Functional neuroimaging of emotional learning and autonomic reactions

This article provides a selective overview of the functional neuroimaging literature with an emphasis on emotional activation processes. Emotions are fast and flexible response systems that provide basic tendencies for adaptive action. From the range of involved component functions, we first discuss selected automatic mechanisms that control basic adaptational changes. Second, we illustrate how neuroimaging work has contributed to the mapping of the network components associated with basic emotion families (fear, anger, disgust, happiness), and secondary dimensional concepts that organise the meaning space for subjective experience and verbal labels (emotional valence, activity/intensity, approach/withdrawal, etc.). Third, results and methodological difficulties are discussed in view of own neuroimaging experiments that investigated the component functions involved in emotional learning. The amygdala, prefrontal cortex, and striatum form a network of reciprocal connections that show topographically distinct patterns of activity as a correlate of up and down regulation processes during an emotional episode. Emotional modulations of other brain systems have attracted recent research interests. Emotional neuroimaging calls for more representative designs that highlight the modulatory influences of regulation strategies and socio-cultural factors responsible for inhibitory control and extinction. We conclude by emphasising the relevance of the temporal process dynamics of emotional activations that may provide improved prediction of individual differences in emotionality.

Tracking the subprocesses of decision-based action in the human frontal lobes

Situationally adaptive behavior relies on the identification of relevant target stimuli, the evaluation of these with respect to the current context and the selection of an appropriate action. We used functional magnetic resonance imaging (fMRI) to disentangle the neural networks underlying these processes within a single task. Our results show that activation of mid-ventrolateral prefrontal cortex (PFC) reflects the perceived presence of a target stimulus regardless of context, whereas context-appropriate evaluation is subserved by mid-dorsolateral PFC. Enhancing demands on response selection by means of response conflict activated a network of regions, all of which are directly connected to motor areas. On the midline, rostral anterior paracingulate cortex was found to link target detection and response selection by monitoring for the presence of behaviorally significant conditions. In summary, we provide new evidence for process-specific functional dissociations in the frontal lobes. In target-centered processing, target detection in the VLPFC is separable from contextual evaluation in the DLPFC. Response-centered processing in motor-associated regions occurs partly in parallel to these processes, which may enhance behavioral efficiency, but it may also lead to reaction time increases when an irrelevant response tendency is elicited.

Learning real-world stimuli in a neural network with spike-driven synaptic dynamics

We present a model of spike-driven synaptic plasticity inspired by experimental observations and motivated by the desire to build an electronic hardware device that can learn to classify complex stimuli in a semisupervised fashion. During training, patterns of activity are sequentially imposed on the input neurons, and an additional instructor signal drives the output neurons toward the desired activity. The network is made of integrate-and-fire neurons with constant leak and a floor. The synapses are bistable, and they are modified by the arrival of presynaptic spikes. The sign of the change is determined by both the depolarization and the state of a variable that integrates the postsynaptic action potentials. Following the training phase, the instructor signal is removed, and the output neurons are driven purely by the activity of the input neurons weighted by the plastic synapses. In the absence of stimulation, the synapses preserve their internal state indefinitely. Memories are also very robust to the disruptive action of spontaneous activity. A network of 2000 input neurons is shown to be able to classify correctly a large number (thousands) of highly overlapping patterns (300 classes of preprocessed Latex characters, 30 patterns per class, and a subset of the NIST characters data set) and to generalize with performances that are better than or comparable to those of artificial neural networks. Finally we show that the synaptic dynamics is compatible with many of the experimental observations on the induction of long-term modifications (spike-timing-dependent plasticity and its dependence on both the postsynaptic depolarization and the frequency of pre- and postsynaptic neurons).

Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies

BACKGROUND: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. METHODS: We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. FINDINGS: We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. INTERPRETATION: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.

Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991-2000

Candida species are among the most common bloodstream pathogens in the United States, where the emergence of azole-resistant Candida glabrata and Candida krusei are major concerns. Recent comprehensive longitudinal data from Europe are lacking. We conducted a nationwide survey of candidemia during 1991-2000 in 17 university and university-affiliated hospitals representing 79% of all tertiary care hospital beds in Switzerland. The number of transplantations and bloodstream infections increased significantly (P<.001). A total of 1137 episodes of candidemia were observed: Candida species ranked seventh among etiologic agents (2.9% of all bloodstream isolates). The incidence of candidemia was stable over a 10-year period. C. albicans remained the predominant Candida species recovered (66%), followed by C. glabrata (15%). Candida tropicalis emerged (9%), the incidence of Candida parapsilosis decreased (1%), and recovery of C. krusei remained rare (2%). Fluconazole consumption increased significantly (P<.001). Despite increasing high-risk activities, the incidence of candidemia remained unchanged, and no shift to resistant species occurred.

