2,419 research outputs found
P16-08. Combined blockade of the PD-1 and IL-10 pathways synergistically enhance HIV-specific CD4 T cell functions
Segregation discovery in a social network of companies
We introduce a framework for a data-driven analysis of segregation
of minority groups in social networks, and challenge it on a complex
scenario. The framework builds on quantitative measures of segregation,
called segregation indexes, proposed in the social science literature.
The segregation discovery problem consists of searching sub-graphs and
sub-groups for which a reference segregation index is above a minimum
threshold. A search algorithm is devised that solves the segregation problem.
The framework is challenged on the analysis of segregation of social
groups in the boards of directors of the real and large network of Italian
companies connected through shared directors
Reconciling the optimal and empirical approaches to modelling stomatal conductance
Models of vegetation function are widely used to predict the effects of climate change on carbon, water and nutrient cycles of terrestrial ecosystems, and their feedbacks to climate. Stomatal conductance, the process that governs plant water use and carbon uptake, is fundamental to such models. In this paper, we reconcile two long-standing theories of stomatal conductance. The empirical approach, which is most commonly used in vegetation models, is phenomenological, based on experimental observations of stomatal behaviour in response to environmental conditions. The optimal approach is based on the theoretical argument that stomata should act to minimize the amount of water used per unit carbon gained. We reconcile these two approaches by showing that the theory of optimal stomatal conductance can be used to derive a model of stomatal conductance that is closely analogous to the empirical models. Consequently, we obtain a unified stomatal model which has a similar form to existing empirical models, but which now provides a theoretical interpretation for model parameter values. The key model parameter, g1, is predicted to increase with growth temperature and with the marginal water cost of carbon gain. The new model is fitted to a range of datasets ranging from tropical to boreal trees. The parameter g1 is shown to vary with growth temperature, as predicted, and also with plant functional type. The model is shown to correctly capture responses of stomatal conductance to changing atmospheric CO2, and thus can be used to test for stomatal acclimation to elevated CO2. The reconciliation of the optimal and empirical approaches to modelling stomatal conductance is important for global change biology because it provides a simple theoretical framework for analyzing, and simulating, the coupling between carbon and water cycles under environmental change. © 2011 Blackwell Publishing Ltd
Foot kinematics in patients with two patterns of pathological plantar hyperkeratosis
Background: The Root paradigm of foot function continues to underpin the majority of clinical foot biomechanics practice and foot orthotic therapy. There are great number of assumptions in this popular paradigm, most of which have not been thoroughly tested. One component supposes that patterns of plantar pressure and associated hyperkeratosis lesions should be associated with distinct rearfoot, mid foot, first metatarsal and hallux kinematic patterns. Our aim was to investigate the extent to which this was true.
Methods: Twenty-seven subjects with planter pathological hyperkeratosis were recruited into one of two groups.
Group 1 displayed pathological plantar hyperkeratosis only under metatarsal heads 2, 3 and 4 (n = 14). Group 2
displayed pathological plantar hyperkeratosis only under the 1st and 5th metatarsal heads (n = 13). Foot kinematics
were measured using reflective markers on the leg, heel, midfoot, first metatarsal and hallux.
Results: The kinematic data failed to identify distinct differences between these two groups of subjects, however
there were several subtle (generally <3°) differences in kinematic data between these groups. Group 1 displayed a
less everted heel, a less abducted heel and a more plantarflexed heel compared to group 2, which is contrary to
the Root paradigm.
Conclusions: There was some evidence of small differences between planter pathological hyperkeratosis groups.
Nevertheless, there was too much similarity between the kinematic data displayed in each group to classify them
as distinct foot types as the current clinical paradigm proposes
Neuroactive steroids in depression and anxiety disorders: Clinical studies
Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3 alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3 alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment, we studied the impact of nonpharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation, nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder, changes in neuroactive steroid composition have been observed opposite to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3 alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(A) receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds. Copyright (c) 2006 S. Karger AG, Basel
One-sided versus two-sided stochastic descriptions
It is well-known that discrete-time finite-state Markov Chains, which are
described by one-sided conditional probabilities which describe a dependence on
the past as only dependent on the present, can also be described as
one-dimensional Markov Fields, that is, nearest-neighbour Gibbs measures for
finite-spin models, which are described by two-sided conditional probabilities.
In such Markov Fields the time interpretation of past and future is being
replaced by the space interpretation of an interior volume, surrounded by an
exterior to the left and to the right.
If we relax the Markov requirement to weak dependence, that is, continuous
dependence, either on the past (generalising the Markov-Chain description) or
on the external configuration (generalising the Markov-Field description), it
turns out this equivalence breaks down, and neither class contains the other.
