The new bern PET cyclotron, its research beam line, and the development of an innovative beam monitor detector

The new Bern cyclotron laboratory aims at industrial radioisotope production for PET diagnostics and multidisciplinary research by means of a specifically conceived beam transfer line, terminated in a separate bunker. In this framework, an innovative beam monitor detector based on doped silica and optical fibres has been designed, constructed, and tested. Scintillation light produced by Ce and Sb doped silica fibres moving across the beam is measured, giving information on beam position, shape, and intensity. The doped fibres are coupled to commercial optical fibres, allowing the read-out of the signal far away from the radiation source. This general-purpose device can be easily adapted for any accelerator used in medical applications and is suitable either for low currents used in hadrontherapy or for currents up to a few μA for radioisotope production, as well as for both pulsed and continuous beams.

Psychosocial aspects in cardiac rehabilitation: From theory to practice. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation of the European Society of Cardiology

A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health-related quality of life (HRQoL) and prognosis in patients with established CHD. PSRFs may also act as barriers to lifestyle changes and treatment adherence and may moderate the effects of cardiac rehabilitation (CR). Furthermore, there appears to be a bidirectional interaction between PSRFs and the cardiovascular system. Stress, anxiety and depression affect the cardiovascular system through immune, neuroendocrine and behavioural pathways. In turn, CHD and its associated treatments may lead to distress in patients, including anxiety and depression. In clinical practice, PSRFs can be assessed with single-item screening questions, standardised questionnaires, or structured clinical interviews. Psychotherapy and medication can be considered to alleviate any PSRF-related symptoms and to enhance HRQoL, but the evidence for a definite beneficial effect on cardiac endpoints is inconclusive. A multimodal behavioural intervention, integrating counselling for PSRFs and coping with illness should be included within comprehensive CR. Patients with clinically significant symptoms of distress should be referred for psychological counselling or psychologically focused interventions and/or psychopharmacological treatment. To conclude, the success of CR may critically depend on the interdependence of the body and mind and this interaction needs to be reflected through the assessment and management of PSRFs in line with robust scientific evidence, by trained staff, integrated within the core CR team.

A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome.

Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents.

Fast Prediction of Femoral Biomechanics Using Supervised Machine Learning and Statistical Shape Modeling

Finite element (FE) analysis is an important computational tool in biomechanics. However, its adoption into clinical practice has been hampered by its computational complexity and required high technical competences for clinicians. In this paper we propose a supervised learning approach to predict the outcome of the FE analysis. We demonstrate our approach on clinical CT and X-ray femur images for FE predictions ( FEP), with features extracted, respectively, from a statistical shape model and from 2D-based morphometric and density information. Using leave-one-out experiments and sensitivity analysis, comprising a database of 89 clinical cases, our method is capable of predicting the distribution of stress values for a walking loading condition with an average correlation coefficient of 0.984 and 0.976, for CT and X-ray images, respectively. These findings suggest that supervised learning approaches have the potential to leverage the clinical integration of mechanical simulations for the treatment of musculoskeletal conditions.

Multiple imputation for missing continuous and dichotomous data: The effects of patterns of missingness and variable correlations on type I error with small samples

The purpose of this study is to investigate the effects of predictor variable correlations and patterns of missingness with dichotomous and/or continuous data in small samples when missing data is multiply imputed. Missing data of predictor variables is multiply imputed under three different multivariate models: the multivariate normal model for continuous data, the multinomial model for dichotomous data and the general location model for mixed dichotomous and continuous data. Subsequent to the multiple imputation process, Type I error rates of the regression coefficients obtained with logistic regression analysis are estimated under various conditions of correlation structure, sample size, type of data and patterns of missing data. The distributional properties of average mean, variance and correlations among the predictor variables are assessed after the multiple imputation process. ^ For continuous predictor data under the multivariate normal model, Type I error rates are generally within the nominal values with samples of size n = 100. Smaller samples of size n = 50 resulted in more conservative estimates (i.e., lower than the nominal value). Correlation and variance estimates of the original data are retained after multiple imputation with less than 50% missing continuous predictor data. For dichotomous predictor data under the multinomial model, Type I error rates are generally conservative, which in part is due to the sparseness of the data. The correlation structure for the predictor variables is not well retained on multiply-imputed data from small samples with more than 50% missing data with this model. For mixed continuous and dichotomous predictor data, the results are similar to those found under the multivariate normal model for continuous data and under the multinomial model for dichotomous data. With all data types, a fully-observed variable included with variables subject to missingness in the multiple imputation process and subsequent statistical analysis provided liberal (larger than nominal values) Type I error rates under a specific pattern of missing data. It is suggested that future studies focus on the effects of multiple imputation in multivariate settings with more realistic data characteristics and a variety of multivariate analyses, assessing both Type I error and power. ^

Der Krieg in Südafrika : seine Ursache und Führung

Arthur Conan Doyle

(Table 1) Distribution of ichthyolith subtypes at DSDP Hole 62-464

At Site 464, a 308-meter-deep hole was drilled on the Hess Rise (39°51.64'N, 173°53.33'E; water depth 4637 m). The upper strata consist of siliceous clay and oozes of Pleistocene, Pliocene, and possibly latest Miocene ages (36 m) and the lower strata are Albian chert, chalk, and marlstone (219 m). The middle part of the stratigraphic section is pelagic brown clay (53 m) which is essentially barren of microfossils except for ichthyoliths. At the base of this middle unit in Core 10 is a recrystallized Cretaceous radiolarian assemblage and an impoverished late Miocene nannofossil assemblage. Fifteen samples from Cores 6 through 10 in the middle unit and three samples from the overlying siliceous clay were examined for ichthyoliths.

