of good laboratory practice. In addition, by adjusting the study design an appropriate precision can be achieved to find relevant differences between groups. For the success of the stereological assessment detailed planning is necessary. In this review we focus on common pitfalls encountered during stereological assessment. An exemplary workflow is included, and based on authentic examples, we illustrate a number of sampling principles which can be implemented to obtain properly sampled tissue blocks for various purposes.

Computer-aided operation planning and 3-dimensional osteotomy guidance for alveolar distraction

Objectives: In alveolar distraction, in cases of severe atrophy in particular, it is often difficult to perform osteotomies in order to make a transport segment in optimal size and shape. Moreover care must be taken, not to damage the closely locating anato- mical structures such as the maxillary sinus, the inferior alveolar nerve, and the roots of the neighboring teeth. For setting ideal osteotomy lines exactly, we have developed a CT-based preoperative planning tool. Methods: 3-dimensional visual reconstruction of the jaw is created from the preoperative CT scans (1.0-mm slice thick- ness). Using the image-processing software Mimics (Materialise, Yokohama, Japan), various procedures of virtual cutting are simulated first to determine optimal osteotomy lines and to design an ideal transport segment. After the computer planning, data from the virtual solid model are transferred to a rapid prototype model, and a guiding splint is made to transfer the planned surgical simulation to the actual surgery. Results: The method was used in a case of severe atrophy of the anterior maxilla. The patient had a large maxillary sinus requir- ing a precise osteotomy in this critical area. Using the splint allowing a 3-dimensional guidance, alveolar osteotomies were easily done to achieve a transport segment in sufficient dimen- sion as planned, and any perforation of the maxillary sinus could be avoided. Finally the alveolar distraction of 10mm has suc- cessfully been performed. Conclusion: The preoperative planning method and the guiding splint described here are useful in problematic cases requiring an extremely precise osteotomy due to lack of bony space.

Improved VMAT planning for head and neck tumors with an advanced optimization algorithm

OBJECTIVE In this study, the "Progressive Resolution Optimizer PRO3" (Varian Medical Systems) is compared to the previous version "PRO2" with respect to its potential to improve dose sparing to the organs at risk (OAR) and dose coverage of the PTV for head and neck cancer patients. MATERIALS AND METHODS For eight head and neck cancer patients, volumetric modulated arc therapy (VMAT) treatment plans were generated in this study. All cases have 2-3 phases and the total prescribed dose (PD) was 60-72Gy in the PTV. The study is mainly focused on the phase 1 plans, which all have an identical PD of 54Gy, and complex PTV structures with an overlap to the parotids. Optimization was performed based on planning objectives for the PTV according to ICRU83, and with minimal dose to spinal cord, and parotids outside PTV. In order to assess the quality of the optimization algorithms, an identical set of constraints was used for both, PRO2 and PRO3. The resulting treatment plans were investigated with respect to dose distribution based on the analysis of the dose volume histograms. RESULTS For the phase 1 plans (PD=54Gy) the near maximum dose D2% of the spinal cord, could be minimized to 22±5 Gy with PRO3, as compared to 32±12Gy with PRO2, averaged for all patients. The mean dose to the parotids was also lower in PRO3 plans compared to PRO2, but the differences were less pronounced. A PTV coverage of V95%=97±1% could be reached with PRO3, as compared to 86±5% with PRO2. In clinical routine, these PRO2 plans would require modifications to obtain better PTV coverage at the cost of higher OAR doses. CONCLUSION A comparison between PRO3 and PRO2 optimization algorithms was performed for eight head and neck cancer patients. In general, the quality of VMAT plans for head and neck patients are improved with PRO3 as compared to PRO2. The dose to OARs can be reduced significantly, especially for the spinal cord. These reductions are achieved with better PTV coverage as compared to PRO2. The improved spinal cord sparing offers new opportunities for all types of paraspinal tumors and for re-irradiation of recurrent tumors or second malignancies.

