333 research outputs found
Pneumatic tools for vitreoretinal surgery
One of the difficulties of microsurgery is learning how to control physiological tremors. The pneumatic tool eliminates the physiological tremor, but no tactile feedback is provided. The manual tremor when closing the forceps is completely eliminated and the exact target can be more easily grabbed. Forceps closure pressure can rise up to 50 psi, whereas the scissors can be used in two modes: multicut and proportional. When performing bimanual surgery the pedal range is divided into two steps: in the first step, the forceps are controlled, and in the second step, the forceps remain closed. At the same time the scissors start to work in the preselected mode. No adverse events occurred and no iatrogenic retinal breaks were produced. Precision and control sensation were a grateful surprise
The Effects of Thermonuclear Reaction Rate Variations on Nova Nucleosynthesis: A Sensitivity Study
We investigate the effects of thermonuclear reaction rate uncertainties on
nova nucleosynthesis. One-zone nucleosynthesis calculations have been performed
by adopting temperature-density-time profiles of the hottest hydrogen-burning
zone (i.e., the region in which most of the nucleosynthesis takes place). We
obtain our profiles from 7 different, recently published, hydrodynamic nova
simulations covering peak temperatures in the range from Tpeak=0.145-0.418 GK.
For each of these profiles, we individually varied the rates of 175 reactions
within their associated errors and analyzed the resulting abundance changes of
142 isotopes in the mass range below A=40. In total, we performed 7350 nuclear
reaction network calculations. We use the most recent thermonuclear reaction
rate evaluations for the mass ranges A=1-20 and A=20-40. For the theoretical
astrophysicist, our results indicate the extent to which nova nucleosynthesis
calculations depend on presently uncertain nuclear physics input, while for the
experimental nuclear physicist our results represent at least a qualitative
guide for future measurements at stable and radioactive ion beam facilities. We
find that present reaction rate estimates are reliable for predictions of Li,
Be, C and N abundances in nova nucleosynthesis. However, rate uncertainties of
several reactions have to be reduced significantly in order to predict more
reliable O, F, Ne, Na, Mg, Al, Si, S, Cl and Ar abundances. Results are
presented in tabular form for each adopted nova simulation.Comment: Accepted for publication in The Astrophysical Journal Suppl. Serie
Managing Achilles Pain (the MAP study) – A process evaluation of data collection methods
Background Process evaluations explore the way in which a study was conducted. The Managing Achilles Pain study (MAP study) had the primary aim of assessing the feasibility of the protocol for a future large longitudinal cohort study that would investigate the association and predictive relationship of self-efficacy, working alliance and expectations with outcome in the management of Achilles tendinopathy. Objectives This study aimed to evaluate the processes conducted in the MAP study by exploring the acceptability of the study procedures from the participants' and physiotherapists' perspectives. Design A qualitative evaluation using semi-structured telephone interviews. Method All physiotherapists and participants who participated in the MAP study were invited. Data from physiotherapists (n = 6) and participants (n = 7) were transcribed and analysed using the Framework Approach. Findings From the physiotherapists' perspective 4 themes were identified relating to obstacles; (1) access to participants; (2) recall; (3) visibility; (4) time, and 4 themes were identified relating to facilitating success; (1) training; (2) motivation; (3) incentives; (4) simplicity. From the participants' perspective 2 themes were identified relating to obstacles; (1) information from the physiotherapist; (2) follow up, 3 themes were identified relating to facilitating success; (1) motivation; (2) website; (3) questionnaire, and 1 theme relating to unintended consequences of participating in the study; positive experience. Conclusions Although clinicians are enthused to be involved in research, organisational factors impact levels of engagement. Key influences to optimising the potential success of a study include the publicising of the study; optimising verbal recruitment strategies; and clarity in communication
