We have developed a significantly improved composite material for applications to chemiresistors, which are resistance-based sensors for volatile organic compounds. This material is a polymer ...composite containing Au-coated magnetic particles organized into electrically conducting pathways by magnetic fields. This improved material overcomes the various problems inherent to conventional carbon-black chemiresistors, while achieving an unprecedented magnitude of response. When exposed to chemical vapors, the polymer swells only slightly, yet this is amplified into large, reversible resistance changes—as much as 9 decades at a swelling of only 1.5%. These conductor-insulator transitions occur over such a narrow range of analyte vapor concentration that these devices can be described as chemical switches. We demonstrate that the sensitivity and response range of these sensors can be tailored over a wide range by controlling the stress within the composite, including through the application of a magnetic field. Such tailorable sensors can be used to create sensor arrays that can accurately determine analyte concentration over a broad concentration range, or can be used to create logic circuits that signal a particular chemical environment. It is shown through combined mass-sorption and conductance measurements, that the response curve of any individual sensor is a function of polymer swelling alone. This has the important implication that individual sensor calibration requires testing with only a single analyte. In addition, we demonstrate a method for analyte discrimination based on sensor response kinetics, which is independent of analyte concentration. This method allows for discrimination even between chemically similar analytes. Lastly, additional variables associated with the composite and their effects on sensor response are explored.
We introduce the AGORA project, a comprehensive numerical study of well-resolved galaxies within the LCDM cosmology. Cosmological hydrodynamic simulations with force resolutions of ~100 proper pc or ...better will be run with a variety of code platforms to follow the hierarchical growth, star formation history, morphological transformation, and the cycle of baryons in and out of 8 galaxies with halo masses M_vir ~= 1e10, 1e11, 1e12, and 1e13 Msun at z=0 and two different ("violent" and "quiescent") assembly histories. The numerical techniques and implementations used in this project include the smoothed particle hydrodynamics codes GADGET and GASOLINE, and the adaptive mesh refinement codes ART, ENZO, and RAMSES. The codes will share common initial conditions and common astrophysics packages including UV background, metal-dependent radiative cooling, metal and energy yields of supernovae, and stellar initial mass function. These are described in detail in the present paper. Subgrid star formation and feedback prescriptions will be tuned to provide a realistic interstellar and circumgalactic medium using a non-cosmological disk galaxy simulation. Cosmological runs will be systematically compared with each other using a common analysis toolkit, and validated against observations to verify that the solutions are robust - i.e., that the astrophysical assumptions are responsible for any success, rather than artifacts of particular implementations. The goals of the AGORA project are, broadly speaking, to raise the realism and predictive power of galaxy simulations and the understanding of the feedback processes that regulate galaxy "metabolism." The proof-of-concept dark matter-only test of the formation of a galactic halo with a z=0 mass of M_vir ~= 1.7e11 Msun by 9 different versions of the participating codes is also presented to validate the infrastructure of the project.
1. Marine mammals may be negatively affected by anthropogenic noise. Behavioural response studies (BRS) aim to establish a relationship between noise exposure conditions (dose) from a potential ...Stressor and associated behavioural responses of animals. A recent series of BRS have focused on the effects of naval sonar sounds on cetaceans. Here, we review the current state of understanding of naval sonar impact on marine mammals and highlight knowledge gaps and future research priorities. 2. Many marine mammal species exhibit responses to naval sonar sounds. However, responses vary between and within individuals and populations, highlighting the importance of exposure context in modulating dose-response relationships. 3. There is increasing support from both terrestrial and marine systems for the risk-disturbance hypothesis as an explanation for underlying response processes. This proposes that sonar sounds may be perceived by animals as a threat, evoking a response shaped by the underlying species-specific risk of predation and antipredator strategy. An understanding of responses within both the dose-response and risk-disturbance frameworks may enhance our ability to predict responsiveness for unstudied species and populations. 4. Many observed behavioural responses are energetically costly, but the way that these responses may lead to long-term individual and population-level impacts is poorly understood. 5. Synthesis and applications. Behavioural response studies have greatly improved our understanding of the potential effects of naval sonar on marine mammals. Despite data gaps, we believe a dose-response approach within a risk-disturbance framework will enhance our ability to predict responsiveness for unstudied species and populations. W e advocate for (1) regulatory frameworks to utilize peer-reviewed research findings when making predictions of impact, (2) regulatory frameworks to account for the inherent uncertainty in predictions of impact and (3) investment in monitoring programmes that are both directed by recent research and offer opportunities for validation of predictions at the individual and population level.
Scatter-hoarding birds find their caches using spatial memory and have an enlarged hippocampus. Finding a cache site could be achieved using either Recollection (a discrete recalling of previously ...experienced information) or Familiarity (a feeling of “having encountered something before”). In humans, these two processes can be distinguished using receiver operating characteristic (ROC) curves. ROC curves for olfactory memory in rats have shown the hippocampus is involved in Recollection, but not Familiarity. We test the hypothesis that food-hoarding birds, having a larger hippocampus, primarily use Recollection to find their caches. We validate a novel method of constructing ROC curves in humans and apply this method to cache retrieval by coal tits (
Periparus ater
). Both humans and birds mainly use Familiarity in finding their caches, with lower contribution of Recollection. This contribution is not significantly different from chance in birds, but a small contribution cannot be ruled out. Memory performance decreases with increasing retention interval in birds. The ecology of food-hoarding Parids makes it plausible that they mainly use Familiarity in the memory for caches. The larger hippocampus could be related to associating cache contents and temporal context with cache locations, rather than Recollection of the spatial information itself.
