Multimodal augmented reality system for surgical microscopy

Image-guided, computer-assisted neurosurgery has emerged to improve localization and targeting, to provide a better anatomic definition of the surgical field, and to decrease invasiveness. Usually, in image-guided surgery, a computer displays the surgical field in a CT/MR environment, using axial, coronal or sagittal views, or even a 3D representation of the patient. Such a system forces the surgeon to look away from the surgical scene to the computer screen. Moreover, this kind of information, being pre-operative imaging, can not be modified during the operation, so it remains valid for guidance in the first stage of the surgical procedure, and mainly for rigid structures like bones. In order to solve the two constraints mentioned before, we are developing an ultrasoundguided surgical microscope. Such a system takes the advantage that surgical microscopy and ultrasound systems are already used in neurosurgery, so it does not add more complexity to the surgical procedure. We have integrated an optical tracking device in the microscope and an augmented reality overlay system with which we avoid the need to look away from the scene, providing correctly aligned surgical images with sub-millimeter accuracy. In addition to the standard CT and 3D views, we are able to track an ultrasound probe, and using a previous calibration and registration of the imaging, the image obtained is correctly projected to the overlay system, so the surgeon can always localize the target and verify the effects of the intervention. Several tests of the system have been already performed to evaluate the accuracy, and clinical experiments are currently in progress in order to validate the clinical usefulness of the system.

Semaphorins guide PerPlexeD endothelial cells

Abrogation of the endothelial cell-specific semaphorin receptor PlexinD1 in zebrafish and mouse reveals semaphorin functions selectively affecting the cardiovascular system. Neuropilins team up with PlexinD1 to form a novel endothelial receptor complex for class 3 semaphorins.

Female patients with atherosclerotic lesions of the lower limbs. Not all are alike

BACKGROUND: Data on female patients with atherosclerotic peripheral arterial disease (PAD) are scarce, and limited primarily to the elderly population with multilevel disease. In this longitudinal observational study we compare female patients below 60 years of age with isolated lesions at the aortic bifurcation or focal superficial femoral artery disease. PATIENTS AND METHODS: Analysis is based on consecutive series of 43 female patients with PAD limited to the aortoiliac bifurcation (n = 28, group I) or an isolated femoral segment at the adductor channel (n = 15, group II) seen in a tertiary referral center between 1998 and 2000. The first assessment provided baseline data, with follow up data obtained at this study. Traditional risk factors, carotid artery disease and clinical outcome (mortality, cardiovascular events, vascular re-intervention rate, PAD progression) were evaluated over an interval of 5 (2 to 8) years. RESULTS: Female patients with aortic disease [group I] were younger (51.8 +/- 7.7 vs. 56.7 +/- 7.6 years in group II; p = 0.048), presented a more masculine phenotype, and smoked significantly more often (82% vs. 40%; p = 0.007). Arterial hypertension and diabetes mellitus were more common in group II, though it missed statistical significance (p = 0.068 and p = 0.085). Cardiovascular and limb outcome were comparable in both groups of female patients, while carotid artery disease was more severe in group I (i.e., carotid plaques in 71 vs. 53%). CONCLUSION: Our data support previous findings that cigarette smoking is a stronger risk factor for aortic disease as compared to femoral disease in younger female patients, with the strongest effect of smoking on a localized region of the aortic bifurcation.

Theoretical considerations to the verification of dynamic multileaf collimated fields with a SLIC-type portal image detector

The verification possibilities of dynamically collimated treatment beams with a scanning liquid ionization chamber electronic portal image device (SLIC-EPID) are investigated. The ion concentration in the liquid of a SLIC-EPID and therefore the read-out signal is determined by two parameters of a differential equation describing the creation and recombination of the ions. Due to the form of this equation, the portal image detector describes a nonlinear dynamic system with memory. In this work, the parameters of the differential equation were experimentally determined for the particular chamber in use and for an incident open 6 MV photon beam. The mathematical description of the ion concentration was then used to predict portal images of intensity-modulated photon beams produced by a dynamic delivery technique, the sliding window approach. Due to the nature of the differential equation, a mathematical condition for 'reliable leaf motion verification' in the sliding window technique can be formulated. It is shown that the time constants for both formation and decay of the equilibrium concentration in the chamber is in the order of seconds. In order to guarantee reliable leaf motion verification, these time constants impose a constraint on the rapidity of the image-read out for a given maximum leaf speed. For a leaf speed of 2 cm s(-1), a minimum image acquisition frequency of about 2 Hz is required. Current SLIC-EPID systems are usually too slow since they need about a second to acquire a portal image. However, if the condition is fulfilled, the memory property of the system can be used to reconstruct the leaf motion. It is shown that a simple edge detecting algorithm can be employed to determine the leaf positions. The method is also very robust against image noise.

