Generalized fuzzy clustering for segmentation of multi-spectral magnetic resonance images.

An integrated approach for multi-spectral segmentation of MR images is presented. This method is based on the fuzzy c-means (FCM) and includes bias field correction and contextual constraints over spatial intensity distribution and accounts for the non-spherical cluster's shape in the feature space. The bias field is modeled as a linear combination of smooth polynomial basis functions for fast computation in the clustering iterations. Regularization terms for the neighborhood continuity of intensity are added into the FCM cost functions. To reduce the computational complexity, the contextual regularizations are separated from the clustering iterations. Since the feature space is not isotropic, distance measure adopted in Gustafson-Kessel (G-K) algorithm is used instead of the Euclidean distance, to account for the non-spherical shape of the clusters in the feature space. These algorithms are quantitatively evaluated on MR brain images using the similarity measures.

Volume and shape in feature space on adaptive FCM in MRI segmentation.

Intensity non-uniformity (bias field) correction, contextual constraints over spatial intensity distribution and non-spherical cluster's shape in the feature space are incorporated into the fuzzy c-means (FCM) for segmentation of three-dimensional multi-spectral MR images. The bias field is modeled by a linear combination of smooth polynomial basis functions for fast computation in the clustering iterations. Regularization terms for the neighborhood continuity of either intensity or membership are added into the FCM cost functions. Since the feature space is not isotropic, distance measures, other than the Euclidean distance, are used to account for the shape and volumetric effects of clusters in the feature space. The performance of segmentation is improved by combining the adaptive FCM scheme with the criteria used in Gustafson-Kessel (G-K) and Gath-Geva (G-G) algorithms through the inclusion of the cluster scatter measure. The performance of this integrated approach is quantitatively evaluated on normal MR brain images using the similarity measures. The improvement in the quality of segmentation obtained with our method is also demonstrated by comparing our results with those produced by FSL (FMRIB Software Library), a software package that is commonly used for tissue classification.

Multi-Decadal Record of Ice Dynamics on Daugaard Jensen Gletscher, East Greenland, from Satellite Imagery and Terrestrial Measurements

The history of ice velocity and calving front position of Daugaard Jensen Gletscher, a large outlet glacier in East Greenland, is reconstructed from field measurements, aerial photography and satellite imagery for the period 1950-2001. The calving terminus of the glacier has remained in approximately the same position over the past similar to 50 years. There is no evidence of a change in ice motion between 1968 and 2001, based on a comparison of velocities derived from terrestrial surveying and feature tracking using sequential satellite images. Estimates of flux near the entrance to the fjord vs snow accumulation in the interior catchment show that Daugaard Jensen Gletscher has a small negative mass balance. This result is consistent with other mass-balance estimates for the inland region of the glacier.

Simulating Cortical Development as a Self Constructing Process: A Novel Multi-Scale Approach Combining Molecular and Physical Aspects

Current models of embryological development focus on intracellular processes such as gene expression and protein networks, rather than on the complex relationship between subcellular processes and the collective cellular organization these processes support. We have explored this collective behavior in the context of neocortical development, by modeling the expansion of a small number of progenitor cells into a laminated cortex with layer and cell type specific projections. The developmental process is steered by a formal language analogous to genomic instructions, and takes place in a physically realistic three-dimensional environment. A common genome inserted into individual cells control their individual behaviors, and thereby gives rise to collective developmental sequences in a biologically plausible manner. The simulation begins with a single progenitor cell containing the artificial genome. This progenitor then gives rise through a lineage of offspring to distinct populations of neuronal precursors that migrate to form the cortical laminae. The precursors differentiate by extending dendrites and axons, which reproduce the experimentally determined branching patterns of a number of different neuronal cell types observed in the cat visual cortex. This result is the first comprehensive demonstration of the principles of self-construction whereby the cortical architecture develops. In addition, our model makes several testable predictions concerning cell migration and branching mechanisms.

Contested Control: Irregular Transit Migrants in Europe

This presentation is about young migrants’ journeys with low chances of receiving asylum or any other type of residence in Europe. These migrants exhibit a highly complex migration pattern. First, these migrants are frequently in durable “transit” across Europe, moving back and forth between different states. Second, transit migrants must exhibit a high degree of flexibility, as they have to respond to suddenly changing conditions, such as work opportunities, rejection of asylum claims, detention or deportation. Third, transit migrants often switch between different legal statuses, such as asylum seeker, rejected asylum seeker, illegal worker or detainee. This throws them into a general state of uncertainty and psychological distress. The experience of these young adults shows a deep ambivalence between a sense of autonomy, on the one hand, and of profound hope- and powerlessness, on the other. This presentation explores the “fragmented journeys” of these migrants, by way of a multi-sited ethnographic approach and biographical interviews. It focuses on the lived experiences and the strategies of irregular migrants to find a way to reside in Europe in the context of an increasingly restrictive migration management.

