2,713 research outputs found
Comparing within-person effects from multivariate longitudinal models.
Several multivariate models are motivated to answer similar developmental questions regarding within-person (intraindividual) effects between two or more constructs over time, yet the within-person effects tested by each model are distinct. In this paper, we clarify the types of within-person inferences that can be made from each model. Whereas previous research has focused on detecting whether within-person effects exist over development, the present work can be used to understand the nature of these relationships. We compare each modeling approach using an example investigating the concurrent development of mother-child closeness and mother-child conflict. Our findings demonstrate that fundamentally different conclusions about developmental processes may be reached depending on which model is used, and we demonstrate a framework for making sense of seemingly contradictory findings
Effects of Cultured Adrenal Chromaffin Cell Implants on Hindlimb Reflexes of the 6-OHDA Lesioned Rat
The effects of implantation of cultured
adrenal medullary cells on the recovery of
neurotransmitter specific reflex activity were
studied in the rat spinal cord using electrophysiological
testing methods. Cell suspensions
of cultured neonatal adrenal medullary
chromaffin (AM) cells (which produce
catecholamines), or Schwann (Sc) cells (controls)
were implanted into the lumbar region of the
spinal cord 2 weeks after catecholamine (CA)
denervation by intracisternal injection of 6-hydroxydopamine
(6-OHDA). All cells were
taken from 7 day neonates and cultured for 10
days in the presence of nerve growth factor
(NGF). Three months after implantation, the
extent of implant-associated recovery of reflex
activity was determined by measuring electromyogram
(EMG) activity and force associated
with the long latency component of the hindlimb
withdrawal reflex (which is CA modulated).
After the electrophysiological testing, rats were
anesthetized, and the spinal cords were rapidly
removed and frozen. Spinal cords were sectioned
longitudinally, and implanted cells were
visualized using glyoxylic acid techniques.
Labelled sections were examined to determine
cell survival. Results indicate that 1) chromaffin
cells survive for 3 months in the segments of the
cord into which they have been implanted and
2) rats implanted with AM cells have
significantly more forceful withdrawal reflexes
than those that received Sc cells or received no
implant after lesioning
Potential use for chronic pain: Poly(Ethylene Glycol)-Poly(Lactic-Co-Glycolic Acid) nanoparticles enhance the effects of Cannabis-Based terpenes on calcium influx in TRPV1-Expressing cells
The objective of these in vitro studies was to investigate the impact of the encapsulation of three cannabis-based terpenes, namely β-myrcene (MC), β-caryophyllene (CPh), and nerolidol (NL), on their potential efficacy in pain management. Terpene-encapsulated poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (PEG-PLGA NPs) were prepared by an emulsion-solvent evaporation method. The terpene-loaded NPs were examined in HEK293 cells that express the nociceptive transient receptor potential vanilloid- 1 (TRPV1), an ion channel involved in pain perception. TRPV1 activation was assessed by monitoring calcium influx kinetics over 1 h in cells pre-treated with the fluorescent indicator Fluo-4. In addition, the fluorescence intensity changes induced by the NPs in living cells were also explored by a fluorescence microscope. Furthermore, the cytotoxicity of the terpene-loaded NPs was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenyl tetrazolium bromide (MTT) proliferation assay. The terpene-loaded NPs had a diameter in the range of 250–350 nm and a zeta potential of approximately −20 mV. The encapsulation efficiency was 18.5%, 51.3%, and 60.3% for MC, NL, and CPh NPs, respectively. The nano-formulations significantly increased the fluorescence intensity in comparison with free terpenes. Furthermore, combinations of terpene-loaded NPs produced significantly higher calcium responses when compared to combinations of free terpenes. Similar findings were shown by the fluorescence images. In conclusion, the terpene-PLGA NPs can be promising therapeutics for more effective pain management
Cellular Responses and Tissue Depots for Nanoformulated Antiretroviral Therapy.
Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, CD3, CD11b, F4/80, and GR-1 antibodies. The localization of nanoATV within leukocyte cell subsets was determined by confocal microscopy. Combined FACS and ultra-performance liquid chromatography tandem mass-spectrometry assays determined nanoATV carriages by cell-based vehicles. A robust granulocyte, but not peritoneal macrophage nanoATV response paralleled zymosan A treatment. ATV levels were highest at sites of injection in peritoneal or muscle macrophages, dependent on the injection site. The spleen and liver served as nanoATV tissue depots while drug levels in lymph nodes were higher than those recorded in plasma. Dual polymer and cell labeling demonstrated a nearly exclusive drug reservoir in macrophages within the liver and spleen. Overall, nanoART induces innate immune responses coincident with rapid tissue macrophage distribution. Taken together, these works provide avenues for therapeutic development designed towards chemical eradication of human immunodeficiency viral infection
Cellular Responses and Tissue Depots for Nanoformulated Antiretroviral Therapy.
Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, CD3, CD11b, F4/80, and GR-1 antibodies. The localization of nanoATV within leukocyte cell subsets was determined by confocal microscopy. Combined FACS and ultra-performance liquid chromatography tandem mass-spectrometry assays determined nanoATV carriages by cell-based vehicles. A robust granulocyte, but not peritoneal macrophage nanoATV response paralleled zymosan A treatment. ATV levels were highest at sites of injection in peritoneal or muscle macrophages, dependent on the injection site. The spleen and liver served as nanoATV tissue depots while drug levels in lymph nodes were higher than those recorded in plasma. Dual polymer and cell labeling demonstrated a nearly exclusive drug reservoir in macrophages within the liver and spleen. Overall, nanoART induces innate immune responses coincident with rapid tissue macrophage distribution. Taken together, these works provide avenues for therapeutic development designed towards chemical eradication of human immunodeficiency viral infection
Comparing alternating pressure mattresses and high-specification foam mattresses to prevent pressure ulcers in high-risk patients: the PRESSURE 2 RCT
Background:
Pressure ulcers (PUs) are a burden to patients, carers and health-care providers. Specialist mattresses minimise the intensity and duration of pressure on vulnerable skin sites in at-risk patients.
Primary objective:
Time to developing a new PU of category ≥ 2 in patients using an alternating pressure mattress (APM) compared with a high-specification foam mattress (HSFM).
Design:
A multicentre, Phase III, open, prospective, planned as an adaptive double-triangular group sequential, parallel-group, randomised controlled trial with an a priori sample size of 2954 participants. Randomisation used minimisation (incorporating a random element).
Setting:
The trial was set in 42 secondary and community inpatient facilities in the UK.
Participants:
Adult inpatients with evidence of acute illness and at a high risk of PU development.
Interventions and follow-up:
APM or HSFM – the treatment phase lasted a maximum of 60 days; the final 30 days were post-treatment follow-up.
Main outcome measures:
Time to event.
