216 research outputs found
Decoding Rich Spatial Information with High Temporal Resolution
New research suggests that magnetoencephalography (MEG) contains rich spatial information for decoding neural states. Even small differences in the angle of neighbouring dipoles generate subtle, but statistically separable field patterns. This implies MEG (and electroencephalography: EEG) is ideal for decoding neural states with high-temporal resolution in the human brain
Intrinsic neuronal dynamics predict distinct functional roles during working memory
Working memory (WM) is characterized by the ability to maintain stable representations over time; however, neural activity associated with WM maintenance can be highly dynamic. We explore whether complex population coding dynamics during WM relate to the intrinsic temporal properties of single neurons in lateral prefrontal cortex (lPFC), the frontal eye fields (FEF), and lateral intraparietal cortex (LIP) of two monkeys (Macaca mulatta). We find that cells with short timescales carry memory information relatively early during memory encoding in lPFC; whereas long-timescale cells play a greater role later during processing, dominating coding in the delay period. We also observe a link between functional connectivity at rest and the intrinsic timescale in FEF and LIP. Our results indicate that individual differences in the temporal processing capacity predict complex neuronal dynamics during WM, ranging from rapid dynamic encoding of stimuli to slower, but stable, maintenance of mnemonic information.Biotechnology and Biological Sciences Research Council (Great Britain) (BB/M010732/1)United States. Office of Naval Research (N00014-14-1-0681)National Institute of Mental Health (U.S.) (R00MH092715)National Institute of Mental Health (U.S.) (R37MH087027)Massachusetts Institute of Technology. Picower Innovation FundUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (grant N00014-16-1-2832)National Institute for Health Research (Great Britain). Wellcome Trust (203139/Z/16/Z
Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations-State-of-the-Art.
Cancer and COVID-19 are both well-established risk factors predisposing to
thrombosis. Both disease entities are correlated with increased incidence of
venous thrombotic events through multifaceted pathogenic mechanisms involving
the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation
system and endothelial cells on the other hand. Thromboprophylaxis is
recommended for hospitalized patients with active cancer and high-risk
outpatients with cancer receiving anticancer treatment. Universal
thromboprophylaxis with a high prophylactic dose of low molecular weight
heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated
for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is
recommended for outpatients with COVID-19 at high risk for thrombosis or disease
worsening. However, whether there is an additive risk of thrombosis when a
patient with cancer is infected with SARS-CoV2 remains unclear In the current
review, we summarize and critically discuss the literature regarding the
epidemiology of thrombotic events in patients with cancer and concomitant
COVID-19, the thrombotic risk assessment, and the recommendations on
thromboprophylaxis for this subgroup of patients. Current data do not support an
additive thrombotic risk for patients with cancer and COVID-19. Of note,
patients with cancer have less access to intensive care unit care, a setting
associated with high thrombotic risk. Based on current evidence, patients with
cancer and COVID-19 should be assessed with well-established risk assessment
models for medically ill patients and receive thromboprophylaxis, preferentially
with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist
Drafting a composite indicator of validity for regulatory models and legal systems
The aim of this paper is to lay the groundwork for the creation of a composite indicator of the validity of regulatory systems. The composite nature of the indicator implies a) that its construction is embedded in the long-standing theoretical debate and framework of legal validity; b) that it formally contains other sub-indicators whose occurrence is essential to the determination of validity. The paper suggests, in other words, that validity is a second-degree property, i.e., one that occurs only once the justice, efficiency, effectiveness, and enforceability of the system have been checked
Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis
Background: Sympathetic tone is one of the main
determinants of blood pressure (BP) variability and
treatment-resistant hypertension. The aim of our study was
to assess changes in BP variability after renal denervation
(RDN). In addition, on an exploratory basis, we investigated
whether baseline BP variability predicted the BP changes
after RDN.
Methods: We analyzed 24-h BP recordings obtained at
baseline and 6 months after RDN in 167 treatmentresistant
hypertension patients (40% women; age, 56.7
years; mean 24-h BP, 152/90 mmHg) recruited at 11 expert
centers. BP variability was assessed by weighted SD [SD
over time weighted for the time interval between
consecutive readings (SDiw)], average real variability (ARV),
coefficient of variation, and variability independent of the
mean (VIM).