High-resolution ice thickness and bed topography of a land-terminating section of the Greenland Ice Sheet, with links to GeoTIFFs and text files

We present ice thickness and bed topography maps with a high spatial resolution (250-500 m) of a land-terminating section of the Greenland Ice Sheet derived from ground-based and airborne radar surveys. The data have a total area of ~12 000 km^2 and cover the whole ablation area of the outlet glaciers of Isunnguata Sermia, Russell, Leverett, Ørkendalen and Isorlersuup up to the long-term mass balance equilibrium line altitude at ~1600 m above sea level. The bed topography shows highly variable subglacial trough systems, and the trough of Isunnguata Sermia Glacier is overdeepened and reaches an elevation of ~500 m below sea level. The ice surface is smooth and only reflects the bedrock topography in a subtle way, resulting in a highly variable ice thickness. The southern part of our study area consists of higher bed elevations compared to the northern part. The compiled data sets of ground-based and airborne radar surveys cover one of the most studied regions of the Greenland Ice Sheet and can be valuable for detailed studies of ice sheet dynamics and hydrology.

Preliminary ichthyolith biostratigraphy and age profiles at DSDP Sites 91-595 and 91-596

Seventy meters of Cenozoic and Mesozoic pelagic clay cored at DSDP Sites 595 and 596 provide the basis for a preliminary analysis of ichthyolith biostratigraphy in the southwest Pacific. A most likely order of the more reliable ichthyolith events is compared with a synthesis of ichthyolith biostratigraphy in the North Pacific and with dated composite ranges. The resultant preliminary ichthyolith stratigraphy suggests that the Cenozoic is represented by the upper 20 m at Site 596 and 16 to 22 m at Site 595. Mixing of taxa precludes a clear recognition of the Cretaceous/Tertiary boundary at Site 595. The occurrence of 13 newly described subtypes is recorded in Mesozoic sediments at Sites 595 and 596. These new subtypes and previously described Mesozoic forms may be useful for recognizing Mesozoic subdivisions when their occurrences in sequences dated by other microfossils are investigated.

Inorganic geochemistry, epoch and water content in sediments at DSDP Hole 91-595A

This chapter summarizes the principal results of drilling at Deep Sea Drilling Project (DSDP) Site 595, where the Ngendei Seismic Experiment and the emplacement of DARPA's Marine Seismic System (MSS) were carried out. Background and objectives for this work are presented in the introductory chapter to this volume. Interpretation of the seismic experiment and drilling results are presented in subsequent parts of this volume. The chapter also provides a detailed operational summary of the successful deployment of the MSS during Leg 91.

Cretaceous-Tertiary ichthyoliths of brown clay intervals

The pattern of ichthyolith distribution established in sequences with stratigraphies based on calcareous or siliceous microfossils is used to provide age correlations for three deep-sea pelagic clay intervals that lack the better known microfossils. At Site 637, approximately 25 m of brown clay in Cores 103-637A-21R through 103-637A-23R underlies upper Miocene sediments and is of Paleocene to early Eocene age. At Site 639, 1.7 m of brown clay in Core 103-639C-2R is Eocene to Oligocene. At Site 640, 3.5 m of clay in Cores 103-640A-1R and 103-640A-2R contains a Cretaceous to Paleocene sequence, with the Cretaceous/Tertiary boundary between 84 and 103 cm in Section 103-640A-2R-1.

Ocean acidification impacts on sperm mitochondrial membrane potential bring sperm swimming behaviour near its tipping point

Broadcast spawning marine invertebrates are susceptible to environmental stressors such as climate change, as their reproduction depends on the successful meeting and fertilization of gametes in the water column. Under near-future scenarios of ocean acidification, the swimming behaviour of marine invertebrate sperm is altered. We tested whether this was due to changes in sperm mitochondrial activity by investigating the effects of ocean acidification on sperm metabolism and swimming behaviour in the sea urchin Centrostephanus rodgersii. We used a fluorescent molecular probe (JC-1) and flow cytometry to visualize mitochondrial activity (measured as change in mitochondrial membrane potential, MMP). Sperm MMP was significantly reduced in delta pH -0.3 (35% reduction) and delta pH -0.5 (48% reduction) treatments, whereas sperm swimming behaviour was less sensitive with only slight changes (up to 11% decrease) observed overall. There was significant inter-individual variability in responses of sperm swimming behaviour and MMP to acidified seawater. We suggest it is likely that sperm exposed to these changes in pH are close to their tipping point in terms of physiological tolerance to acidity. Importantly, substantial inter-individual variation in responses of sperm swimming to ocean acidification may increase the scope for selection of resilient phenotypes, which, if heritable, could provide a basis for adaptation to future ocean acidification.