Evaluation of 41calcium as a new approach to assess changes in bone metabolism: effect of a bisphosphonate intervention in postmenopausal women with low bone mass

A new technique was evaluated to identify changes in bone metabolism directly at high sensitivity through isotopic labeling of bone Ca. Six women with low BMD were labeled with 41Ca up to 700 days and treated for 6 mo with risedronate. Effect of treatment on bone could be identified using 41Ca after 4-8 wk in each individual. INTRODUCTION: Isotopic labeling of bone using 41Ca, a long-living radiotracer, has been proposed as an alternative approach for measuring changes in bone metabolism to overcome current limitations of available techniques. After isotopic labeling of bone, changes in urinary 41Ca excretion reflect changes in bone Ca balance. The aim of this study was to validate this new technique against established measures. Changes in bone Ca balance were induced by giving a bisphosphonate. MATERIALS AND METHODS: Six postmenopausal women with diagnosed osteopenia/osteoporosis received a single oral dose of 100 nCi 41Ca for skeleton labeling. Urinary 41Ca/40Ca isotope ratios were monitored by accelerator mass spectrometry up to 700 days after the labeling process. Subjects received 35 mg risedronate per week for 6 mo. Effect of treatment was monitored using the 41Ca signal in urine and parallel measurements of BMD by DXA and biochemical markers of bone metabolism in urine and blood. RESULTS: Positive response to treatment was confirmed by BMD measurements, which increased for spine by +3.0% (p = 0.01) but not for hip. Bone formation markers decreased by -36% for bone alkaline phosphatase (BALP; p = 0.002) and -59% for procollagen type I propeptides (PINP; p = 0.001). Urinary deoxypyridinoline (DPD) and pyridinoline (PYD) were reduced by -21% (p = 0.019) and -23% (p = 0.009), respectively, whereas serum and urinary carboxy-terminal teleopeptides (CTXs) were reduced by -60% (p = 0.001) and -57.0% (p = 0.001), respectively. Changes in urinary 41Ca excretion paralleled findings for conventional techniques. The urinary 41Ca/40Ca isotope ratio was shifted by -47 +/- 10% by the intervention. Population pharmacokinetic analysis (NONMEM) of the 41Ca data using a linear three-compartment model showed that bisphosphonate treatment reduced Ca transfer rates between the slowly exchanging compartment (bone) and the intermediate fast exchanging compartment by 56% (95% CI: 45-58%). CONCLUSIONS: Isotopic labeling of bone using 41Ca can facilitate human trials in bone research by shortening of intervention periods, lowering subject numbers, and having easier conduct of cross-over studies compared with conventional techniques.

Expression and hypoxic regulation of the endothelin system in endocrine cells of human and rat pancreatic islets

CONTEXT: The success of pancreatic islet transplantation depends largely on the capacity of the islet graft to survive the initial phase immediately after transplantation until revascularization is completed. Endothelin-1 (ET-1) is a strong vasoconstrictor which has been involved in solid organ graft failure but is also known to be a potent mitogenic/anti-apoptotic factor which could also potentially enhance the survival of the transplanted islets. OBJECTIVE: Characterization of the endothelin system with regard to a potential endothelin agonist/antagonist treatment. DESIGN: Regulated expression of the endothelin system in human and rat pancreatic islets and beta-cell lines was assessed by means of immunohistochemistry, competition binding studies, western blot, RT-PCR, real-time PCR and transplant studies. RESULTS: ET-1, ETA- and ETB-receptor immunoreactivity was identified in the endocrine cells of human and rat pancreatic islets. The corresponding mRNA was detectable in rat beta-cell lines and isolated rat and human pancreatic islets. Competition binding studies on rat islets revealed binding sites for both receptor types. ET-1 stimulated the phosphorylation of mitogen-activated protein kinase, which was prevented by ETA- and ETB-receptor antagonists. After exposure to hypoxia equal to post-transplant environment oxygen tension, mRNA levels of ET-1 and ETB-receptor of human islets were robustly induced whereas ETA-receptor mRNA did not show significant changes. Immunostaining signals for ET-1 and ETA-receptor of transplanted rat islets were markedly decreased when compared to native pancreatic sections. CONCLUSIONS: In pancreatic islets, ET-1 and its receptors are differentially expressed by hypoxia and after transplantation. Our results provide the biological basis for the study of the potential use of endothelin agonists/antagonists to improve islet transplantation outcome.

