437 research outputs found
Free will and the search for happiness
En este trabajo, inspirados por la mentalidad agustiniana,
trataremos el libre albedrío como medio necesario para lograr la felicidad.
Tras unas reflexiones generales sobre la mente, el libre albedrío y
la felicidad, hablaremos acerca del libre albedrío como requisito para la
felicidad y nos centraremos en el libertarismo. Los partidarios de esta
corriente sostienen que el libre albedrío existe pero es incompatible con
el determinismo, de modo que requiere alguna clase de indeterminismo.
Esto trae consigo un problema de inteligibilidad: ¿acaso el indeterminismo
no conlleva aleatoriedad y, como consecuencia, carencia de
control sobre lo que decidimos y hacemos? Sin embargo, describiremos
dos propuestas libertaristas que tratan de dar una explicación inteligible al papel que desempeña el indeterminismo en el ejercicio de nuestro
libre albedrío. La primera propuesta, que es ampliamente conocida internacionalmente,
es la de Robert Kane. La segunda ha sido defendida
por Carlos Moya, el más importante pensador libertarista dentro del
ámbito hispano.In this work we will deal with free will as a necessary
means to achieve happiness, inspired by the Augustinian mentality. After
some general reflections on mind, free will and happiness, we will
address free will as a requirement for happiness and will focus on libertarianism.
The advocates for this trend argue that free will exists but is
incompatible with determinism, so it requires some kind of indeterminism.
This poses a problem of intelligibility: does not indeterminism entail
randomness and, consequently, lack of control over what we decide
and do? However, we will describe two libertarian proposals that try to
give an intelligible explanation to the role played by indeterminism in
the exercise of our free will. The first proposal, which is widely known
internationally, is that of Robert Kane. The second has been defended
by Carlos Moya, the most important libertarian thinker within the Hispanic
sphere.Filosofí
A study of the pressure profiles near the first pumping aperture in a high pressure photoelectron spectrometer
The origin and collapse of rock glaciers during the Bølling-Allerød interstadial: A new study case from the Cantabrian Mountains (Spain)
.During the Late Pleistocene, the main mountain ranges of the Iberian Peninsula were covered by small icefields and cirque and alpine glaciers. The deglaciation triggered paraglacial processes that generated landforms, mostly within the ice-free glacial cirques. In this research we analyse the deglaciation process in the Muxivén Cirque (42°15′N – 6°16′W), in the upper Sil River Basin, which includes some of the largest relict rock glaciers of the Cantabrian Mountains. We addressed this objective by means of accurate geomorphological reconstructions, sedimentological analysis, Schmidt-hammer surface weathering measurements and a dataset of 10 10Be Cosmic-Ray Exposure ages. Results reveal that after ~16 ka, glaciers retreated to the bottom of the cirques at the headwaters of the valley, leaving the walls free of ice and triggering rock avalanches onto the remnants of these glaciers. This paraglacial process supplied debris to a small glacier within Muxivén Cirque, which transformed in two rock glaciers. These debris isolated the ice inside the rock glaciers only for a very short period of time and ended up melting completely before the Younger Dryas. The lower sector of the largest one stabilized at 14.5 ± 1.5 ka, while the upper sector remained active until 13.5 ± 0.8 ka. Previous to the stabilization of the lower sector of the northern rock glacier, at its margin a high-energy debris avalanche occurred at ~14.0 ± 0.9 ka. These data agree with previous research, corroborating the paraglacial origin of most Iberian rock glaciers during the Bølling-Allerød interstadial.S
Bevacizumab Diminishes Inflammation in an Acute Endotoxin-Induced Uveitis Model
Introduction: Uveitis is an eye disease characterized by inflammation of the uvea and an early and exhaustive diagnosis is essential for its treatment. The aim of our study is to assess the potential toxicity and anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model by subcutaneously injecting lipopolysaccharide into Lewis rats and to clarify its mechanism.Material and Methods: Blood–aqueous barrier integrity was assessed 24 h after endotoxin-induced uveitis (EIU) by analyzing two parameters: cell count and protein concentration in aqueous humors. Histopathology of all eye structures was also studied. Enzyme-linked immunosorbent analyses of the aqueous humor samples were performed in order to calculate the diverse chemokine and cytokine protein levels and oxidative stress-related markers were also evaluated.Results: The aqueous humor’s cellular content significantly increased in the group treated with only Bevacizumab, but it had no effect on retina histopathological grading. Nevertheless, the inflammation noted in ocular structures when administering Bevacizumab with endotoxin was mostly prevented since aqueous humor cell content considerably lowered, and concomitantly with a sharp drop in uveal, vitreous, and retina histopathological grading. The values of the multi-faceted cytokine IL-2 also significantly decreased (p < 0.05 vs. endotoxin group), and the protective IL-6 and IL-10 cytokines values rose with related anti-oxidant system recovery (p < 0.05 vs. endotoxin group). Concurrently, some related M1 macrophage chemokines substantially increased, e.g., GRO/KC, a chemokine that also displays any kind of protective role.Conclusion: All these results revealed that 24 h after being administered, Bevacizumab treatment in EIU significantly prevented inflammation in various eye structures and correct results in efficacy vs. toxicity balance were obtained