Huntington's like conditions in China, A review of published Chinese cases

Background: Knowledge about HD in China is lacking in the international literature. We have therefore analyzed the Chinese literature to thoroughly explore the clinical characteristics of Huntington disease in China. Methods: A computer-based online search of China National Knowledge Infrastructure was performed to review case reports concerning HD published between January 1980 and April of 2011, and the clinical characteristics were extracted. Results: A total of 92 studies involving 279 patients (157 males and 122 females) were collected, 82.0% of which were from provinces of North China. Most of the cases (97.8%) had a family history of HD, and paternal inheritance (65.5%) was higher than maternal inheritance (34.5%). Onset age was 35.8 (± 11.8) years, death occurred with 45.6 (± 13.5) years after a course of 11.6 (± 5.6) years. Involuntary movements were the most frequent reported presentation (found in 52.3%, including 64.4% in the entire body, 19.8% in the upper limbs, and 13.7% in the head and face). Psychiatric symptoms at onset were reported in 16.1%, and cognitive impairment in 1.8%. With disease progression, 99.6% of patients had abnormal movements, 67.9% cognitive impairment, and 35.0% suffered psychiatric symptoms. Of the reported patients, only 22 underwent IT15 gene testing with positive results. Conclusion: HD is a well-reported entity in Chinese medical literature, however, only a small number of instances have been proven by molecular diagnosis. Most of the features resemble what is known in other countries. The highly predominant motor presentation, and the higher male prevalence as well as the apparent concentration in Northern China may be due to observational bias. There is therefore a need to prospectively examine cohorts of patients with appropriate comprehensive assessment tools including genetic testing.

New technology enables high precision multislit collimators for microbeam radiation therapy

During the past decade microbeam radiation therapy has evolved from preclinical studies to a stage in which clinical trials can be planned, using spatially fractionated, highly collimated and high intensity beams like those generated at the x-ray ID17 beamline of the European Synchrotron Radiation Facility. The production of such microbeams typically between 25 and 100 microm full width at half maximum (FWHM) values and 100-400 microm center-to-center (c-t-c) spacings requires a multislit collimator either with fixed or adjustable microbeam width. The mechanical regularity of such devices is the most important property required to produce an array of identical microbeams. That ensures treatment reproducibility and reliable use of Monte Carlo-based treatment planning systems. New high precision wire cutting techniques allow the fabrication of these collimators made of tungsten carbide. We present a variable slit width collimator as well as a single slit device with a fixed setting of 50 microm FWHM and 400 microm c-t-c, both able to cover irradiation fields of 50 mm width, deemed to meet clinical requirements. Important improvements have reduced the standard deviation of 5.5 microm to less than 1 microm for a nominal FWHM value of 25 microm. The specifications of both devices, the methods used to measure these characteristics, and the results are presented.

Fast parallel kriging-based stepwise uncertainty reduction with application to the identification of an excursion set

Stepwise uncertainty reduction (SUR) strategies aim at constructing a sequence of points for evaluating a function  f in such a way that the residual uncertainty about a quantity of interest progressively decreases to zero. Using such strategies in the framework of Gaussian process modeling has been shown to be efficient for estimating the volume of excursion of f above a fixed threshold. However, SUR strategies remain cumbersome to use in practice because of their high computational complexity, and the fact that they deliver a single point at each iteration. In this article we introduce several multipoint sampling criteria, allowing the selection of batches of points at which f can be evaluated in parallel. Such criteria are of particular interest when f is costly to evaluate and several CPUs are simultaneously available. We also manage to drastically reduce the computational cost of these strategies through the use of closed form formulas. We illustrate their performances in various numerical experiments, including a nuclear safety test case. Basic notions about kriging, auxiliary problems, complexity calculations, R code, and data are available online as supplementary materials.

Online health information seeking in the context of the medical consultation in Switzerland

A growing number of patients search for medical information on the Internet. Understanding how they use the Internet is important, as this might impact their health, patient-practitioner roles, and general health care provision. In this article, we illustrate the motives of online health information seeking in the context of the doctor-patient relationship in Switzerland. We conducted semistructured interviews with patients who searched for health information online before or after a medical consultation. Findings suggest that patients searched for health information online to achieve the goals of preparing for the consultation, complementing it, validating it, and/or challenging its outcome. The initial motivations for online health information seeking are identified in the needs for acknowledgment, reduction of uncertainty, and perspective. Searching health information online was also encouraged by personal and contextual factors, that is, a person's sense of self-responsibility and the opportunity to use the Internet. Based on these results, we argue that online health information seeking is less concerned with what happens during the consultation than with what happens before or after it, in the sociocultural context.