Results: Mean office and 24-h BP fell by 15.4/6.6 and 5.5/
3.7 mmHg, respectively (P < 0.001). In multivariable-adjusted
analyses, systolic/diastolic SDiw and VIM for 24-h
SBP/DBP decreased by 1.18/0.63 mmHg (P 0.01) and
0.86/0.42 mmHg (P 0.05), respectively, whereas no
significant changes in ARV or coefficient of variation
occurred. Furthermore, baseline SDiw (P ¼ 0.0006), ARV
(P ¼ 0.01), and VIM (P ¼ 0.04) predicted the decrease in
24-h DBP but not 24-h SBP after RDN.
Conclusion: RDN was associated with a decrease in BP
variability independent of the BP level, suggesting that
responders may derive benefits from the reduction in BP
variability as well. Furthermore, baseline DBP variability
estimates significantly correlated with mean DBP decrease
after RDN. If confirmed in younger patients with less
arterial damage, in the absence of the confounding effect
of drugs and drug adherence, baseline BP variability may
prove a good predictor of BP response to RDN
Digital multiplex ligation assay for highly multiplexed screening of beta-lactamase-encoding genes in bacterial isolates
Increasing incidence of antibiotic resistance in clinical and environmental settings calls for increased scalability in their surveillance. Current screening technologies are limited by the number of samples and genes that can easily be screened. We demonstrate here digital multiplex ligation assay (dMLA) as a low-cost targeted genomic detection workflow capable of highly-parallel screening of bacterial isolates for multiple target gene regions simultaneously. Here, dMLA is used for simultaneous detection of 1187 beta-lactamase-encoding genes, including extended spectrum beta-lactamase (ESBL) genes, in 74 bacterial isolates. We demonstrate dMLA as a light-weight and cost-efficient workflow which provides a highly scalable tool for antimicrobial resistance surveillance and is also adaptable to genetic screening applications beyond antibiotic resistance.Tamminen et al. develop a digital multiplex ligation assay (dMLA) that enables the detection of bacterial isolates using probe hybridization and ligation-based assays with next-generation sequencing. Their method can be applied in high-throughput and affordable screening for antibiotic resistance
Differential Levels of Stress Proteins (HSPs) in Male and Female Daphnia magna in Response to Thermal Stress: A Consequence of Sex-Related Behavioral Differences?
In two independent experiments, we compared: (1) water depth selection (and accompanying temperature selection) by male and female Daphnia magna under different kinds of environmental stress, including the presence of filamentous cyanobacteria, the risk of predation from fish, and the presence of toxic compounds; and (2) sex-dependent production of heat shock proteins (HSP60, 70, and 90) in response to a sudden change in temperature. Male D. magna selected deep water strata, which offer a relatively stable environment, and thereby avoided the threat of predation and the presence of toxic compounds in surface waters. Correlated with this behavior, males reduce their molecular defenses against stress, such as the production of heat shock proteins (HSPs), and do not maintain the physiological machinery that triggers an increase in HSP levels in response to stress. In contrast, female D. magna actively select habitats that offer optimal conditions for growth and production of offspring. Consequently, females are exposed to variable environmental conditions that may be associated with increased stress. To permit survival in these different habitats, D. magna females require molecular mechanisms to protect their cells from rapid changes in stress levels. Thus, they maintain high constitutive levels of the heat shock proteins from HSP 60, 70, and 90 families, and they have the potential to further enhance the production of the majority of these proteins under stress conditions. The results of this study indicate that the separate habitats selected by male and female D. magna result in different patterns of HSP production, leading us to hypothesize that that male and female Daphnia magna adopt different strategies to maximize the fitness of the species
Effects of juvenile host density and food availability on adult immune response, parasite resistance and virulence in a Daphnia-parasite system
Host density can increase infection rates and reduce host fitness as increasing population density enhances the risk of becoming infected either through increased encounter rate or because host condition may decline. Conceivably, potential hosts could take high host density as a cue to up-regulate their defence systems. However, as host density usually covaries with food availability, it is difficult to examine the importance of host density in isolation. Thus, we performed two full-factorial experiments that varied juvenile densities of Daphnia magna (a freshwater crustacean) and food availability independently. We also included a simulated high-density treatment, where juvenile experimental animals were kept in filtered media that previously maintained Daphnia at high-density. Upon reaching adulthood, we exposed the Daphnia to their