1,737 research outputs found
Why I tense up when you watch me: inferior parietal cortex mediates an audienceâs influence on motor performance
The presence of an evaluative audience can alter skilled motor performance through changes in force output. To investigate how this is mediated within the brain, we emulated real-time social monitoring of participantsâ performance of a fine grip task during functional magnetic resonance neuroimaging. We observed an increase in force output during social evaluation that was accompanied by focal reductions in activity within bilateral inferior parietal cortex. Moreover, deactivation of the left inferior parietal cortex predicted both inter- and intra-individual differences in socially-induced change in grip force. Social evaluation also enhanced activation within the posterior superior temporal sulcus, which conveys visual information about othersâ actions to the inferior parietal cortex. Interestingly, functional connectivity between these two regions was attenuated by social evaluation. Our data suggest that social evaluation can vary force output through the altered engagement of inferior parietal cortex; a region implicated in sensorimotor integration necessary for object manipulation, and a component of the action-observation network which integrates and facilitates performance of observed actions. Social-evaluative situations may induce high-level representational incoherence between oneâs own intentioned action and the perceived intention of others which, by uncoupling the dynamics of sensorimotor facilitation, could ultimately perturbe motor output
Reducing broad-spectrum antibiotic use in intensive care unit between first and second waves of COVID-19 did not adversely affect mortality
Background: The COVID-19 pandemic increased the use of broad-spectrum antibiotics due to diagnostic uncertainty, particularly in critical care. Multi-professional communication became more difficult, weakening stewardship activities. Aim: To determine changes in bacterial co-/secondary infections and antibiotics used in COVID-19 patients in critical care, and mortality rates, between the first and second waves. Methods: Prospective audit comparing bacterial co-/secondary infections and their treatment during the first two waves of the pandemic in a single-centre teaching hospital intensive care unit. Data on demographics, daily antibiotic use, clinical outcomes, and culture results in patients diagnosed with COVID-19 infection were collected over 11 months. Findings: From March 9th, 2020 to September 2nd, 2020 (Wave 1), there were 156 patients and between September 3rd, 2020 and February 1st, 2021 (Wave 2) there were 235 patients with COVID-19 infection admitted to intensive care. No significant difference was seen in mortality or positive blood culture rates between the two waves. The proportion of patients receiving antimicrobial therapy (93.0% vs 81.7%; P < 0.01) and the duration of meropenem use (median (interquartile range): 5 (2â7) vs 3 (2â5) days; P = 0.01) was lower in Wave 2. However, the number of patients with respiratory isolates of Pseudomonas aeruginosa (4/156 vs 21/235; P < 0.01) and bacteraemia from a respiratory source (3/156 vs 20/235; P < 0.01) increased in Wave 2, associated with an outbreak of infection. There was no significant difference between waves with respect to isolation of other pathogens. Conclusion: Reduced broad-spectrum antimicrobial use in the second wave of COVID-19 compared with the first wave was not associated with significant change in mortality
Pharmacokinetics and tissue distribution of PGGâpaclitaxel, a novel macromolecular formulation of paclitaxel, in nu/nu mice bearing NCI-460 lung cancer xenografts
PGGâPTX is a water-soluble formulation of paclitaxel (PTX), made by conjugating PTX to poly(l-Îł-glutamylglutamine) acid (PGG) via ester bonds, that spontaneously forms a nanoparticle in aqueous environments. The purpose of this study was to compare the pharmacokinetics and tissue distribution of PTX following injection of either free PTX or PGGâPTX in mice.
Both [3H]PTX and PGGâ[3H]PTX were administered as an IV bolus injection to mice bearing SC NCI-H460 lung cancer xenografts at a dose of 40-mg PTX equivalents/kg. Plasma, tumor, major organs, urine, and feces were collected at intervals out to 340Â h. Total taxanes, taxane extractable into ethyl acetate, and native PTX were quantified by liquid scintillation counting and HPLC.
