BDNF Val66Met polymorphism influence on striatal blood-level-dependent response to monetary feedback depends on valence and agency

Animal work implicates the brain-derived neurotrophic factor (BDNF) in function of the ventral striatum (VS), a region known for its role in processing valenced feedback. Recent evidence in humans shows that BDNF Val66Met polymorphism modulates VS activity in anticipation of monetary feedback. However, it remains unclear whether the polymorphism impacts the processing of self-attributed feedback differently from feedback attributed to an external agent. In this study, we emphasize the importance of the feedback attribution because agency is central to computational accounts of the striatum and cognitive accounts of valence processing. We used functional magnetic resonance imaging and a task, in which financial gains/losses are either attributable to performance (self-attributed, SA) or chance (externally-attributed, EA) to ask whether BDNF Val66Met polymorphism predicts VS activity. We found that BDNF Val66Met polymorphism influenced how feedback valence and agency information were combined in the VS and in the right inferior frontal junction (IFJ). Specifically, Met carriers' VS response to valenced feedback depended on agency information, while Val/Val carriers' VS response did not. This context-specific modulation of valence effectively amplified VS responses to SA losses in Met carriers. The IFJ response to SA losses also differentiated Val/Val from Met carriers. These results may point to a reduced allocation of attention and altered motivational salience to SA losses in Val/Val compared to Met carriers. Implications for major depressive disorder are discussed.

Fully automatic segmentation of AP pelvis X-rays via random forest regression with efficient feature selection and hierarchical sparse shape composition

In clinical practice, traditional X-ray radiography is widely used, and knowledge of landmarks and contours in anteroposterior (AP) pelvis X-rays is invaluable for computer aided diagnosis, hip surgery planning and image-guided interventions. This paper presents a fully automatic approach for landmark detection and shape segmentation of both pelvis and femur in conventional AP X-ray images. Our approach is based on the framework of landmark detection via Random Forest (RF) regression and shape regularization via hierarchical sparse shape composition. We propose a visual feature FL-HoG (Flexible- Level Histogram of Oriented Gradients) and a feature selection algorithm based on trace radio optimization to improve the robustness and the efficacy of RF-based landmark detection. The landmark detection result is then used in a hierarchical sparse shape composition framework for shape regularization. Finally, the extracted shape contour is fine-tuned by a post-processing step based on low level image features. The experimental results demonstrate that our feature selection algorithm reduces the feature dimension in a factor of 40 and improves both training and test efficiency. Further experiments conducted on 436 clinical AP pelvis X-rays show that our approach achieves an average point-to-curve error around 1.2 mm for femur and 1.9 mm for pelvis.

Holistic patterns as an instrument to predict promising young football players

Multidimensional talent models represent the current state of the art. However, it remains unclear how these different dimensions interact. Based on current theories of human development, person-oriented approaches seem to be particularly appropriate for talent research. The present study adopts this approach by looking at how a holistic system consisting of the dimensions motivation, motor behaviour and the stage of development goes along with athletic performance. For this purpose, it has to be examined which patterns were formed by the constructs net hope, motor abilities, technical skills and the so far achieved percentage of the predicted adult height and how these patterns are related to subsequent sporting success. 119 young elite football players were questioned and tested three times at intervals of one year, beginning at the age of 12. At the age of 15, the performance level the players had reached was examined. At all three measuring points, four patterns were identified which displayed partial structural and high individual stability. As expected, the players showing values above average in all factors were significantly more likely to advance to the highest performance level. Physically strong, precocious developed players though having some technical weaknesses, have good chances to reach the middle performance level. The results point to the importance of holistic approaches for the prediction of performance among promising football talents in the medium-term and thus provide valuable clues for their selection and promotion.