Spatial Regulation of Membrane Fusion Controlled by Modification of Phosphoinositides
Membrane fusion plays a central role in many cell processes from vesicular
transport to nuclear envelope reconstitution at mitosis but the mechanisms that
underlie fusion of natural membranes are not well understood. Studies with
synthetic membranes and theoretical considerations indicate that accumulation of
lipids characterised by negative curvature such as diacylglycerol (DAG)
facilitate fusion. However, the specific role of lipids in membrane fusion of
natural membranes is not well established. Nuclear envelope (NE) assembly was
used as a model for membrane fusion. A natural membrane population highly
enriched in the enzyme and substrate needed to produce DAG has been isolated and
is required for fusions leading to nuclear envelope formation, although it
contributes only a small amount of the membrane eventually incorporated into the
NE. It was postulated to initiate and regulate membrane fusion. Here we use a
multidisciplinary approach including subcellular membrane purification,
fluorescence spectroscopy and Förster resonance energy transfer
(FRET)/two-photon fluorescence lifetime imaging microscopy (FLIM) to demonstrate
that initiation of vesicle fusion arises from two unique sites where these
vesicles bind to chromatin. Fusion is subsequently propagated to the endoplasmic
reticulum-derived membranes that make up the bulk of the NE to ultimately
enclose the chromatin. We show how initiation of multiple vesicle fusions can be
controlled by localised production of DAG and propagated bidirectionally.
Phospholipase C (PLCγ), GTP hydrolysis and
(phosphatidylinsositol-(4,5)-bisphosphate (PtdIns(4,5)P2) are
required for the latter process. We discuss the general implications of membrane
fusion regulation and spatial control utilising such a mechanism
Adequate antibiotic therapy prior to ICU admission in patients with severe sepsis and septic shock reduces hospital mortality
Genomic Insights Into The Ixodes scapularis Tick Vector Of Lyme Disease
Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retrotransposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing B57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing’, prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent
Genomic Insights Into The Ixodes scapularis Tick Vector Of Lyme Disease
Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retrotransposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing B57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing’, prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent
Positive End-Expiratory Pressure may alter breathing cardiovascular variability and baroreflex gain in mechanically ventilated patients
<p>Abstract</p> <p>Background</p> <p>Baroreflex allows to reduce sudden rises or falls of arterial pressure through parallel RR interval fluctuations induced by autonomic nervous system. During spontaneous breathing, the application of positive end-expiratory pressure (PEEP) may affect the autonomic nervous system, as suggested by changes in baroreflex efficiency and RR variability. During mechanical ventilation, some patients have stable cardiorespiratory phase difference and high-frequency amplitude of RR variability (HF-RR amplitude) over time and others do not. Our first hypothesis was that a steady pattern could be associated with reduced baroreflex sensitivity and HF-RR amplitude, reflecting a blunted autonomic nervous function. Our second hypothesis was that PEEP, widely used in critical care patients, could affect their autonomic function, promoting both steady pattern and reduced baroreflex sensitivity.</p> <p>Methods</p> <p>We tested the effect of increasing PEEP from 5 to 10 cm H2O on the breathing variability of arterial pressure and RR intervals, and on the baroreflex. Invasive arterial pressure, ECG and ventilatory flow were recorded in 23 mechanically ventilated patients during 15 minutes for both PEEP levels. HF amplitude of RR and systolic blood pressure (SBP) time series and HF phase differences between RR, SBP and ventilatory signals were continuously computed by complex demodulation. Cross-spectral analysis was used to assess the coherence and gain functions between RR and SBP, yielding baroreflex-sensitivity indices.</p> <p>Results</p> <p>At PEEP 10, the 12 patients with a stable pattern had lower baroreflex gain and HF-RR amplitude of variability than the 11 other patients. Increasing PEEP was generally associated with a decreased baroreflex gain and a greater stability of HF-RR amplitude and cardiorespiratory phase difference. Four patients who exhibited a variable pattern at PEEP 5 became stable at PEEP 10. At PEEP 10, a stable pattern was associated with higher organ failure score and catecholamine dosage.</p> <p>Conclusions</p> <p>During mechanical ventilation, stable HF-RR amplitude and cardiorespiratory phase difference over time reflect a blunted autonomic nervous function which might worsen as PEEP increases.</p
Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial
Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals
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