A multi-model comparison of Atlantic multidecadal variability

A multi-model analysis of Atlantic multidecadal variability is performed with the following aims: to investigate the similarities to observations; to assess the strength and relative importance of the different elements of the mechanism proposed by Delworth et al. (J Clim 6:1993–2011, 1993) (hereafter D93) among coupled general circulation models (CGCMs); and to relate model differences to mean systematic error. The analysis is performed with long control simulations from ten CGCMs, with lengths ranging between 500 and 3600 years. In most models the variations of sea surface temperature (SST) averaged over North Atlantic show considerable power on multidecadal time scales, but with different periodicity. The SST variations are largest in the mid-latitude region, consistent with the short instrumental record. Despite large differences in model configurations, we find quite some consistency among the models in terms of processes. In eight of the ten models the mid-latitude SST variations are significantly correlated with fluctuations in the Atlantic meridional overturning circulation (AMOC), suggesting a link to northward heat transport changes. Consistent with this link, the three models with the weakest AMOC have the largest cold SST bias in the North Atlantic. There is no linear relationship on decadal timescales between AMOC and North Atlantic Oscillation in the models. Analysis of the key elements of the D93 mechanisms revealed the following: Most models present strong evidence that high-latitude winter mixing precede AMOC changes. However, the regions of wintertime convection differ among models. In most models salinity-induced density anomalies in the convective region tend to lead AMOC, while temperature-induced density anomalies lead AMOC only in one model. However, analysis shows that salinity may play an overly important role in most models, because of cold temperature biases in their relevant convective regions. In most models subpolar gyre variations tend to lead AMOC changes, and this relation is strong in more than half of the models.

Alpine lacustrine varved record reveals summer temperature as main control of glacier fluctuations over the past 2250 years

Glacier fluctuations are a key indicator of changing climate. Their reconstruction beyond historical times unravels glacier variability and its forcing factors on long time scales, which can considerably improve our understanding of the climate–glacier relationship. Here, we present a 2250-year-long reconstruction of particle-mass accumulation rates recorded in the lacustrine sediments of Lake Trüebsee (Central Swiss Alps) that are directly related to glacier extent, thus reflecting a continuous record of fluctuations of the upstream-located Titlis Glacier. Mass accumulation rate values show strong centennial to multi-centennial fluctuations and reveal 12 well-pronounced periods of enhanced values corresponding to times of maximum extent of the neighboring Lower Grindelwald Glacier. This result supports previous studies of proglacial lake sediments that documented high mass accumulation rate values during glacier advances. The strong variability in the Lake Trüebsee mass accumulation rate record thus represents a highly sensitive paleoclimatic archive, which mirrors rapid and pronounced feedbacks of Titlis Glacier to climatic changes over the past 2250years. The comparison of our data with independent paleo-temperature reconstructions from tree rings suggests that variations in mean summer temperature were the primary driving factor of fluctuations of Titlis Glacier. Also, advances of Titlis Glacier occurred during the grand solar minima (Dalton, Maunder, Spörer, Wolf) of the last millennium. This relation of glacier extent with summer temperature reveals strong evidence that the mass balance of this Alpine glacier is primarily controlled by the intensity of glacier melting during summer.

Survival with Newly Diagnosed Metastatic Prostate Cancer in the "Docetaxel Era": Data from 917 Patients in the Control Arm of the STAMPEDE Trial (MRC PR08, CRUK/06/019)