Holistic patterns as an instrument to predict performance of promising young football players

Multidimensional talent models represent the current state of the art. However, it remains unclear how these different dimensions interact. Based on current theories of human development, person-oriented approaches seem to be particularly appropriate for talent research. The present study adopts this approach by looking at how a holistic system consisting of the different dimensions motivation, motor behaviour and the stage of development goes along with athletic performance. For this purpose, it has to be examined which patterns were formed by the constructs net hope (Elbe et al., 2003), motor abilities (3 motor tests; Höner et al., 2014), technical skills (3 motor tests; Höner et al., 2014) and the so far achieved percentage of the predicted adult height (Mirwald et al, 2002) and how these patterns are related to subsequent sporting success. 119 young elite football players were questioned and tested three times at intervals of one year, beginning at the age of 12. At the age of 15, the performance level the players had reached was examined (national, regional or no talent card). At all three measuring points, four patterns were identified which displayed partial structural and high individual stability. As expected, the players showing values above average in all factors were significantly more likely to advance to the highest performance level (Odds ratio = 2.2, p < .01). Physically strong, precocious developed players though having some technical weaknesses, have good chances to reach the middle performance level (OR = 1.6, p = .01). Players showing values under average, have an one and a half times higher probability to advance to the lowest performance level (p < .01). The results point to the importance of holistic approaches for the prediction of performance among promising football talents in the medium-term and thus provide valuable clues for their selection and promotion.

Itineraries of pottery: a mixed methods approach to mobility

Neolithic wetland sites in the Swiss Plateau provide an extraordinary database for the study of mobilities, entanglements and transformations in material culture. Based on dendrochronologically dated settlements between 3900 and 3500 BC, two regional pottery styles and their local variations are well known, Pfyn and Cortaillod. The vessels share the same habitus and were made of local raw materials. However, some vessels specific to other pottery styles are also present in the sites. By focusing on itineraries of vessels and shifts in pottery knowledge, their appropriation in different contexts and the resulting material entanglements, we want to approach the multiple regimes of mobility: At Lake Constance - known for Pfyn pottery - specific Michelsberg vessels like tulip beakers and lugged jars occur in small numbers. These travelling objects were produced with exogenous raw materials and transported to the sites from Southern Germany. At Concise (Lake Neuchâtel) besides the local Cortaillod pottery the whole repertoire of NMB pottery, characteristic for Eastern France, was also produced. Further cases from the same space-time frame point to other regimes of mobility. In our two PhD-projects we compare pottery practices - styles, techniques, raw materials - from over 20 key sites in the region. Based on Bourdieu’s reflexive anthropology, we apply different qualitative and quantitative archaeological and archaeometrical methods, thus striving for a deeper understanding of habitus and the transformative potential of moving people, objects and ideas on local and regional scales and related social contexts.

Treatment allocation in hepatocellular carcinoma: Assessment of the BCLC algorithm

BACKGROUND AND AIMS The Barcelona Clinic Liver Cancer (BCLC) staging system is the algorithm most widely used to manage patients with hepatocellular carcinoma (HCC). We aimed to investigate the extent to which the BCLC recommendations effectively guide clinical practice and assess the reasons for any deviation from the recommendations. MATERIAL AND METHODS The first-line treatments assigned to patients included in the prospective Bern HCC cohort were analyzed. RESULTS Among 223 patients included in the cohort, 116 were not treated according to the BCLC algorithm. Eighty percent of the patients in BCLC stage 0 (very early HCC) and 60% of the patients in BCLC stage A (early HCC) received recommended curative treatment. Only 29% of the BCLC stage B patients (intermediate HCC) and 33% of the BCLC stage C patients (advanced HCC) were treated according to the algorithm. Eighty-nine percent of the BCLC stage D patients (terminal HCC) were treated with best supportive care, as recommended. In 98 patients (44%) the performance status was disregarded in the stage assignment. CONCLUSION The management of HCC in clinical practice frequently deviates from the BCLC recommendations. Most of the curative therapy options, which have well-defined selection criteria, were allocated according to the recommendations, while the majority of the palliative therapy options were assigned to patients with tumor stages not aligned with the recommendations. The only parameter which is subjective in the algorithm, the performance status, is also the least respected.

Immune regulatory and neuroprotective properties of preimplantation factor: From newborn to adult.