In one direction this result has been known for a few years, in the opposite
direction a counterexample was found recently. Our counterexample is based on
the phenomenon of entropic repulsion in long-range Ising (or "Dyson") models.Comment: 13 pages, Contribution for "Statistical Mechanics of Classical and
Disordered Systems
Childhood bullying, paranoid thinking, and the misappraisal of social threat: trouble at school
Background:Experiences of bullying predict the development of paranoia in school-age adolescents. While many instances of psychotic phenomena are transitory, maintained victimization can lead to increasingly distressing paranoid thinking. Furthermore, paranoid thinkers perceive threat in neutral social stimuli and are vigilant for environmental risk.
Aims:The present paper investigated the association between different forms of bullying and paranoid thinking, and the extent to which school-age paranoid thinkers overestimate threat in interpersonal situations.
Methods: Two hundred and thirty participants, aged between eleven and fourteen, were recruited from one secondary school in the UK. Participants completed a series of questionnaires hosted on the Bristol Online Survey tool. All data were collected in a classroom setting in quiet and standardized conditions.
Results: A significant and positive relationship was found between experiences of bullying and paranoid thinking: greater severity of bullying predicted more distressing paranoid thinking. Further, paranoid thinking mediated the relationship between bullying and overestimation of threat in neutral social stimuli.
Conclusion: Exposure to bullying is associated with distressing paranoid thinking and subsequent misappraisal of threat. As paranoid thinkers experience real and overestimated threat, the phenomena may persist
Mesoscopic organization reveals the constraints governing C. elegans nervous system
One of the biggest challenges in biology is to understand how activity at the
cellular level of neurons, as a result of their mutual interactions, leads to
the observed behavior of an organism responding to a variety of environmental
stimuli. Investigating the intermediate or mesoscopic level of organization in
the nervous system is a vital step towards understanding how the integration of
micro-level dynamics results in macro-level functioning. In this paper, we have
considered the somatic nervous system of the nematode Caenorhabditis elegans,
for which the entire neuronal connectivity diagram is known. We focus on the
organization of the system into modules, i.e., neuronal groups having
relatively higher connection density compared to that of the overall network.
We show that this mesoscopic feature cannot be explained exclusively in terms
of considerations, such as optimizing for resource constraints (viz., total
wiring cost) and communication efficiency (i.e., network path length).
Comparison with other complex networks designed for efficient transport (of
signals or resources) implies that neuronal networks form a distinct class.
This suggests that the principal function of the network, viz., processing of
sensory information resulting in appropriate motor response, may be playing a
vital role in determining the connection topology. Using modular spectral
analysis, we make explicit the intimate relation between function and structure
in the nervous system. This is further brought out by identifying functionally
critical neurons purely on the basis of patterns of intra- and inter-modular
connections. Our study reveals how the design of the nervous system reflects
several constraints, including its key functional role as a processor of
information.Comment: Published version, Minor modifications, 16 pages, 9 figure
Early postural blood pressure response and cause-specific mortality among middle-aged adults
Orthostatic hypotension (OH) is associated with increased total mortality but contribution of specific death causes has not been thoroughly explored. In this prospective study, authors followed up 32,068 individuals without baseline history of cancer or cardiovascular disease (69% men; mean age, 46 years; range, 26–61 years) over a period of 24 years. Hazard ratios (HRs) for total and cause-specific mortality associated with presence of OH and by quartiles of postural systolic blood pressure response (∆SBP) were assessed using multivariate adjusted Cox regression model. A total of 7,145 deaths (22.3%, 9.4 deaths/1,000 person-years) occurred during follow-up. Those with OH (n = 1,943) had higher risk of death due to injury (HR, 1.88; 1.37–2.57) and neurological disease (HR, 2.21; 1.39–3.51). Analogically, risk of death caused by injury and neurological disease increased across the quartiles of ∆SBP from hyper- (Q1SBP, +8.5 ± 4.7 mmHg) to hypotensive response (Q4SBP, −13.7 ± 5.7 mmHg; HR, 1.32; 1.00–1.72, and 1.84; 1.20–2.82, respectively) as did also risk of death due to respiratory disease (Q4SBP vs. Q1SBP: HR, 1.53; 1.14–2.04). In contrast, risk curve for cerebrovascular death was U-shaped with nadir in the mildly hypotensive 3rd quartile of ∆SBP (−5.0 ± 0.1 mmHg, Q3SBP vs. Q1SBP: HR, 0.75; 0.54–1.03; P for linear trend = 0.021). Additionally, cardiovascular mortality was increased among 5,805 rescreened participants (mean age, 53 years; 9.8% OH positive: HR, 1.54; 1.24–1.89, and Q4SBP vs. Q1SBP: 1.27; 1.02–1.57, respectively). In summary, increased mortality predicted by blood pressure fall on standing is associated with injuries, neurodegenerative, and respiratory diseases, as well as with cardiovascular disease in older adults. Moreover, both increase and pronounced decrease of SBP during early orthostasis indicate higher risk of cerebrovascular death
Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients
Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular
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