BACKGROUND Prostate cancer (PCa) is the second most common disease among men worldwide. It is important to know survival outcomes and prognostic factors for this disease. Recruitment for the largest therapeutic randomised controlled trial in PCa-the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial (STAMPEDE)-includes men with newly diagnosed metastatic PCa who are commencing long-term androgen deprivation therapy (ADT); the control arm provides valuable data for a prospective cohort. OBJECTIVE Describe survival outcomes, along with current treatment standards and factors associated with prognosis, to inform future trial design in this patient group. DESIGN, SETTING, AND PARTICIPANTS STAMPEDE trial control arm comprising men newly diagnosed with M1 disease who were recruited between October 2005 and January 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Overall survival (OS) and failure-free survival (FFS) were reported by primary disease characteristics using Kaplan-Meier methods. Hazard ratios and 95% confidence intervals (CIs) were derived from multivariate Cox models. RESULTS AND LIMITATIONS A cohort of 917 men with newly diagnosed M1 disease was recruited to the control arm in the specified interval. Median follow-up was 20 mo. Median age at randomisation was 66 yr (interquartile range [IQR]: 61-71), and median prostate-specific antigen level was 112 ng/ml (IQR: 34-373). Most men (n=574; 62%) had bone-only metastases, whereas 237 (26%) had both bone and soft tissue metastases; soft tissue metastasis was found mainly in distant lymph nodes. There were 238 deaths, 202 (85%) from PCa. Median FFS was 11 mo; 2-yr FFS was 29% (95% CI, 25-33). Median OS was 42 mo; 2-yr OS was 72% (95% CI, 68-76). Survival time was influenced by performance status, age, Gleason score, and metastases distribution. Median survival after FFS event was 22 mo. Trial eligibility criteria meant men were younger and fitter than general PCa population. CONCLUSIONS Survival remains disappointing in men presenting with M1 disease who are started on only long-term ADT, despite active treatments being available at first failure of ADT. Importantly, men with M1 disease now spend the majority of their remaining life in a state of castration-resistant relapse. PATIENT SUMMARY Results from this control arm cohort found survival is relatively short and highly influenced by patient age, fitness, and where prostate cancer has spread in the body.

Novel emboli protection system during cardiac surgery: a multi-center, randomized, clinical trial.

BACKGROUND Stroke is a major cause of morbidity and mortality during open-heart surgery. Up to 60% of intraoperative cerebral events are emboli induced. This randomized, controlled, multicenter trial is the first human study evaluating the safety and efficacy of a novel aortic cannula producing simultaneous forward flow and backward suction for extracting solid and gaseous emboli from the ascending aorta and aortic arch upon their intraoperative release. METHODS Sixty-six patients (25 females; 68±10 years) undergoing elective aortic valve replacement surgery, with or without coronary artery bypass graft surgery, were randomized to the use of the CardioGard (CardioGard Medical, Or-Yehuda, Israel) Emboli Protection cannula ("treatment") or a standard ("control") aortic cannula. The primary endpoint was the volume of new brain lesions measured by diffusion-weighted magnetic resonance imaging (DW-MRI), performed preoperatively and postoperatively. Device safety was investigated by comparisons of complications rate, namely neurologic events, stroke, renal insufficiency and death. RESULTS Of 66 patients (34 in the treatment group), 51 completed the presurgery and postsurgery MRI (27 in the treatment group). The volume of new brain lesion for the treatment group was (mean±standard error of the mean) 44.00±64.00 versus 126.56±28.74 mm3 in the control group (p=0.004). Of the treatment group, 41% demonstrated new postoperative lesions versus 66% in the control group (p=0.03). The complication rate was comparable in both groups. CONCLUSIONS The CardioGard cannula is safe and efficient in use during open-heart surgery. Efficacy was demonstrated by the removal of a substantial amount of emboli, a significant reduction in the volume of new brain lesions, and the percentage of patients experiencing new brain lesions.

Quality control for retinal OCT in multiple sclerosis: validation of the OSCAR-IB criteria.

BACKGROUND Retinal optical coherence tomography (OCT) permits quantification of retinal layer atrophy relevant to assessment of neurodegeneration in multiple sclerosis (MS). Measurement artefacts may limit the use of OCT to MS research. OBJECTIVE An expert task force convened with the aim to provide guidance on the use of validated quality control (QC) criteria for the use of OCT in MS research and clinical trials. METHODS A prospective multi-centre (n = 13) study. Peripapillary ring scan QC rating of an OCT training set (n = 50) was followed by a test set (n = 50). Inter-rater agreement was calculated using kappa statistics. Results were discussed at a round table after the assessment had taken place. RESULTS The inter-rater QC agreement was substantial (kappa = 0.7). Disagreement was found highest for judging signal strength (kappa = 0.40). Future steps to resolve these issues were discussed. CONCLUSION Substantial agreement for QC assessment was achieved with aid of the OSCAR-IB criteria. The task force has developed a website for free online training and QC certification. The criteria may prove useful for future research and trials in MS using OCT as a secondary outcome measure in a multi-centre setting.

Response profiles of murine spiral ganglion neurons on multi-electrode arrays.