Embryonic-maternal interaction from the earliest stages of gestation has a key, sustained role in neurologic development, persisting into adulthood. Early adverse events may be detrimental in adulthood. Protective factors present during gestation could significantly impact post-natal therapy. The role of PreImplantation Factor (PIF) within this context is herein examined. Secreted by viable early embryos, PIF establishes effective embryonic-maternal communication and exerts essential trophic and protective roles by reducing oxidative stress and protein misfolding and by blunting the nocive let-7 microRNA related pathway. PIF's effects on systemic immunity lead to comprehensive immune modulation, not immune suppression. We examine PIF's role in protecting embryos from adverse maternal environment, which can lead to neurological disorders that may only manifest post-nataly: Synthetic PIF successfully translates endogenous PIF features in both pregnant and non-pregnant clinically relevant models. Specifically PIF has neuroprotective effects in neonatal prematurity. In adult relapsing-remitting neuroinflammation, PIF reverses advanced paralysis while promoting neurogenesis. PIF reversed Mycobacterium smegmatis induced brain infection. In graft-vs.-host disease, PIF reduced skin ulceration, liver inflammation and colon ulceration while maintaining beneficial anti-cancer, graft-vs.-leukemia effect. Clinical-grade PIF has high-safety profile even at supraphysiological doses. The FDA awarded Fast-Track designation, and university-sponsored clinical trials for autoimmune disorder are ongoing. Altogether, PIF properties point to its determining regulatory role in immunity, inflammation and transplant acceptance. Specific plans for using PIF for the treatment of complex neurological disorders (ie. traumatic brain injury, progressive paralysis), including neuroprotection from newborn to adult, are presented.

SOP: Parallel surrogate global optimization with Pareto center selection for computationally expensive single objective problems

This paper presents a parallel surrogate-based global optimization method for computationally expensive objective functions that is more effective for larger numbers of processors. To reach this goal, we integrated concepts from multi-objective optimization and tabu search into, single objective, surrogate optimization. Our proposed derivative-free algorithm, called SOP, uses non-dominated sorting of points for which the expensive function has been previously evaluated. The two objectives are the expensive function value of the point and the minimum distance of the point to previously evaluated points. Based on the results of non-dominated sorting, P points from the sorted fronts are selected as centers from which many candidate points are generated by random perturbations. Based on surrogate approximation, the best candidate point is subsequently selected for expensive evaluation for each of the P centers, with simultaneous computation on P processors. Centers that previously did not generate good solutions are tabu with a given tenure. We show almost sure convergence of this algorithm under some conditions. The performance of SOP is compared with two RBF based methods. The test results show that SOP is an efficient method that can reduce time required to find a good near optimal solution. In a number of cases the efficiency of SOP is so good that SOP with 8 processors found an accurate answer in less wall-clock time than the other algorithms did with 32 processors.

Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling

Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth.

A program manual to assist with implementation of a volunteer health and wellness program

Based on the success of a community health and wellness program, Wellness in the City, delivered in Dallas County by trained volunteers, Texas Cooperative Extension (TCE) decided to pilot the program in 16 counties in North and East Texas. Before implementing the program, TCE wanted the Dallas County program to be reviewed and revised as needed to meet the diverse community needs in the pilot counties. TCE also asked for an implementation manual to be developed for the county agents to utilize. ^ To achieve these objectives, I first reviewed literature on other volunteer-implemented health interventions in the U.S. to see how they were planned, disseminated, implemented, and evaluated. Next, I reviewed the Wellness in the City program and materials. I applied all the information I gathered up to that point to the program development committee meetings (committee included seven TCE county agents, a TCE regional program director, and me). The program structure and training materials were revised based on our research and program implementation experience. These changes were made to ensure adequate training for the volunteers and to create a program that is applicable in the communities it will be piloted in. ^ With the program structure and training presentations developed, next I focused on compiling the implementation manual, which includes program details and volunteer recruitment, training, and management materials. The goal was to create a manual with everything the county agents will need to implement the program, so they can focus their efforts on putting the manual to use and recruiting and managing the volunteers. The final step was developing a program evaluation form for the agents to complete. It includes questions to assess the agents' thoughts about the training content, the feasibility of implementing the program using the manual, and the challenges of the program. ^

Diagnosis of sexually transmitted infections in developing nations using syndromic management: Is it working?