A system for 3-D reconstruction of a patient-specific surface model from calibrated X-ray images

This paper presents a system for 3-D reconstruction of a patient-specific surface model from calibrated X-ray images. Our system requires two X-ray images of a patient with one acquired from the anterior-posterior direction and the other from the axial direction. A custom-designed cage is utilized in our system to calibrate both images. Starting from bone contours that are interactively identified from the X-ray images, our system constructs a patient-specific surface model of the proximal femur based on a statistical model based 2D/3D reconstruction algorithm. In this paper, we present the design and validation of the system with 25 bones. An average reconstruction error of 0.95 mm was observed.

Life and death partners: apoptosis, autophagy and the cross-talk between them

It is not surprising that the demise of a cell is a complex well-controlled process. Apoptosis, the first genetically programmed death process identified, has been extensively studied and its contribution to the pathogenesis of disease well documented. Yet, apoptosis does not function alone to determine a cell's fate. More recently, autophagy, a process in which de novo-formed membrane-enclosed vesicles engulf and consume cellular components, has been shown to engage in a complex interplay with apoptosis. In some cellular settings, it can serve as a cell survival pathway, suppressing apoptosis, and in others, it can lead to death itself, either in collaboration with apoptosis or as a back-up mechanism when the former is defective. The molecular regulators of both pathways are inter-connected; numerous death stimuli are capable of activating either pathway, and both pathways share several genes that are critical for their respective execution. The cross-talk between apoptosis and autophagy is therefore quite complex, and sometimes contradictory, but surely critical to the overall fate of the cell. Furthermore, the cross-talk is a key factor in the outcome of death-related pathologies such as cancer, its development and treatment.

Marginal fit of cemented and screw-retained crowns incorporated on the Straumann (ITI) Dental Implant System: an in vitro study

AIM: The aim of this study was to assess the marginal fit of crowns on the Straumann (ITI) Dental Implant System with special consideration of different casting dental materials. MATERIAL AND METHODS: Sixty porcelain-fused-to-metal crowns were fabricated: 18 crowns on standard cone abutments with an impression cylinder, partially prefabricated analogs, no coping and screw-retained (A); 18 crowns on solid abutments without an impression device, no analogs, no coping and cemented (B); and 18 crowns on solid abutments using an impression transfer cap, an analog with a shoulder, no coping and cemented (C). In each group, six crowns were made on epoxy mastercasts (Bluestar), six on synthetic plaster (Moldasynt) and six on super hard stone (Fujirock). Six additional crowns were fabricated with the transversal screw retention system onto the Octa system with impression transfer caps, metal analogs, gold copings and screw-retained (D). Impregum was used as impression material. Crowns of B and C were cemented with KetacCem. Crowns of A and D were fixed with an occlusal screw torqued at 15 N cm. Crowns were embedded, cut and polished. Under a light microscope using a magnification of x 100, the distance between the crown margin (CM) and the shoulder (marginal gap, MG) and the distance between the CM and the end of the shoulder (crown length, CL) was measured. RESULTS: MGs were 15.4+/-13.2 microm (A), 21.2+/-23.1 microm (B), 11+/-12.1 microm (C) and 10.4+/-9.3 microm (D). No statistically significantly differences using either of the casting materials were observed. CLs were -21.3+/-24.8 microm (A), 3+/-28.9 microm (B), 0.5+/-22 microm (C) and 0.1+/-15.8 microm (D). Crowns were shorter on synthetic casting materials compared with stone casts (P<0.005). CONCLUSIONS: CMs fit precisely with both cemented and screw-retained versions as well as when using no, partial or full analogs.