OBJECTIVE Cochlear implants (CIs) have become the gold standard treatment for deafness. These neuroprosthetic devices feature a linear electrode array, surgically inserted into the cochlea, and function by directly stimulating the auditory neurons located within the spiral ganglion, bypassing lost or not-functioning hair cells. Despite their success, some limitations still remain, including poor frequency resolution and high-energy consumption. In both cases, the anatomical gap between the electrode array and the spiral ganglion neurons (SGNs) is believed to be an important limiting factor. The final goal of the study is to characterize response profiles of SGNs growing in intimate contact with an electrode array, in view of designing novel CI devices and stimulation protocols, featuring a gapless interface with auditory neurons. APPROACH We have characterized SGN responses to extracellular stimulation using multi-electrode arrays (MEAs). This setup allows, in our view, to optimize in vitro many of the limiting interface aspects between CIs and SGNs. MAIN RESULTS Early postnatal mouse SGN explants were analyzed after 6-18 days in culture. Different stimulation protocols were compared with the aim to lower the stimulation threshold and the energy needed to elicit a response. In the best case, a four-fold reduction of the energy was obtained by lengthening the biphasic stimulus from 40 μs to 160 μs. Similarly, quasi monophasic pulses were more effective than biphasic pulses and the insertion of an interphase gap moderately improved efficiency. Finally, the stimulation with an external electrode mounted on a micromanipulator showed that the energy needed to elicit a response could be reduced by a factor of five with decreasing its distance from 40 μm to 0 μm from the auditory neurons. SIGNIFICANCE This study is the first to show electrical activity of SGNs on MEAs. Our findings may help to improve stimulation by and to reduce energy consumption of CIs and thereby contribute to the development of fully implantable devices with better auditory resolution in the future.

Situational adaptiveness of control orientation mediates relation between fixed-world view and youth well-being in three cultures

When proposing primary control (changing the world to fit self)/secondary control (changing self to fit the world) theory, Weisz et al. (1984) argued for the importance of the “serenity to accept the things I cannot change, the courage to change the things I can” (p. 967), and the wisdom to choose the right control strategy that fits the context. Although the dual processes of control theory generated hundreds of empirical studies, most of them focused on the dichotomy of PC and SC, with none of these tapped into the critical concept: individuals’ ability to know when to use what. This project addressed this issue by using scenario questions to study the impact of situationally adaptive control strategies on youth well-being. To understand the antecedents of youths’ preference for PC or SC, we also connected PCSC theory with Dweck’s implicit theory about the changeability of the world. We hypothesized that youths’ belief about the world’s changeability impacts how difficult it was for them to choose situationally adaptive control orientation, which then impacts their well-being. This study included adolescents and emerging adults between the ages of 18 and 28 years (Mean = 20.87 years) from the US (n = 98), China (n = 100), and Switzerland (n = 103). Participants answered a questionnaire including a measure of implicit theories about the fixedness of the external world, a scenario-based measure of control orientation, and several measures of well-being. Preliminary analyses of the scenario-based control orientation measures showed striking cross-cultural similarity of preferred control responses: while for three of the six scenarios primary control was the predominately chosen control response in all cultures, for the other three scenarios secondary control was the predominately chosen response. This suggested that youths across cultures are aware that some situations call for primary control, while others demand secondary control. We considered the control strategy winning the majority of the votes to be the strategy that is situationally adaptive. The results of a multi-group structural equation mediation model with the extent of belief in a fixed world as independent variable, the difficulties of carrying out the respective adaptive versus non-adaptive control responses as two mediating variables and the latent well-being variable as dependent variable showed a cross-culturally similar pattern of effects: a belief in a fixed world was significantly related to higher difficulties in carrying out the normative as well as the non-normative control response, but only the difficulty of carrying out the normative control response (be it primary control in situations where primary control is normative or secondary control in situations where secondary control is normative) was significantly related to a lower reported well-being (while the difficulty of carrying out the non-normative response was unrelated to well-being). While previous research focused on cross-cultural differences on the choice of PC or SC, this study shed light on the universal necessity of applying the right kind of control to fit the situation.

Environmental control on the occurrence of high-coercivity magnetic minerals and formation of iron sulfides in a 640 ka sediment sequence from Lake Ohrid (Balkans)

The bulk magnetic mineral record from Lake Ohrid, spanning the past 637 kyr, reflects large-scale shifts in hydrological conditions, and, superimposed, a strong signal of environmental conditions on glacial–interglacial and millennial timescales. A shift in the formation of early diagenetic ferrimagnetic iron sulfides to siderites is observed around 320 ka. This change is probably associated with variable availability of sulfide in the pore water. We propose that sulfate concentrations were significantly higher before  ∼  320 ka, due to either a higher sulfate flux or lower dilution of lake sulfate due to a smaller water volume. Diagenetic iron minerals appear more abundant during glacials, which are generally characterized by higher Fe / Ca ratios in the sediments. While in the lower part of the core the ferrimagnetic sulfide signal overprints the primary detrital magnetic signal, the upper part of the core is dominated by variable proportions of high- to low-coercivity iron oxides. Glacial sediments are characterized by high concentration of high-coercivity magnetic minerals (hematite, goethite), which relate to enhanced erosion of soils that had formed during preceding interglacials. Superimposed on the glacial–interglacial behavior are millennial-scale oscillations in the magnetic mineral composition that parallel variations in summer insolation. Like the processes on glacial–interglacial timescales, low summer insolation and a retreat in vegetation resulted in enhanced erosion of soil material. Our study highlights that rock-magnetic studies, in concert with geochemical and sedimentological investigations, provide a multi-level contribution to environmental reconstructions, since the magnetic properties can mirror both environmental conditions on land and intra-lake processes.