Oxidized low density lipoprotein impairs endothelial progenitor cell function by downregulation of E-selectin and integrin alpha(v)beta5

BACKGROUND: Oxidized low density lipoprotein (oxLDL) has been shown to induce apoptosis and senescence of endothelial progenitor cells (EPC). In the present study, we hypothesized that even sub-apoptotic concentrations of oxLDL impair the angiogenic potential of EPC and investigated if this effect is mediated by affecting adhesion and incorporation. METHODS: A co-culture system of human microvascular endothelial cells and EPC was used to study the effect of sub-apoptotic concentrations of native (nLDL) and oxLDL on cell-cell interaction. The expression and the functional role of angiogenic adhesion molecules and integrins was monitored by FACS and neutralizing assay, respectively. RESULTS: We observed an inhibition of tube formation and impairment of EPC integration into the vascular network of mature endothelial cells by oxLDL. In contrast, nLDL did not affect angiogenic properties of EPC. Incubation of EPC with sub-apoptotic oxLDL concentrations significantly decreased E-selectin and integrin alpha(v)beta(5) expression (37.6% positive events vs. 71.5% and 24.3% vs. 49.9% compared to control culture media without oxLDL). Interestingly, expression of alpha(v)beta(3), VE-cadherin and CD31 remained unchanged. Blocking of E-selectin and integrin alpha(v)beta(5) by neutralizing antibody effectively inhibited adhesion of EPC to differentiated endothelial cells (56.5% and 41.9% of control; p<0.001). CONCLUSION: In conclusion, oxidative alteration of LDL impairs angiogenic properties of EPC at sub-apoptotic levels by downregulation of E-selectin and integrin alpha(v)beta(5), both substantial mediators of EPC-endothelial cell interaction.

Hydrologic monitoring of an integrated low impact development (LID) underdrained stormwater management system

In 2005, Wetland Studies and Solutions, Inc. (WSSI) installed an extensive Low Impact Development (LID) stormwater management system on their new office site in Gainesville, Virginia. The 4-acre site is serviced by a network of LID components: permeable pavements (two proprietary and one gravel type), bioretention cell / rain garden, green roof, vegetated swale, rainwater harvesting and drip irrigation, and slow-release underground detention. The site consists of heavy clay soils, and the LID components are mostly integrated by a series of underdrain pipes. A comprehensive monitoring system has been designed and installed to measure hydrologic performance throughout the LID, underdrained network. The monitoring system measures flows into and out of each LID component independently while concurrently monitoring rainfall events. A sensitivity analysis and laboratory calibration has been performed on the flow measurement system. Field data has been evaluated to determine the hydrologic performance of the LID features. Finally, hydrologic models amenable to compact, underdrained LID sites have been reviewed and recommended for future modeling and design.

Gender and the use of antiretroviral treatment in resource-constrained settings: findings from a multicenter collaboration

AIMS: To compare the gender distribution of HIV-infected adults receiving highly active antiretroviral treatment (HAART) in resource-constrained settings with estimates of the gender distribution of HIV infection; to describe the clinical characteristics of women and men receiving HAART. METHODS: The Antiretroviral Therapy in Lower-Income Countries, ART-LINC Collaboration is a network of clinics providing HAART in Africa, Latin America, and Asia. We compared UNAIDS data on the gender distribution of HIV infection with the proportions of women and men receiving HAART in the ART-LINC Collaboration. RESULTS: Twenty-nine centers in 13 countries participated. Among 33,164 individuals, 19,989 (60.3%) were women. Proportions of women receiving HAART in ART-LINC centers were similar to, or higher than, UNAIDS estimates of the proportions of HIV-infected women in all but two centers. There were fewer women receiving HAART than expected from UNAIDS data in one center in Uganda and one center in India. Taking into account heterogeneity across cohorts, women were younger than men, less likely to have advanced HIV infection, and more likely to be anemic at HAART initiation. CONCLUSIONS: Women in resource-constrained settings are not necessarily disadvantaged in their access to HAART. More attention needs to be paid to ensuring that HIV-infected men are seeking care and starting HAART.