A systematic review of the clinical performance of CAD/CAM single-tooth restorations

PURPOSE: This systematic review sought to determine the long-term clinical survival rates of single-tooth restorations fabricated with computer-aided design/computer-assisted manufacture (CAD/CAM) technology, as well as the frequency of failures depending on the CAD/CAM system, the type of restoration, the selected material, and the luting agent. MATERIALS AND METHODS: An electronic search from 1985 to 2007 was performed using two databases: Medline/PubMed and Embase. Selected keywords and well-defined inclusion and exclusion criteria guided the search. All articles were first reviewed by title, then by abstract, and subsequently by a full text reading. Data were assessed and extracted by two independent examiners. The pooled results were statistically analyzed and the overall failure rate was calculated by assuming a Poisson-distributed number of events. In addition, reported failures were analyzed by CAD/CAM system, type of restoration, restorative material, and luting agent. RESULTS: From a total of 1,957 single-tooth restorations with a mean exposure time of 7.9 years and 170 failures, the failure rate was 1.75% per year, estimated per 100 restoration years (95% CI: 1.22% to 2.52%). The estimated total survival rate after 5 years of 91.6% (95% CI: 88.2% to 94.1%) was based on random-effects Poisson regression analysis. CONCLUSIONS: Long-term survival rates for CAD/CAM single-tooth Cerec 1, Cerec 2, and Celay restorations appear to be similar to conventional ones. No clinical studies or randomized clinical trials reporting on other CAD/CAM systems currently used in clinical practice and with follow-up reports of 3 or more years were found at the time of the search.

Supporting Task-oriented Navigation in IDEs with Configurable HeatMaps

Mainstream IDEs generally rely on the static structure of a software project to support browsing and navigation. We propose HeatMaps, a simple but highly configurable technique to enrich the way an IDE displays the static structure of a software system with additional kinds of information. A heatmap highlights software artifacts according to various metric values, such as bright red or pale blue, to indicate their potential degree of interest. We present a prototype system that implements heatmaps, and we describe an initial study that assesses the degree to which different heatmaps effectively guide developers in navigating software.

A simple asthma prediction tool for preschool children with wheeze or cough

BACKGROUND Many preschool children have wheeze or cough, but only some have asthma later. Existing prediction tools are difficult to apply in clinical practice or exhibit methodological weaknesses. OBJECTIVE We sought to develop a simple and robust tool for predicting asthma at school age in preschool children with wheeze or cough. METHODS From a population-based cohort in Leicestershire, United Kingdom, we included 1- to 3-year-old subjects seeing a doctor for wheeze or cough and assessed the prevalence of asthma 5 years later. We considered only noninvasive predictors that are easy to assess in primary care: demographic and perinatal data, eczema, upper and lower respiratory tract symptoms, and family history of atopy. We developed a model using logistic regression, avoided overfitting with the least absolute shrinkage and selection operator penalty, and then simplified it to a practical tool. We performed internal validation and assessed its predictive performance using the scaled Brier score and the area under the receiver operating characteristic curve. RESULTS Of 1226 symptomatic children with follow-up information, 345 (28%) had asthma 5 years later. The tool consists of 10 predictors yielding a total score between 0 and 15: sex, age, wheeze without colds, wheeze frequency, activity disturbance, shortness of breath, exercise-related and aeroallergen-related wheeze/cough, eczema, and parental history of asthma/bronchitis. The scaled Brier scores for the internally validated model and tool were 0.20 and 0.16, and the areas under the receiver operating characteristic curves were 0.76 and 0.74, respectively. CONCLUSION This tool represents a simple, low-cost, and noninvasive method to predict the risk of later asthma in symptomatic preschool children, which is ready to be tested in other populations.