Sexually transmitted infections (STIs) are a major public health problem, and controlling their spread is a priority. According to the World Health Organization (WHO), there are 340 million new cases of treatable STIs among 15–49 year olds that occur yearly around the world (1). Infection with STIs can lead to several complications such as pelvic inflammatory disorder (PID), cervical cancer, infertility, ectopic pregnancy, and even death (1). Additionally, STIs and associated complications are among the top disease types for which healthcare is sought in developing nations (1), and according to the UNAIDS report, there is a strong connection between STIs and the sexual spread of HIV infection (2). In fact, it is estimated that the presence of an untreated STI can increase the likelihood of contracting and spreading HIV by a factor up to 10 (2). In addition, developing countries are poorer in resources and lack inexpensive and precise diagnostic laboratory tests for STIs, thereby exacerbating the problem. Thus, the WHO recommends syndromic management of STIs for delivering care where lab testing is scarce or unattainable (1). This approach utilizes the use of an easy to use algorithm to help healthcare workers recognize symptoms/signs so as to provide treatment for the likely cause of the syndrome. Furthermore, according to the WHO, syndromic management offers instant and legitimate treatment compared to clinical diagnosis, and that it is also more cost-effective for some syndromes over the use of laboratory testing (1). In addition, even though it has been shown that the vaginal discharge syndrome has low specificity for gonorrhea and Chlamydia and can lead to over treatment (1), this is the recommended way to manage STIs in developing nations. Thus, the purpose of this paper is to specifically address the following questions: is syndromic management working to lower the STI burden in developing nations? How effective is it, and should it still be recommended? To answer these questions, a systematic literature review was conducted to evaluate the current effectiveness of syndromic management in developing nations. This review examined published articles over the past 5 years that compared syndromic management to laboratory testing and had published sensitivity, specificity, and positive predicative value data. Focusing mainly on vaginal discharge, urethral discharge, and genital ulcer algorithms, it was seen that though syndromic management is more effective in diagnosing and treating urethral and genial ulcer syndromes in men, there still remains an urgent need to revise the WHO recommendations for managing STIs in developing nations. Current studies have continued to show decreased specificity, sensitivity and positive predicative values for the vaginal discharge syndrome, and high rates of asymptomatic infections and healthcare workers neglecting to follow guidelines limit the usefulness of syndromic management. Furthermore, though advocate d as cost-effective by the WHO, there is a cost incurred from treating uninfected people. Instead of improving this system, it is recommended that better and less expensive point of care and the development of rapid test diagnosis kits be the focus and method of diagnosis and treatment in developing nations for STI management. ^

The diagnostic value of a 12-lead electrocardiogram in patients with cardiac tamponade due to a malignant pericardial effusion

Background. Cardiac tamponade can occur when a large amount of fluid, gas, singly or in combination, accumulating within the pericardium, compresses the heart causing circulatory compromise. Although previous investigators have found the 12-lead ECG to have a poor predictive value in diagnosing cardiac tamponade, very few studies have evaluated it as a follow up tool for ruling in or ruling out tamponade in patients with previously diagnosed malignant pericardial effusions. ^ Methods. 127 patients with malignant pericardial effusions at the MD Anderson Cancer Center were included in this retrospective study. While 83 of these patients had a cardiac tamponade diagnosed by echocardiographic criteria (Gold standard), 44 did not. We computed the sensitivity (Se), specificity (Sp), positive (PPV) and negative predictive values (NPV) for individual and combinations of ECG abnormalities. Individual ECG abnormalities were also entered singly into a univariate logistic regression model to predict tamponade. ^ Results. For patients with effusions of all sizes, electrical alternans had a Se, Sp, PPV and NPV of 22.61%, 97.61%, 95% and 39.25% respectively. These parameters for low voltage complexes were 55.95%, 74.44%, 81.03%, 46.37% respectively. The presence of all three ECG abnormalities had a Se = 8.33%, Sp = 100%, PPV = 100% and NPV = 35.83% while the presence of at least one of the three ECG abnormalities had a Se = 89.28%, Sp = 46.51%, PPV = 76.53%, NPV = 68.96%. For patients with effusions of all sizes electrical alternans had an OR of 12.28 (1.58–95.17, p = 0.016), while the presence of at least one ECG abnormality had an OR of 7.25 (2.9–18.1, p = 0.000) in predicting tamponade. ^ Conclusions. Although individual ECG abnormalities had low sensitivities, specificities, NPVs and PPVs with the exception of electrical alternans, the presence of at least one of the three ECG abnormalities had a high sensitivity in diagnosing cardiac tamponade. This could point to its potential use as a screening test with a correspondingly high NPV to rule out a diagnosis of tamponade in patients with malignant pericardial effusions. This could save expensive echocardiographic assessments in patients with previously diagnosed pericardial effusions. ^

