166 research outputs found
Studying the effects of thalamic interneurons in a thalamocortical neural mass model
Neural mass models of the thalamocortical circuitry are
often used to mimic brain activity during sleep and
wakefulness as observed in scalp electroencephalogram
(EEG) signals [1]. It is understood that alpha rhythms
(8-13 Hz) dominate the EEG power-spectra in the resting-state
[2] as well as the period immediately before
sleep [3]. Literature review shows that the thalamic
interneurons (IN) are often ignored in thalamocortical
population models; the emphasis is on the connections
between the thalamo cortical relay (TCR) and the thalamic
reticular nucleus (TRN). In this work, we look into
the effects of the IN cell population on the behaviour of
an existing thalamocortical model containing the TCR
and TRN cell populations [4]. A schematic of the
extended model used in this work is shown in Fig.1.
The model equations are solved in Matlab using the
Runge-Kutta method of the 4th/5th order. The model
shows high sensitivity to the forward and reverse rates
of reactions during synaptic transmission as well as on
the membrane conductance of the cell populations. The
input to the model is a white noise signal simulating
conditions of resting state with eyes closed, a condition
well known to be associated with dominant alpha band
oscillations in EEG e.g. [5]. Thus, the model parameters
are calibrated to obtain a set of basal parameter values
when the model oscillates with a dominant frequency
within the alpha band. The time series plots and the
power spectra of the model output are compared with
those when the IN cell population is disconnected from
the circuit (by setting the inhibitory connectivity parameter
from the IN to the TCR to zero). We observe
(Fig. 2 inset) a significant difference in time series output
of the TRN cell population with and without the IN
cell population in the model; this in spite of the IN
having no direct connectivity to and from the TRN cell
population (Fig. 1). A comparison of the power spectra
behaviour of the model output within the delta
(1-3.5Hz), theta (3.75-7.5Hz), alpha (7.75-13.5Hz) and
beta (13.75-30.5Hz) bands is shown in Fig. 2. Disconnecting
the IN cell population shows a significant drop in the
alpha band power and the dominant frequency of oscillation
now lies within the theta band. An overall ‘slowing’
(left-side shift) of the power spectra is observed with an
increase within the delta and theta bands and a decrease
in the alpha and beta bands. Such a slowing of EEG is a
signature of slow wave sleep in healthy individuals, and
this suggests that the IN cell population may be centrally
involved in the phase transition to slow wave sleep [6]. It
is also characteristic of the waking EEG in Alzheimer’s
disease, and may help us to understand the role of the IN
cell population in modulating TCR and TRN cell behaviour
in pathological brain conditions
Multi-level selection and the issue of environmental homogeneity
In this paper, I identify two general positions with respect to the relationship between environment and natural selection. These positions consist in claiming that selective claims need and, respectively, need not be relativized to homogenous environments. I then show that adopting one or the other position makes a difference with respect to the way in which the effects of selection are to be measured in certain cases in which the focal population is distributed over heterogeneous environments. Moreover, I show that these two positions lead to two different interpretations – the Pricean and contextualist ones – of a type of selection scenarios in which multiple groups varying in properties affect the change in the metapopulation mean of individual-level traits. Showing that these two interpretations stem from different attitudes towards environmental homogeneity allows me to argue: a) that, unlike the Pricean interpretation, the contextualist interpretation can only claim that drift or selection is responsible for the change in frequency of the focal trait in a given metapopulation if details about whether or not group formation is random are specified; b) that the traditional main objection against the Pricean interpretation – consisting in arguing that the latter takes certain side-effects of individual selection to be effects of group selection – is unconvincing. This leads me to suggest that the ongoing debate about which of the two interpretations is preferable should concentrate on different issues than previously thought
Cumulative readings of every do not provide evidence for events and thematic roles
An argument by Kratzer (2000) based on Schein (1986, 1993) does not conclusively show that events and thematic roles are necessary ingredients of the logical representation of natural language sentences. The argument claims that cumulative readings of every can be represented only with these ingredients. But scope-splitting accounts make it possible to represent cumulative readings of every in an eventless framework. Such accounts are motivated by obligatory reconstruction effects of every and by crosslinguistic considerations. Kratzer proposes that agent but not theme occurs in the logical representation of sentences because this allows her to model subject-object asymmetries in the distribution of cumulative every. But the reason for these asymmetries seems to be that every must be c-commanded by another quantifier in order to cumulate with it, no matter what its thematic role is. So the distribution of cumulative every does not provide support for Kratzer’s proposal
Mass Mortality of Adult Male Subantarctic Fur Seals: Are Alien Mice the Culprits?
Background: Mass mortalities of marine mammals due to infectious agents are increasingly reported. However, in contrast to previous die-offs, which were indiscriminate with respect to sex and age, here we report a land-based mass mortality of Subantarctic fur seals with apparent exclusivity to adult males. An infectious agent with a male-predilection is the most plausible explanation for this die-off. Although pathogens with gender-biased transmission and pathologies are unusual, rodents are known sources of male-biased infectious agents and the invasive Mus musculus house mouse, occurs in seal rookeries. Methodology / Principal Findings: Molecular screening for male-biased pathogens in this potential rodent reservoir host revealed the absence of Cardiovirus and Leptospirosis genomes in heart and kidney samples, respectively, but identified a novel Streptococcus species with 30 % prevalence in mouse kidneys. Conclusions / Significance: Inter-species transmission through environmental contamination with this novel bacterium, whose congenerics display male-bias and have links to infirmity in seals and terrestrial mammals (including humans)
External representations and scientific understanding
This paper provides an inferentialist account of model-based understanding by combining a counterfactual account of explanation and an inferentialist account of representation with a view of modeling as extended cognition. This account makes it understandable how the manipulation of surrogate systems like models can provide genuinely new empirical understanding about the world. Similarly, the account pro- vides an answer to the question how models, that always incorporate assumptions that are literally untrue of the model target, can still provide factive explanations. Finally, the paper shows how the contrastive counterfactual theory of explanation can provide tools for assessing the explanatory power of models.Peer reviewe
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
BACKGROUND:
Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.
METHODS:
We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.
RESULTS:
During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.
CONCLUSIONS:
Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)
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