Successful Careers in Football – Findings of a Person-Oriented Study

A successful career in football is the result of the appropriate interaction between different aspects of an individual’s life, since the various areas and phases of one’s life depend on each other. An endogenous causal relationship exists throughout a person’s entire history (Mayer, 1990). In particular, their family, work and sports career must be tuned to each other. The transition from the initial stages of education (compulsory schooling) to vocational training, which coincides with the beginning of the selection for the national youth teams, is a particularly critical phase (Wylleman, Theeboom, & Lavallee, 2004). In order to do justice to the overall life situation of a young sports talent during this transition phase, we have adopted a holistic perspective and follow Bergman, Magnusson and El-Khouri (2003) in using a person-oriented and systemic approach. In doing so, our main focus lies on the person-environment system. This overall system is made up of various subsystems, consisting of several operating factors which interact with one another. The different levels to which these operating factors are expressed lead to observable patterns, which can be summarised in the form of types. Particularly promising types can therefore be identified and the developmental process can be described. Former players on the Swiss U16 to U21 national football teams, born between 1981 and 1987 (n=159), were interviewed concerning their careers, and the operating factors school/vocational training, family support and sports environment were examined. With the help of the LICUR method (Linking of Clusters after removal of Residue) (Bergman et al., 2003), developmental types were identified which were promising in terms of achieving top performance in adulthood. A range of developmental types and anti-types emerge for the transition from the under-15 phase to the over-16 phase. One particularly promising type is observed in the over-16 phase, for which the operating factors education, family support and participation in national U16 to U18 teams have slightly above-average scores, with scores that are well above average in the sports environment.

Effects of Gender on the Incidence of Cardiac Tamponade Following Catheter Ablation of Atrial Fibrillation: Results from a Worldwide Survey in 34,943 AF Ablation Procedures.

BACKGROUND -Cardiac tamponade is the most dramatic complication observed during atrial fibrillation (AF) ablation and the leading cause of procedure-related mortality. Female gender is a known risk factor for complications during AF ablation; however, it is unknown whether women have a higher risk of tamponade. METHODS AND RESULTS -A systematic Medline search was used to locate academic electrophysiologic (EP) centers that reported cases of tamponade occurring during AF ablation. Centers were asked to provide information on cases of acute tamponade according to gender and their mode of management including any case of related mortality. Nineteen EP centers provided information on 34,943 ablation procedures involving 25,261 (72%) males. Overall 289 (0.9%) cases of tamponade were reported: 120 (1.24%) in females and 169 (0.67%) in males (odds ratio 1.83, P<0.001). There was a reciprocal association between center volume and the occurrence of tamponade with substantial lower risk in high volume centers. Most cases of tamponade occurred during catheter manipulation or ablation; females tended to develop more tamponades during transseptal catheterization. No gender difference in the mode of management was observed. However, 16% cases of tamponade required surgery with lower rates in high volume centers. Three cases of tamponade (1%) culminated in death. CONCLUSIONS -Tamponade during AF ablation procedures is relatively rare. Women have an almost twofold higher risk for developing this complication. The risk of tamponade among women decreases substantially in high volume centers. Surgical back-up and acute management skills for treating tamponade are important in centers performing AF ablation.

Cost-effectiveness of ticagrelor and generic clopidogrel in patients with acute coronary syndrome in Switzerland

QUESTION UNDER STUDY The aim of this study was to evaluate the cost-effectiveness of ticagrelor and generic clopidogrel as add-on therapy to acetylsalicylic acid (ASA) in patients with acute coronary syndrome (ACS), from a Swiss perspective. METHODS Based on the PLATelet inhibition and patient Outcomes (PLATO) trial, one-year mean healthcare costs per patient treated with ticagrelor or generic clopidogrel were analysed from a payer perspective in 2011. A two-part decision-analytic model estimated treatment costs, quality-adjusted life years (QALYs), life years and the cost-effectiveness of ticagrelor and generic clopidogrel in patients with ACS up to a lifetime at a discount of 2.5% per annum. Sensitivity analyses were performed. RESULTS Over a patient's lifetime, treatment with ticagrelor generates an additional 0.1694 QALYs and 0.1999 life years at a cost of CHF 260 compared with generic clopidogrel. This results in an Incremental Cost Effectiveness Ratio (ICER) of CHF 1,536 per QALY and CHF 1,301 per life year gained. Ticagrelor dominated generic clopidogrel over the five-year and one-year periods with treatment generating cost savings of CHF 224 and 372 while gaining 0.0461 and 0.0051 QALYs and moreover 0.0517 and 0.0062 life years, respectively. Univariate sensitivity analyses confirmed the dominant position of ticagrelor in the first five years and probabilistic sensitivity analyses showed a high probability of cost-effectiveness over a lifetime. CONCLUSION During the first five years after ACS, treatment with ticagrelor dominates generic clopidogrel in Switzerland. Over a patient's lifetime, ticagrelor is highly cost-effective compared with generic clopidogrel, proven by ICERs significantly below commonly accepted willingness-to-pay thresholds.