Fumarate-loaded electrospun nanofibers with anti-inflammatory activity for fast recovery of mild skin burns
In the biomedical sector the availability of engineered scaffolds and dressings that control and reduce inflammatory states is highly desired, particularly for the management of burn wounds. In this work, we demonstrate for the first time, to the best of our knowledge, that electrospun fibrous dressings of poly(octyl cyanoacrylate) (POCA) combined with polypropylene fumarate (PPF) possess anti-inflammatory activity and promote the fast and effective healing of mild skin burns in an animal model. The fibers produced had an average diameter of (0.8 ± 0.1) µm and they were able to provide a conformal coverage of the injured tissue. The application of the fibrous mats on the burned tissue effectively reduced around 80% of the levels of pro-inflammatory cytokines in the first 48 h in comparison with un-treated animals, and enhanced skin epithelialization. From histological analysis, the skin thickness of the animals treated with POCA : PPF dressings appeared similar to that of one of the naïve animals: (13.7 ± 1.4) µm and (14.3 ± 2.5) µm for naïve and treated animals, respectively. The density of dermal cells was comparable as well: (1100 ± 112) cells mm−2 and (1358 ± 255) cells mm−2 for naïve and treated mice, respectively. The results demonstrate the suitability of the electrospun dressings in accelerating and effectively promoting the burn healing process
Resonant heating and substrate-mediated cooling of a single C60 molecule in a tunnel junction
We study the influence of different metallic substrates on the electron
induced heating and heat dissipation of single C60 molecules in the junction of
a low temperature scanning tunneling microscope. The electron current passing
through the molecule produces a large amount of heat due to electron-phonon
coupling, eventually leading to thermal decomposition of the fullerene cage.
The power for decomposition varies with electron energy and reflects the
resonance structure participating in the transport. The average value for
thermal decomposition of C60 on Cu(110) amounts to 21 W, while it is much
lower on Pb(111) (2.9 W) and on Au(111) (1.0 W). We ascribe this
difference to the amount of charge transfer into C60 upon adsorption on the
different surfaces, which facilitates molecular vibron quenching by
electron-hole pair creation
Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort
Background
β-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (Type I) reactions mediated by antigen-specific IgE.
Objective
To identify genetic predisposing factors for immediate reactions to β-lactam antibiotics.
Methods
Patients with a clinical history of immediate hypersensitivity reactions to either penicillins or cephalosporins, which were immunologically confirmed, were recruited from allergy clinics. A genome-wide association study (GWAS) was conducted on 662 patients (the discovery cohort) with a diagnosis of immediate hypersensitivity and the main finding was replicated in a cohort of 98 Spanish cases, recruited using the same diagnostic criteria as the discovery cohort.
Results
GWAS identified rs71542416 within the Class II HLA region as the top hit (P = 2x10-14); this was in linkage disequilibrium with HLA-DRB1*10:01 (OR = 2.93 P = 5.4x10-7) and HLA-DQA1*01:05 (OR=2.93, P=5.4x10-7). Haplotype analysis identified that HLA-DRB1*10:01 was a risk factor even without the HLA-DQA1*01:05 allele. The association with HLA-DRB1*10:01 was replicated in another cohort, with the meta-analysis of the discovery and replication cohorts showing that HLA-DRB1*10:01 increased the risk of immediate hypersensitivity at a genome-wide level (OR = 2.96 P=4.1x10-9). No association with HLA-DRB1*10:01 was identified in 268 patients with delayed hypersensitivity reactions to β-lactams.
Conclusion
HLA-DRB1*10:01 predisposed to immediate hypersensitivity reactions to penicillins. Further work to identify other predisposing HLA and non-HLA loci is required.
Clinical implications
This novel insight into the mechanisms of immediate reactions associated with penicillins may be of use in risk stratifying patients where penicillin cannot be excluded as an etiological agent
Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.
OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age
A-002 (Varespladib), a phospholipase A2 inhibitor, reduces atherosclerosis in guinea pigs
<p>Abstract</p> <p>Background</p> <p>The association of elevated serum levels of secretory phospholipase A<sub>2 </sub>(sPLA<sub>2</sub>) in patients with cardiovascular disease and their presence in atherosclerotic lesions suggest the participation of sPLA<sub>2 </sub>enzymes in this disease. The presence of more advanced atherosclerotic lesions in mice that overexpress sPLA<sub>2 </sub>enzymes suggest their involvement in the atherosclerotic process. Therefore, the sPLA<sub>2 </sub>family of enzymes could provide reasonable targets for the prevention and treatment of atherosclerosis. Thus, A-002 (varespladib), an inhibitor of sPLA<sub>2</sub>enzymes, is proposed to modulate the development of atherosclerosis.</p> <p>Methods</p> <p>Twenty-four guinea pigs were fed a high saturated fat, high cholesterol diet (0.25%) for twelve weeks. Animals were treated daily with A-002 (n = 12) or vehicle (10% aqueous acacia; n = 12) by oral gavage. After twelve weeks, animals were sacrificed and plasma, heart and aorta were collected. Plasma lipids were measured by enzymatic methods, lipoprotein particles size by nuclear magnetic resonance, aortic cytokines by a colorimetric method, and aortic sinus by histological analyses.</p> <p>Results</p> <p>Plasma total cholesterol, HDL cholesterol and triglycerides were not different among groups. However, the levels of inflammatory cytokines interleukin (IL)-10, IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly reduced in the treatment group. This group also had a significant 27% reduction in cholesterol accumulation in aorta compared with placebo group. Morphological analysis of aortic sinus revealed that the group treated with A-002 reduced atherosclerotic lesions by 24%.</p> <p>Conclusion</p> <p>The use of A-002 may have a beneficial effect in preventing diet-induced atherosclerosis in guinea pigs.</p
Pogostick: A New Versatile piggyBac Vector for Inducible Gene Over-Expression and Down-Regulation in Emerging Model Systems
Non-traditional model systems need new tools that will enable them to enter the field of functional genetics. These tools should enable the exploration of gene function, via knock-downs of endogenous genes, as well as over-expression and ectopic expression of transgenes.We constructed a new vector called Pogostick that can be used to over-express or down-regulate genes in organisms amenable to germ line transformation by the piggyBac transposable element. Pogostick can be found at www.addgene.org, a non-profit plasmid repository. The vector currently uses the heat-shock promoter Hsp70 from Drosophila to drive transgene expression and, as such, will have immediate applicability to organisms that can correctly interpret this promotor sequence. We detail how to clone candidate genes into this vector and test its functionality in Drosophila by targeting a gene coding for the fluorescent protein DsRed. By cloning a single DsRed copy into the vector, and generating transgenic lines, we show that DsRed mRNA and protein levels are elevated following heat-shock. When cloning a second copy of DsRed in reverse orientation into a flanking site, and transforming flies constitutively expressing DsRed in the eyes, we show that endogenous mRNA and protein levels drop following heat-shock. We then test the over-expression vector, containing the complete cDNA of Ultrabithorax (Ubx) gene, in an emerging model system, Bicyclus anynana. We produce a transgenic line and show that levels of Ubx mRNA expression rise significantly following a heat-shock. Finally, we show how to obtain genomic sequence adjacent to the Pogostick insertion site and to estimate transgene copy number in genomes of transformed individuals.This new vector will allow emerging model systems to enter the field of functional genetics with few hurdles
Variation in dopamine D2 and serotonin 5-HT2A receptor genes is associated with working memory processing and response to treatment with antipsychotics
Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with
antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these
phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal
working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T
allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics
compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect
on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with secondgeneration
antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the
rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the
attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during
working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment
in two independent samples of patients with schizophrenia (n¼63 and n¼54, respectively), consistent with the previously reported
separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological
prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that
further exploration is needed to better understand the clinical consequences of these genotype–phenotype relationships
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