Predators adapt their foraging behavior to exploit a variety of prey in a range of environments. Short-finned pilot whales are wide-ranging predators in tropical and sub-tropical oceans, but most ...previous studies of their foraging ecology have been conducted near oceanic islands. We deployed sound- and movement-recording tags on 43 short-finned pilot whales off Cape Hatteras, North Carolina, USA, to measure their foraging behavior in a continental shelf-break ecosystem and investigate how variation in the environment shapes their behavior. Overall, the foraging behavior of pilot whales off Cape Hatteras was similar to that of their counterparts from island-associated habitats. Off Cape Hatteras, pilot whales made foraging dives as deep as 1077 m (mean: 445 m), lasting up to 23 min (mean: 12.8 min), with sprints (pursuit at speeds over 3 m s
-1
and up to 6.9 m s
-1
) in more than half of foraging dives. However, tagged whales off Cape Hatteras produced higher buzz rates (11.3 buzzes dive
-1
), foraged more extensively in daytime hours, and engaged in more frequent benthic foraging than island-associated ecotypes. By parsing the echoic scene generated by the animal’s own echolocation clicks, we show that pilot whales off Cape Hatteras frequently exploit bathymetric features for foraging, with benthic dives resulting in higher prey capture attempts than pelagic dives. The ability of these predators to strategically adapt foraging strategies to local habitat features likely contributes to their ecological success and may allow them to adjust to shifts in prey distributions in a rapidly changing Anthropocene ocean.
To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression.
Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We ...harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression.
Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer.
Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study.
Overall mortality and CM.
Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio SMR = 0.95, 95% confidence interval CI, 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR = 1.04, 95% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio aHR = 0.88, 0.89, 0.90, 1.11) and CM (aHR = 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration.
Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
To begin a process of standardizing the methods for reporting clinical data in the field of uveitis.
Consensus workshop.
Members of an international working group were surveyed about diagnostic ...terminology, inflammation grading schema, and outcome measures, and the results used to develop a series of proposals to better standardize the use of these entities. Small groups employed nominal group techniques to achieve consensus on several of these issues.
The group affirmed that an anatomic classification of uveitis should be used as a framework for subsequent work on diagnostic criteria for specific uveitic syndromes and that the classification of uveitis entities should be on the basis of the location of the inflammation and not on the presence of structural complications. Issues regarding the use of the terms “intermediate uveitis,” “pars planitis,” “panuveitis,” and descriptors of the onset and course of the uveitis were addressed. The following were adopted: standardized grading schema for anterior chamber cells, anterior chamber flare, and for vitreous haze; standardized methods of recording structural complications of uveitis; standardized definitions of outcomes, including “inactive” inflammation, “improvement” and “worsening” of the inflammation, and “corticosteroid sparing,” and standardized guidelines for reporting visual acuity outcomes.
A process of standardizing the approach to reporting clinical data in uveitis research has begun, and several terms have been standardized.
BACKGROUND:Nevirapine (NVP)-based combination antiretroviral therapy is routinely prescribed to infants deemed at high risk of vertical HIV infection in our centers. We evaluated NVP pharmacokinetics ...and safety of this regimen.
METHODS:Neonates were recruited prospectively between September 2012 and April 2015 or enrolled retrospectively if treated similarly before prospective study initiation. NVP was dosed at 150 mg/m daily for 14 days, then twice daily for 14 days. NVP levels were drawn at weeks 1, 2, and 4 target trough (NVP-T)3–8 mg/L.
RESULTS:Thirty-three neonates were included (23 prospectively). Median gestational age (GA) and birth weight were 38 weeks (32–41 weeks) and 2.9 kg (1.5–4.2 kg), respectively. Median NVP-Ts were 8.2 mg/L (1.6–25.1 mg/L), 3.5 mg/L (1.6–6.8 mg/L), and 4.3 mg/L (0.1–19.9 mg/L) at weeks 1, 2, and 4, respectively. The proportions with therapeutic NVP-T were 42%, 61%, and 73% at these same timepoints. Median apparent oral clearance (CL/F) increased from 0.05 L·kg·h (0.01–0.50 L·kg·h) at week 2 to 0.18 L·kg·h (0.01–0.78 L·kg·h) at week 4. Increased drug exposure area under the curve (AUCτ) correlated with younger GA (r = 0.459, P = 0.032) and lower birth weight (r = 0.542, P = 0.009). The most common adverse events potentially attributable to combination antiretroviral therapy were transient asymptomatic hyperlactatemia (26%), anemia (24.7%), and neutropenia (22.1%).
CONCLUSIONS:Treatment dose NVP was generally well-tolerated and associated with normalization of trough levels over time in most cases without dose adjustment. Lower empiric dosing is recommended for infants <34 weeks of GA. Routine therapeutic drug monitoring may not be required for infants ≥34 weeks of GA.
The NIH-led research response to COVID-19 Collins, Francis; Adam, Stacey; Colvis, Christine ...
Science (American Association for the Advancement of Science),
02/2023, Letnik:
379, Številka:
6631
Journal Article
Recenzirano
Investment, collaboration, and coordination have been key.