sterilizing bacterial parasite, Pasteuria ramosa, and examined how the juvenile treatments influenced the likelihood and severity of infection (Experiment I) and host immune investment (Experiment II). Neither juvenile density nor food treatments affected the likelihood of infection; however, well-fed hosts that were well-fed as juveniles produced more offspring prior to sterilization than their less well-fed counterparts. By contrast, parasite growth was independent of host juvenile resources or host density. Parasite-exposed hosts had a greater number of circulating haemocytes than controls (i.e., there was a cellular immune response), but the magnitude of immune response was not mediated by food availability or host density. These results suggest that density dependent effects on disease arise primarily through correlated changes in food availability: low food could limit parasitism and potentially curtail epidemics by reducing both the host's and parasite's reproduction as both depend on the same food
Strong differences in the clonal variation of two Daphnia species from mountain lakes affected by overwintering strategy
<p>Abstract</p> <p>Background</p> <p>The population structure of cyclical parthenogens such as water fleas is strongly influenced by the frequency of alternations between sexual and asexual (parthenogenetic) reproduction, which may differ among populations and species. We studied genetic variation within six populations of two closely related species of water fleas of the genus <it>Daphnia </it>(Crustacea, Cladocera). <it>D. galeata </it>and <it>D. longispina </it>both occur in lakes in the Tatra Mountains (Central Europe), but their populations show distinct life history strategies in that region. In three studied lakes inhabited by <it>D. galeata</it>, daphnids overwinter under the ice as adult females. In contrast, in lakes inhabited by <it>D. longispina</it>, populations apparently disappear from the water column and overwinter as dormant eggs in lake sediments. We investigated to what extent these different strategies lead to differences in the clonal composition of late summer populations.</p> <p>Results</p> <p>Analysis of genetic variation at nine microsatellite loci revealed that clonal richness (expressed as the proportion of different multilocus genotypes, MLGs, in the whole analysed sample) consistently differed between the two studied species. In the three <it>D. longispina </it>populations, very high clonal richness was found (MLG/N ranging from 0.97 to 1.00), whereas in <it>D. galeata </it>it was much lower (0.05 to 0.50). The dominant MLGs in all <it>D. galeata </it>populations were heterozygous at five or more loci, suggesting that such individuals all represented the same clonal lineages rather than insufficiently resolved groups of different clones.</p> <p>Conclusions</p> <p>The low clonal diversities and significant deviations from Hardy-Weinberg equilibrium in <it>D. galeata </it>populations were likely a consequence of strong clonal erosion over extended periods of time (several years or even decades) and the limited influence of sexual reproduction. Our data reveal that populations of closely related <it>Daphnia </it>species living in relatively similar habitats (permanent, oligotrophic mountain lakes) within the same region may show strikingly different genetic structures, which most likely depend on their reproductive strategy during unfavourable periods. We assume that similar impacts of life history on population structures are also relevant for other cyclical parthenogen groups. In extreme cases, prolonged clonal erosion may result in the dominance of a single clone within a population, which might limit its microevolutionary potential if selection pressures suddenly change.</p
To whom does the law speak? Canvassing a neglected picture of law’s interpretive field
Among the most common strategies underlying the so-called indeterminacy thesis is the following two-step argument: (1) that law is an interpretive practice, and that evidently legal actors more generally hold different (and competing) theories of meaning, which lead to disagreements as to what the law says (that is, as to what the law is); (2) and that, as there is no way to establish the prevalence of one particular theory of meaning over the other, indeterminacy is pervasive in law. In this paper I offer some reflections to resist this trend. In particular I claim that a proper understanding of law as an authoritative communicative enterprise sheds new light on the relation between the functioning of the law and our theories of interpretation, leading to what can be considered a neglected conclusion: the centrality of the linguistic criterion of meaning in our juridical interpretive practices. In the first part of the chapter I discuss speech-act theory in the study of law, assessing its relevance between alternative options. Then I tackle the ‘to whom does the law speak?’ question, highlighting the centrality of lay-people for our juridical practices. Lastly, I examine the consequences of this neglected fact for our interpretive theories
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