Conjugation of PTX to the PGG polymer increased plasma and tumor C
max, prolonged plasma half-life and the period of accumulation in tumor, and reduced washout from tumor. In plasma injection of PGGâPTX increased total taxane AUC0â340 by 23-fold above that attained with PTX. In tumors, it increased the total taxane by a factor of 7.7, extractable taxane by 5.7, and native PTX by a factor of 3.5-fold. Conjugation delayed and reduced total urinary and fecal excretion of total taxanes.
Incorporation of PTX into the PGGâPTX polymer significantly prolonged the half-life of total taxanes, extractable taxane, and native PTX in both the plasma and tumor compartments. This resulted in a large increase in the amount of active PTX delivered to the tumor. PGGâPTX is an attractive candidate for further development
Statistical analysis of modal gating in ion channels
Ion channels regulate the concentrations of ions within cells. By stochastically opening and closing its pore, they enable or prevent ions from crossing the cell membrane. However, rather than opening with a constant probability, many ion channels switch between several different levels of activity even if the experimental conditions are unchanged. This phenomenon is known as modal gating: instead of directly adapting its activity, the channel seems to mix sojourns in active and inactive modes in order to exhibit intermediate open probabilities. Evidence is accumulating that modal gating rather than modulation of opening and closing at a faster time scale is the primary regulatory mechanism of ion channels. However, currently, no method is available for reliably calculating sojourns in different modes. In order to address this challenge, we develop a statistical framework for segmenting single-channel datasets into segments that are characteristic for particular modes. The algorithm finds the number of mode changes, detects their locations and infers the open probabilities of the modes. We apply our approach to data from the inositol-trisphosphate receptor. Based upon these results, we propose that mode changes originate from alternative conformational states of the channel protein that determine a certain level of channel activity
Safety of procedural sedation and analgesia in children less than 2 years of age in a pediatric emergency department
Validity of measures of pain and symptoms in HIV/AIDS infected households in resources poor settings: results from the Dominican Republic and Cambodia
BACKGROUND: HIV/AIDS treatment programs are currently being mounted in many developing nations that include palliative care services. While measures of palliative care have been developed and validated for resource rich settings, very little work exists to support an understanding of measurement for Africa, Latin America or Asia. METHODS: This study investigates the construct validity of measures of reported pain, pain control, symptoms and symptom control in areas with high HIV-infected prevalence in Dominican Republic and Cambodia Measures were adapted from the POS (Palliative Outcome Scale). Households were selected through purposive sampling from networks of people living with HIV/AIDS. Consistencies in patterns in the data were tested used Chi Square and Mantel Haenszel tests. RESULTS: The sample persons who reported chronic illness were much more likely to report pain and symptoms compared to those not chronically ill. When controlling for the degrees of pain, pain control did not differ between the chronically ill and non-chronically ill using a Mantel Haenszel test in both countries. Similar results were found for reported symptoms and symptom control for the Dominican Republic. These findings broadly support the construct validity of an adapted version of the POS in these two less developed countries. CONCLUSION: The results of the study suggest that the selected measures can usefully be incorporated into population-based surveys and evaluation tools needed to monitor palliative care and used in settings with high HIV/AIDS prevalence
Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.
OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality
Lethal trap created by adaptive evolutionary response to an exotic resource
International audienceGlobal transport of organisms by humans provides novel resources to wild species, which often respond maladaptively. Native herbivorous insects have been killed feeding on toxic exotic plants, which acted as âecological trapsâ1,2,3,4. We document a novel âeco-evolutionary trapâ stemming from the opposite effect; that is, high fitness on an exotic resource despite lack of adaptation to it. Plantago lanceolata was introduced to western North America by cattle-ranching. Feeding on this exotic plant released a large, isolated population of the native butterfly Euphydryas editha from a longstanding trade-off between maternal fecundity and offspring mortality. Because of this releaseâand despite a reduced insect developmental rate when feeding on this exoticâPlantago immediately supported higher larval survival than did the insectsâ traditional host, Collinsia parviflora5. Previous work from the 1980s documented an evolving preference for Plantago by ovipositing adults6. We predicted that if this trend continued the insects could endanger themselves, because the availability of Plantago to butterflies is controlled by humans, who change land management practices faster than butterflies evolve6. Here we report the fulfilment of this prediction. The butterflies abandoned Collinsia and evolved total dependence on Plantago. The trap was set. In 2005, humans withdrew their cattle, springing the trap. Grasses grew around the Plantago, cooling the thermophilic insects, which then went extinct. This local extinction could have been prevented if the population had retained partial use of Collinsia, which occupied drier microhabitats unaffected by cattle removal. The flush of grasses abated quickly, rendering the meadow once again suitable for Euphydryas feeding on either host, but no butterflies were observed from 2008 to 2012. In 2013â2014, the site was naturally recolonized by Euphydryas feeding exclusively on Collinsia, returning the system to its starting point and setting the stage for a repeat of the anthropogenic evolutionary cycle
Preclinical efficacy studies of a novel nanoparticle-based formulation of paclitaxel that out-performs Abraxane
Poly-(Îł-l-glutamylglutamine)âpaclitaxel (PGGâPTX) is a novel polymer-based formulation of paclitaxel (PTX) in which the PTX is linked to the polymer via ester bonds. PGGâPTX is of interest because it spontaneously forms very small nanoparticles in plasma. In mouse models, PGGâPTX increased tumor exposure to PTX by 7.7-fold relative to that produced by PTX formulated in Cremophor. In this study, the efficacy of PGGâPTX was compared to that of Abraxane, an established nanoparticular formulation of PTX, in three different tumor models.
Efficacy was quantified by delay in tumor growth of NCI H460 human lung cancer, 2008 human ovarian cancer and B16 melanoma xenografts growing in athymic mice following administration of equitoxic doses of PGGâPTX and Abraxane administered on either a single dose or every 7Â day schedule. Toxicity was assessed by change in total body weight.
The efficacy and toxicity of PGGâPTX was shown to increase with dose in the H460 model. PGGâPTX was ~1.5-fold less potent than Abraxane. PGGâPTX produced statistically significantly greater inhibition of tumor growth than Abraxane in all three tumor models when mice were given single equitoxic doses of drug. When given every 7Â days for 3 doses, PGGâPTX produced greater inhibition of tumor growth while generating much less weight loss in mice bearing H460 tumors.
PGGâPTX has activity that is superior to that of Abraxane in multiple tumor models. PGGâPTX has the potential to out-perform Abraxane in enhancing the delivery of PTX tumors while at the same time further reducing the toxicity of both single dose and weekly treatment regimens
Public engagement on global health challenges
<p>Abstract</p> <p>Background</p> <p>Experience with public engagement activities regarding the risks and benefits of science and technology (S&T) is growing, especially in the industrialized world. However, public engagement in the developing world regarding S&T risks and benefits to explore health issues has not been widely explored.</p> <p>Methods</p> <p>This paper gives an overview about public engagement and related concepts, with a particular focus on challenges and benefits in the developing world. We then describe an Internet-based platform, which seeks to both inform and engage youth and the broader public on global water issues and their health impacts. Finally, we outline a possible course for future action to scale up this and similar online public engagement platforms.</p> <p>Results</p> <p>The benefits of public engagement include creating an informed citizenry, generating new ideas from the public, increasing the chances of research being adopted, increasing public trust, and answering ethical research questions. Public engagement also fosters global communication, enables shared experiences and methodology, standardizes strategy, and generates global viewpoints. This is especially pertinent to the developing world, as it encourages previously marginalized populations to participate on a global stage. One of the core issues at stake in public engagement is global governance of science and technology. Also, beyond benefiting society at large, public engagement in science offers benefits to the scientific enterprise itself.</p> <p>Conclusion</p> <p>Successful public engagement with developing world stakeholders will be a critical part of implementing new services and technologies. Interactive engagement platforms, such as the Internet, have the potential to unite people globally around relevant health issues.</p
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