Modeling mechanical response of heterogeneous materials

Heterogeneous materials are ubiquitous in nature and as synthetic materials. These materials provide unique combination of desirable mechanical properties emerging from its heterogeneities at different length scales. Future structural and technological applications will require the development of advanced light weight materials with superior strength and toughness. Cost effective design of the advanced high performance synthetic materials by tailoring their microstructure is the challenge facing the materials design community. Prior knowledge of structure-property relationships for these materials is imperative for optimal design. Thus, understanding such relationships for heterogeneous materials is of primary interest. Furthermore, computational burden is becoming critical concern in several areas of heterogeneous materials design. Therefore, computationally efficient and accurate predictive tools are highly essential. In the present study, we mainly focus on mechanical behavior of soft cellular materials and tough biological material such as mussel byssus thread. Cellular materials exhibit microstructural heterogeneity by interconnected network of same material phase. However, mussel byssus thread comprises of two distinct material phases. A robust numerical framework is developed to investigate the micromechanisms behind the macroscopic response of both of these materials. Using this framework, effect of microstuctural parameters has been addressed on the stress state of cellular specimens during split Hopkinson pressure bar test. A voronoi tessellation based algorithm has been developed to simulate the cellular microstructure. Micromechanisms (microinertia, microbuckling and microbending) governing macroscopic behavior of cellular solids are investigated thoroughly with respect to various microstructural and loading parameters. To understand the origin of high toughness of mussel byssus thread, a Genetic Algorithm (GA) based optimization framework has been developed. It is found that two different material phases (collagens) of mussel byssus thread are optimally distributed along the thread. These applications demonstrate that the presence of heterogeneity in the system demands high computational resources for simulation and modeling. Thus, Higher Dimensional Model Representation (HDMR) based surrogate modeling concept has been proposed to reduce computational complexity. The applicability of such methodology has been demonstrated in failure envelope construction and in multiscale finite element techniques. It is observed that surrogate based model can capture the behavior of complex material systems with sufficient accuracy. The computational algorithms presented in this thesis will further pave the way for accurate prediction of macroscopic deformation behavior of various class of advanced materials from their measurable microstructural features at a reasonable computational cost.

Measures of endothelial dysfunction in plasma of patients with posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) confers an increased cardiovascular risk. In 14 otherwise healthy patients with PTSD and in 14 age- and gender-matched non-PTSD controls, we investigated whether the categorical diagnosis of PTSD and severity of PTSD symptom clusters (i.e. re-experiencing, avoidance, arousal, and overall score) would be associated with plasma concentrations of three markers of endothelial dysfunction [soluble tissue factor (sTF), von Willebrand factor (VWF), and soluble intercellular adhesion molecule (sICAM)-1]. Compared with controls, patients had significantly higher sTF; this difference became nonsignificant when controlling for psychological distress. VWF and sICAM-1 levels were not significantly different between patients and controls. In the entire sample virtually all PTSD symptom clusters correlated significantly and positively with sTF and VWF but not with sICAM-1. The correlation between symptoms of re-experiencing and sTF was significantly different between patients and controls. Controlling for symptoms of anxiety and depression (i.e. psychological distress) rendered most associations between PTSD symptom clusters and sTF nonsignificant, whereas controlling for age retained significance of associations with VWF. Posttraumatic stress showed a continuous relationship with sTF and VWF, with the former relationship being partly affected by psychological distress. This suggests one mechanism by which posttraumatic stress could contribute to atherosclerosis.

The Problematic of Privacy in the Namespace

In the twenty-first century, the issue of privacy--particularly the privacy of individuals with regard to their personal information and effects--has become highly contested terrain, producing a crisis that affects both national and global social formations. This crisis, or problematic, characterizes a particular historical conjuncture I term the namespace. Using cultural studies and the theory of articulation, I map the emergent ways that the namespace articulates economic, juridical, political, cultural, and technological forces, materials, practices and protocols. The cohesive articulation of the namespace requires that privacy be reframed in ways that make its diminution seem natural and inevitable. In the popular media, privacy is often depicted as the price we pay as citizens and consumers for security and convenience, respectively. This discursive ideological shift supports and underwrites the interests of state and corporate actors who leverage the ubiquitous network of digitally connected devices to engender a new regime of informational surveillance, or dataveillance. The widespread practice of dataveillance represents a strengthening of the hegemonic relations between these actors--each shares an interest in promoting an emerging surveillance society, a burgeoning security politics, and a growing information economy--that further empowers them to capture and store the personal information of citizens/consumers. In characterizing these shifts and the resulting crisis, I also identify points of articulation vulnerable to rearticulation and suggest strategies for transforming the namespace in ways that might empower stronger protections for privacy and related civil rights.

Evaluation of sugar maple dieback in the Upper Great Lakes region and development of a forest health youth education program