Automatic quality control in clinical (1) H MRSI of brain cancer.

MRSI grids frequently show spectra with poor quality, mainly because of the high sensitivity of MRS to field inhomogeneities. These poor quality spectra are prone to quantification and/or interpretation errors that can have a significant impact on the clinical use of spectroscopic data. Therefore, quality control of the spectra should always precede their clinical use. When performed manually, quality assessment of MRSI spectra is not only a tedious and time-consuming task, but is also affected by human subjectivity. Consequently, automatic, fast and reliable methods for spectral quality assessment are of utmost interest. In this article, we present a new random forest-based method for automatic quality assessment of (1) H MRSI brain spectra, which uses a new set of MRS signal features. The random forest classifier was trained on spectra from 40 MRSI grids that were classified as acceptable or non-acceptable by two expert spectroscopists. To account for the effects of intra-rater reliability, each spectrum was rated for quality three times by each rater. The automatic method classified these spectra with an area under the curve (AUC) of 0.976. Furthermore, in the subset of spectra containing only the cases that were classified every time in the same way by the spectroscopists, an AUC of 0.998 was obtained. Feature importance for the classification was also evaluated. Frequency domain skewness and kurtosis, as well as time domain signal-to-noise ratios (SNRs) in the ranges 50-75 ms and 75-100 ms, were the most important features. Given that the method is able to assess a whole MRSI grid faster than a spectroscopist (approximately 3 s versus approximately 3 min), and without loss of accuracy (agreement between classifier trained with just one session and any of the other labelling sessions, 89.88%; agreement between any two labelling sessions, 89.03%), the authors suggest its implementation in the clinical routine. The method presented in this article was implemented in jMRUI's SpectrIm plugin. Copyright © 2016 John Wiley & Sons, Ltd.

A qualitative assessment of multi-level nutrition strategies for reducing racial and ethnic disparities in diabetes

The purpose of this study is to examine the stages of program realization of the interventions that the Bronx Health REACH program initiated at various levels to improve nutrition as a means for reducing racial and ethnic disparities in diabetes. This study was based on secondary analyses of qualitative data collected through the Bronx Health REACH Nutrition Project, a project conducted under the auspices of the Institute on Urban Family Health, with support from the Centers for Disease Control and Prevention (CDC). Local human subjects' review and approval through the Institute on Urban Family Health was required and obtained in order to conduct the Bronx Health REACH Nutrition Project. ^ The study drew from two theoretical models—Glanz and colleagues' nutrition environments model and Shediac-Rizkallah and Bone's sustainability model. The specific study objectives were two-fold: (1) to categorize each nutrition activity to a specific dimension (i.e. consumer, organizational or community nutrition environment); and (2) to evaluate the stage at which the program has been realized (i.e. development, implementation or sustainability). ^ A case study approach was applied and a constant comparative method was used to analyze the data. Triangulation of data based was also conducted. Qualitative data from this study revealed the following principal findings: (1) communities of color are disproportionately experiencing numerous individual and environmental factors contributing to the disparities in diabetes; (2) multi-level strategies that targeted the individual, organizational and community nutrition environments can appropriately address these contributing factors; (3) the nutrition strategies greatly varied in their ability to appropriately meet criteria for the three program stages; and (4) those nutrition strategies most likely to succeed (a) conveyed consistent and culturally relevant messages, (b) had continued involvement from program staff and partners, (c) were able to adapt over time or setting, (d) had a program champion and a training component, (e) were integrated into partnering organizations, and (f) were perceived to be successful by program staff and partners in their efforts to create individual, organizational and community/policy change. As a result of the criteria-based assessment and qualitative findings, an ecological framework elaborating on Glanz and colleagues model was developed. The qualitative findings and the resulting ecological framework developed from this study will help public health professionals and community leaders to develop and implement sustainable multi-level nutrition strategies for addressing racial and ethnic disparities in diabetes. ^