Results:
From August 2013 to November 2016, 2029 participants were randomised to receive either APM (n = 1016) or HSFM (n = 1013). Primary end point – 30-day final follow-up: of the 2029 participants in the intention-to-treat population, 160 (7.9%) developed a new PU of category ≥ 2. There was insufficient evidence of a difference between groups for time to new PU of category ≥ 2 [Fine and Gray model HR 0.76, 95% confidence interval (CI) 0.56 to 1.04; exact p-value of 0.0890 and 2% absolute difference]. Treatment phase sensitivity analysis: 132 (6.5%) participants developed a new PU of category ≥ 2 between randomisation and end of treatment phase. There was a statistically significant difference in the treatment phase time-to-event sensitivity analysis (Fine and Gray model HR 0.66, 95% CI 0.46 to 0.93; p = 0.0176 and 2.6% absolute difference). Secondary end points – 30-day final follow-up: new PUs of category ≥ 1 developed in 350 (17.2%) participants, with no evidence of a difference between mattress groups in time to PU development, (Fine and Gray model HR 0.83, 95% CI 0.67 to 1.02; p-value = 0.0733 and absolute difference 3.1%). New PUs of category ≥ 3 developed in 32 (1.6%) participants with insufficient evidence of a difference between mattress groups in time to PU development (Fine and Gray model HR 0.81, 95% CI 0.40 to 1.62; p = 0.5530 and absolute difference 0.4%). Of the 145 pre-existing PUs of category 2, 89 (61.4%) healed – there was insufficient evidence of a difference in time to healing (Fine and Gray model HR 1.12, 95% CI 0.74 to 1.68; p = 0.6122 and absolute difference 2.9%). Health economics – the within-trial and long-term analysis showed APM to be cost-effective compared with HSFM; however, the difference in costs models are small and the quality-adjusted life-year gains are very small. There were no safety concerns. Blinded photography substudy – the reliability of central blinded review compared with clinical assessment for PUs of category ≥ 2 was ‘very good’ (kappa statistic 0.82, prevalence- and bias-adjusted kappa 0.82). Quality-of-life substudy – the Pressure Ulcer Quality of Life – Prevention (PU-QoL-P) instrument meets the established criteria for reliability, construct validity and responsiveness.
Limitations:
A lower than anticipated event rate.
Conclusions:
In acutely ill inpatients who are bedfast/chairfast and/or have a category 1 PU and/or localised skin pain, APMs confer a small treatment phase benefit that is diminished over time. Overall, the APM patient compliance, very low PU incidence rate observed and small differences between mattresses indicate the need for improved indicators for targeting of APMs and individualised decision-making. Decisions should take into account skin status, patient preferences (movement ability and rehabilitation needs) and the presence of factors that may be potentially modifiable through APM allocation, including being completely immobile, having nutritional deficits, lacking capacity and/or having altered skin/category 1 PU.
Future work:
Explore the relationship between mental capacity, levels of independent movement, repositioning and PU development. Explore ‘what works for whom and in what circumstances’.
Trial registration:
Current Controlled Trials ISRCTN01151335.
Funding:
This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 52. See the NIHR Journals Library website for further project information
Noticias de BahÃa Academia
El Vivero de la ECCD. Las Amenazadas Tortugas de Cerro Paloma, Isabel. El Daño de los Chivos al Volcán Alcedo. Las Colecciones del Museo de la ECCD. Chivos en Pinta, Otra Vez? Existe un Guadalupe River en Galápagos? Avistamiento de un Tirano del Este. Tomar Palabras del Pasado. ¡Es Scalesia Atractyloides! El Beagle, Bote de Investigación de la ECCD. Alcedo al DÃa. Exposición de Arte a Beneficio de Alcedo. Nueva Construcción. Actividad Geológica? Ciencia de Alta TecnologÃa. Mas Noticias Sobre Pinta. Primer Registro de la Garza Verde (Butorides Viriscens) en las Islas Galápagos. Un Vuelo sobre los Volcanes del Norte de Isabela
Stellar Spin-Orbit Misalignment in a Multiplanet System
Stars hosting hot Jupiters are often observed to have high obliquities,
whereas stars with multiple co-planar planets have been seen to have low
obliquities. This has been interpreted as evidence that hot-Jupiter formation
is linked to dynamical disruption, as opposed to planet migration through a
protoplanetary disk. We used asteroseismology to measure a large obliquity for
Kepler-56, a red giant star hosting two transiting co-planar planets. These
observations show that spin-orbit misalignments are not confined to hot-Jupiter
systems. Misalignments in a broader class of systems had been predicted as a
consequence of torques from wide-orbiting companions, and indeed
radial-velocity measurements revealed a third companion in a wide orbit in the
Kepler-56 system.Comment: Accepted for publication in Science, published online on October 17
2013; PDF includes main article and supplementary materials (65 pages, 27
figures, 7 tables); v2: small correction to author lis
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