Stable isotopes, sedimentology and geochemical analyses of Middle Eocene to early Miocene sediments of ODP Site 177-1090

During Leg 177 of the Ocean Drilling Program (ODP), a well-preserved middle Eocene to lower Miocene sediment record was recovered at Site 1090 on the Agulhas Ridge in the Atlantic sector of the Southern Ocean. This new sediment record shows evidence of a hitherto unknown late Eocene opal pulse. Lithological variations, compositional data, mass-accumulation rates of biogenic and lithogenic sediment constituents, grain-size distributions, geochemistry, and clay mineralogy are used to gain insights into mid-Cenozoic environmental changes and to explore the circumstances of the late Eocene opal pulse in terms of reorganizations in ocean circulation. The base of the section is composed of middle Eocene nannofossil oozes mixed with red clays enriched in authigenic clinoptilolite and smectite, deposited at low sedimentation rates (LE 2 cm/ka). It indicates reduced terrigenous sediment input and moderate biological productivity during this preglacial warm climatic stage. The basal strata are overlain by an extended succession (100 m, 4 cm/ka) of biosiliceous oozes and muds, comprising the upper middle Eocene, the entire late Eocene, and the lowermost early Oligocene. The opal pulse occurred between 37.5 and 33.5 Ma and documents the development of upwelling cells along topographic highs, and the utilization of a marine nutrient- and silica reservoir established during the pre-late Eocene through enhanced submarine hydrothermal activity and the introduction of terrigenous solutions from chemical weathering on adjacent continents. This palaeoceanographic overturn probably was initiated through the onset of increased meridional ocean circulation, caused by the diversion of the Indian equatorial current to the south. The opal pulse was accompanied by increased influxes of terrigenous detritus from southern African sources (illite), mediated by enhanced ocean particle advection in response to modified ocean circulation. The opal pulse ended because of frontal shifts to the south around the Eocene/Oligocene boundary, possibly in response to the opening of the Drake Passage and the incipient establishment of the Antarctic Circumpolar Current. Condensed sediments and a hiatus within the early Oligocene part of the section possibly point to an invigoration of the deep-reaching Antarctic Circumpolar Current. The mid-Oligocene to lower Miocene section on long time scale exhibits less pronounced lithological variations than the older section and points to relatively stable palaeoceanographic conditions after the dramatic changes in the late Eocene to early Oligocene.

Chemical composition and description of a ferromanganese crust, sample 89D, obtained during R/V Capricorne cruise ARCANTE 1

A manganese oxide encrustation (2.5 kg) was dredged, in an island arc setting, downslope of Bertrand bank, a seamount culminating at 70-m depth and located NNE of Grande-Terre, Guadeloupe, and SE of Antigua, West Indies. A thorough texturai analysis indicated a rhythmic precipitation and growth polarity as well as mineralogical ( 10 A tektomanganate) and geochemical (low concentrations of Ni, Cu, Co, Zn, Pb and REE) criteria, point to a submarine hydrothermal origin for most of the sample. The crust was coated with a fine ferromanganese oxide cortex deposited iii a "normal" oceanic environment; it also included micritic fillings, a main pyroclastic zone near the top of the crust, and a Mg-Al sulphate deposit. Planktonic foraminifera coeval with the precipitation of the manganese oxide indicate an age of ca. 3 m. y. (upper Pliocene); i.e., more than 20 m. y. after the cessation of the volcanic activity of the Lesser Antilles outer arc that was responsible for the buildup of the Bertrand seamount. Furthermore, the genesis of the crust is not linked to the activity of the contemporaneous inner arc (Miocene to Present), particularly of its nearmost segment (Basse Terre, Guadeloupe-Montserrat) located about 50 km to the West. The authors suggest that the manganese oxide is the result of convective circulation of sea water through a faulted system occurring in an area of intense seismic activity. The remobilization of chemical elements (Mn, S, etc.) within the seamount volcanic core bas probably affected a substratum that was still hydrothermally altered during the previous volcanic activity of the outer arc. The authors insist on the interest in using texturai analysis for Fe/Mn oxide investigations.

GLMP for automatic assessment of DFS algorithm learning

We describe how to use a Granular Linguistic Model of a Phenomenon (GLMP) to assess e-learning processes. We apply this technique to evaluate algorithm learning using the GRAPHs learning environment.