Geographic information system-based decision support for soil conservation planning in Tajikistan

Soil erosion on sloping agricultural land poses a serious problem for the environment, as well as for production. In areas with highly erodible soils, such as those in loess zones, application of soil and water conservation measures is crucial to sustain agricultural yields and to prevent or reduce land degradation. The present study, carried out in Faizabad, Tajikistan, was designed to evaluate the potential of local conservation measures on cropland using a spatial modelling approach to provide decision-making support for the planning of spatially explicit sustainable land use. A sampling design to support comparative analysis between well-conserved units and other field units was established in order to estimate factors that determine water erosion, according to the Revised Universal Soil Loss Equation (RUSLE). Such factor-based approaches allow ready application using a geographic information system (GIS) and facilitate straightforward scenario modelling in areas with limited data resources. The study showed first that assessment of erosion and conservation in an area with inhomogeneous vegetation cover requires the integration of plot-based cover. Plot-based vegetation cover can be effectively derived from high-resolution satellite imagery, providing a useful basis for plot-wise conservation planning. Furthermore, thorough field assessments showed that 25.7% of current total cropland is covered by conservation measures (terracing, agroforestry and perennial herbaceous fodder). Assessment of the effectiveness of these local measures, combined with the RUSLE calculations, revealed that current average soil loss could be reduced through low-cost measures such as contouring (by 11%), fodder plants (by 16%), and drainage ditches (by 53%). More expensive measures such as terracing and agroforestry can reduce erosion by as much as 63% (for agroforestry) and 93% (for agroforestry combined with terracing). Indeed, scenario runs for different levels of tolerable erosion rates showed that more cost-intensive and technologically advanced measures would lead to greater reduction of soil loss. However, given economic conditions in Tajikistan, it seems advisable to support the spread of low-cost and labourextensive measures.

Surgical planning tool for robotically assisted hearing aid implantation

PURPOSE : For the facilitation of minimally invasive robotically performed direct cochlea access (DCA) procedure, a surgical planning tool which enables the surgeon to define landmarks for patient-to-image registration, identify the necessary anatomical structures and define a safe DCA trajectory using patient image data (typically computed tomography (CT) or cone beam CT) is required. To this end, a dedicated end-to-end software planning system for the planning of DCA procedures that addresses current deficiencies has been developed. METHODS :    Efficient and robust anatomical segmentation is achieved through the implementation of semiautomatic algorithms; high-accuracy patient-to-image registration is achieved via an automated model-based fiducial detection algorithm and functionality for the interactive definition of a safe drilling trajectory based on case-specific drill positioning uncertainty calculations was developed. RESULTS :    The accuracy and safety of the presented software tool were validated during the conduction of eight DCA procedures performed on cadaver heads. The plan for each ear was completed in less than 20 min, and no damage to vital structures occurred during the procedures. The integrated fiducial detection functionality enabled final positioning accuracies of [Formula: see text] mm. CONCLUSIONS :    Results of this study demonstrated that the proposed software system could aid in the safe planning of a DCA tunnel within an acceptable time.

The EVIDENT-trial: protocol and rationale of a multicenter randomized controlled trial testing the effectiveness of an online-based psychological intervention

BACKGROUND: Depressive disorders are among the leading causes of worldwide disability with mild to moderate forms of depression being particularly common. Low-intensity treatments such as online psychological treatments may be an effective way to treat mild to moderate depressive symptoms and prevent the emergence or relapse of major depression. METHODS/DESIGN: This study is a currently recruiting multicentre parallel-groups pragmatic randomized-controlled single-blind trial. A total of 1000 participants with mild to moderate symptoms of depression from various settings including in- and outpatient services will be randomized to an online psychological treatment or care as usual (CAU). We hypothesize that the intervention will be superior to CAU in reducing depressive symptoms assessed with the Personal Health Questionnaire (PHQ-9, primary outcome measure) following the intervention (12 wks) and at follow-up (24 and 48 wks). Further outcome parameters include quality of life, use of health care resources and attitude towards online psychological treatments. DISCUSSION: The study will yield meaningful answers to the question of whether online psychological treatment can contribute to the effective and efficient prevention and treatment of mild to moderate depression on a population level with a low barrier to entry. TRIAL REGISTRATION: Trial Registration Number: NCT01636752.

FORA - A Fuzzy Set Based Framework for Online Reputation Management

The Social Web offers increasingly simple ways to publish and disseminate personal or opinionated information, which can rapidly exhibit a disastrous influence on the online reputation of organizations. Based on social Web data, this study describes the building of an ontology based on fuzzy sets. At the end of a recurring harvesting of folksonomies by Web agents, the aggregated tags are purified, linked, and transformed to a so-called fuzzy grassroots ontology by means of a fuzzy clustering algorithm. This self-updating ontology is used for online reputation analysis, a crucial task of reputation management, with the goal to follow the online conversation going on around an organization to discover and monitor its reputation. In addition, an application of the Fuzzy Online Reputation Analysis (FORA) framework, lesson learned, and potential extensions are discussed in this article.