Acer saccharum Marsh., is one of the most valuable trees in the northern hardwood forests. Severe dieback was recently reported by area foresters in the western Upper Great Lakes Region. Sugar Maple has had a history of dieback over the last 100 years throughout its range and different variables have been identified as being the predisposing and inciting factors in different regions at different times. Some of the most common factors attributed to previous maple dieback episodes were insect defoliation outbreaks, inadequate precipitation, poor soils, atmospheric deposition, fungal pathogens, poor management, or a combination of these. The current sugar maple dieback was evaluated to determine the etiology, severity, and change in dieback on both industry and public lands. A network of 120 sugar maple health evaluation plots was established in the Upper Peninsula, Michigan, northern Wisconsin, and eastern Minnesota and evaluated annually from 2009-2012. Mean sugar maple crown dieback between 2009-2012 was 12.4% (ranging from 0.8-75.5%) across the region. Overall, during the sampling period, mean dieback decreased by 5% but individual plots and trees continued to decline. Relationships were examined between sugar maple dieback and growth, habitat conditions, ownership, climate, soil, foliage nutrients, and the maple pathogen sapstreak. The only statistically significant factor was found to be a high level of forest floor impacts due to exotic earthworm activity. Sugar maple on soils with lower pH had less earthworm impacts, less dieback, and higher growth rates than those on soils more favorable to earthworms. Nutritional status of foliage and soil was correlated with dieback and growth suggesting perturbation of nutrient cycling may be predisposing or contributing to dieback. The previous winter's snowfall totals, length of stay on the ground, and number of days with freezing temperatures had a significant positive relationship to sugar maple growth rates. Sapstreak disease, Ceratocystis virescens, may be contributing to dieback in some stands but was not related to the amount of dieback in the region. The ultimate goal of this research is to help forest managers in the Great Lakes Region prevent, anticipate, reduce, and/or salvage stands with dieback and loss in the future. An improved understanding of the complex etiology associated with sugar maple dieback in the Upper Great Lakes Region is necessary to make appropriate silvicultural decisions. Forest Health education helps increase awareness and proactive forest management in the face of changing forest ecosystems. Lessons are included to assist educators in incorporating forest health into standard biological disciplines at the secondary school curricula.

AccessMod 3.0: computing geographic coverage and accessibility to health care services using anisotropic movement of patients

Background Access to health care can be described along four dimensions: geographic accessibility, availability, financial accessibility and acceptability. Geographic accessibility measures how physically accessible resources are for the population, while availability reflects what resources are available and in what amount. Combining these two types of measure into a single index provides a measure of geographic (or spatial) coverage, which is an important measure for assessing the degree of accessibility of a health care network. Results This paper describes the latest version of AccessMod, an extension to the Geographical Information System ArcView 3.×, and provides an example of application of this tool. AccessMod 3 allows one to compute geographic coverage to health care using terrain information and population distribution. Four major types of analysis are available in AccessMod: (1) modeling the coverage of catchment areas linked to an existing health facility network based on travel time, to provide a measure of physical accessibility to health care; (2) modeling geographic coverage according to the availability of services; (3) projecting the coverage of a scaling-up of an existing network; (4) providing information for cost effectiveness analysis when little information about the existing network is available. In addition to integrating travelling time, population distribution and the population coverage capacity specific to each health facility in the network, AccessMod can incorporate the influence of landscape components (e.g. topography, river and road networks, vegetation) that impact travelling time to and from facilities. Topographical constraints can be taken into account through an anisotropic analysis that considers the direction of movement. We provide an example of the application of AccessMod in the southern part of Malawi that shows the influences of the landscape constraints and of the modes of transportation on geographic coverage. Conclusion By incorporating the demand (population) and the supply (capacities of heath care centers), AccessMod provides a unifying tool to efficiently assess the geographic coverage of a network of health care facilities. This tool should be of particular interest to developing countries that have a relatively good geographic information on population distribution, terrain, and health facility locations.

Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD database and the GALEN platform. The Galenda project

Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments.

Structural characterization and reliable biomechanical assessment of integrative cartilage repair

Structural and functional characterization of integrative cartilage repair in controlled model systems can play a key role in the development of innovative strategies to improve the long-term outcome of many cartilage repair procedures. In this work, we first developed a method to reproducibly generate geometrically defined disk/ring cartilage composites and to remove outgrown fibrous layers which can encapsulate cartilaginous tissues during culture. We then used the model system to test the hypothesis that such fibrous layers lead to an overestimation of biomechanical parameters of integration at the disk/ring interface. Transmission electron microscopy images of the composites after 6 weeks of culture indicated that collagen fibrils in the fibrous tissue layer were well integrated into the collagen network of the cartilage disk and ring, whereas molecular bridging between opposing disk/ring cartilage surfaces was less pronounced and restricted to regions with narrow interfacial regions (< 2 microm). Stress-strain profiles generated from mechanical push-out tests for composites with the layers removed displayed a single and distinct peak, whereas profiles for composites with the layers left intact consisted of multiple superimposed peaks. As compared to composites with removed layers, composites with intact layers had significantly higher adhesive strengths (161+/-9 vs. 71+/-11 kPa) and adhesion energies (15.0+/-0.7 vs. 2.7+/-0.4 mJ/mm2). By combining structural and functional analyses, we demonstrated that the outgrowing tissue formed during in vitro culture of cartilaginous specimens should be eliminated in order to reliably quantify biomechanical parameters related to integrative cartilage repair.