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In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.
A new target design is presented to model high-energy radiative accretion shocks in polars. In this paper, we present the experimental results obtained on the GEKKO XII laser facility for the POLAR project. The experimental results are compared with 2D FCI2 simulations to characterize the dynamics and the structure of plasma flow before and after the collision. The good agreement between simulations and experimental data confirms the formation of a reverse shock where cooling losses start modifying the post-shock region. With the multi-material structure of the target, a hydrodynamic collimation is exhibited and a radiative structure coupled with the reverse shock is highlighted in both experimental data and simulations. The flexibility of the laser energy produced on GEKKO XII allowed us to produce high-velocity flows and study new and interesting radiation hydrodynamic regimes between those obtained on the LULI2000 and Orion laser facilities.
OBJECTIVES/SPECIFIC AIMS: Discrimination within the healthcare system and physician distrust have been associated with adverse clinical outcomes for people living with HIV; however, many studies do not link these variables to biological data. We hypothesize that perceived healthcare discrimination and physician distrust associates with higher longitudinal viremia among HIV-positive women. METHODS/STUDY POPULATION: A 2006 cross-sectional survey assessed healthcare-based discrimination and physician trust in 92 HIV-positive and 46 high-risk HIV-negative women from the Washington DC Women’s Interagency HIV Study (DC-WIHS). In addition, we identified HIV viral load trajectories and demographics from the HIV-positive women who contributed≥4 semi-annual visits from 1994 to 2015. Viral suppression was defined by assay detection limits (<80 to <20 copies/mL). Group-based probability trajectory analyses grouped women based on longitudinal viral load patterns, and identified 3 groups: sustained viremia (n=32) with low-viral suppression over time, intermittent viremia (n=27) with varying suppression over time, and non-viremia (n=33) with high-longitudinal viral suppression. Ordinal logistic regression models assessed trajectory group and discrimination variables, controlling for demographics, using stepwise selection with significance level of α=0.05. RESULTS/ANTICIPATED RESULTS: Most women were African American (60%), insured at the time of visit (89%) and nonsmokers (56%). While physician trust did not differ by HIV viral trajectory group, trust was lower among HIV-negative women compared with HIV-positive women (p=0.03). Over 1 in 5 HIV-positive women reported discrimination in the healthcare system based on HIV status (21.3%). Report of discrimination based on drug/alcohol use was higher among HIV-negative participants (19.2% vs. 6.5%, p=0.01). Among women with longitudinal sustained viremia, report of discrimination based on race ethnicity (29%, p=0.004) and sexual orientation (15.6%, p=0.008) were higher than within the nonviremic and intermittent trajectory groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Physician trust did not associate with increased longitudinal viral suppression among HIV-positive women in Washington, DC. Lack of physician trust among high-risk HIV-negative women could have implications for uptake of prevention methods. Reports of discrimination vary between HIV-positive and HIV-negative women in the Washington, DC area. The findings of healthcare system distrust among HIV-negative women has implications outside the realm of HIV, as this lack of trust may impact risk for other disease states among similar populations of women.
We present a multi-frequency study of the intermediate spiral SAB(r)bc type galaxy NGC 6744, using available data from the Chandra X-Ray telescope, radio continuum data from the Australia Telescope Compact Array and Murchison Widefield Array, and Wide-field Infrared Survey Explorer infrared observations. We identify 117 X-ray sources and 280 radio sources. Of these, we find nine sources in common between the X-ray and radio catalogues, one of which is a faint central black hole with a bolometric radio luminosity similar to the Milky Way’s central black hole. We classify 5 objects as supernova remnant (SNR) candidates, 2 objects as likely SNRs, 17 as H ii regions, 1 source as an AGN; the remaining 255 radio sources are categorised as background objects and one X-ray source is classified as a foreground star. We find the star-formation rate (SFR) of NGC 6744 to be in the range 2.8–4.7 M⊙~yr − 1 signifying the galaxy is still actively forming stars. The specific SFR of NGC 6744 is greater than that of late-type spirals such as the Milky Way, but considerably less that that of a typical starburst galaxy.
Little is known about the association of cortical Aβ with depression and anxiety among cognitively normal (CN) elderly persons.
We conducted a cross-sectional study derived from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota; involving CN persons aged ≥ 60 years that underwent PiB-PET scans and completed Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Cognitive diagnosis was made by an expert consensus panel. Participants were classified as having abnormal (≥1.4; PiB+) or normal PiB-PET (<1.4; PiB−) using a global cortical to cerebellar ratio. Multi-variable logistic regression analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for age and sex.
Of 1,038 CN participants (53.1% males), 379 were PiB+. Each one point symptom increase in the BDI (OR = 1.03; 1.00–1.06) and BAI (OR = 1.04; 1.01–1.08) was associated with increased odds of PiB-PET+. The number of participants with BDI > 13 (clinical depression) was greater in the PiB-PET+ than PiB-PET- group but the difference was not significant (OR = 1.42; 0.83–2.43). Similarly, the number of participants with BAI > 10 (clinical anxiety) was greater in the PiB-PET+ than PiB-PET− group but the difference was not significant (OR = 1.77; 0.97–3.22).
As expected, depression and anxiety levels were low in this community-dwelling sample, which likely reduced our statistical power. However, we observed an informative albeit weak association between increased BDI and BAI scores and elevated cortical amyloid deposition. This observation needs to be tested in a longitudinal cohort study.
Previous research suggests that the experience of abuse and neglect in childhood has negative implications for physical health in adulthood. Using data from the Minnesota Longitudinal Study of Risk and Adaptation (N = 115), the present research examined the predictive significance of childhood physical abuse, sexual abuse, and physical/cognitive neglect for multilevel assessments of physical health at midlife (age 37–39 years), including biomarkers of cardiometabolic risk, self-reports of quality of health, and a number of health problems. Analyses revealed that childhood physical/cognitive neglect, but not physical or sexual abuse, predicted all three health outcomes in middle adulthood, even when controlling for demographic risk factors and adult health maintenance behaviors. We discuss possible explanations for the unique significance of neglect in this study and suggest future research that could clarify previous findings regarding the differential impact of different types of abuse and neglect on adult health.
In the popularly accepted empirical model for pulsar emission, bunches of charged particles traveling along open field lines near the magnetic pole emit curvature radiation. Such radiation is linearly polarized. Most of the radiation is assumed to be emitted from a ring shaped region centered on the pole (the hollow cone model). We have calculated the expected average polarization using this model and find them to be in disagreement with observations. The addition of a second ring inside the first with orthogonal polarization solves this problem. This new model explains other observed features of pulsar emission including discontinuities in position-angle profiles and multicomponent profiles. Plasma interactions might account for a second ring.
Ischaemic heart disease and stroke are vascular events with serious health consequences worldwide. Recent genetic and epigenetic techniques have revealed many genetic determinants of these vascular events and simplified the approaches to research focused on ischaemic heart disease and stroke. The pathogenetic mechanisms of ischaemic heart disease and stroke are complex, with mitochondrial involvement (partially or entirely) recently gaining substantial support. Not only can mitochondrial reactive oxygen species give rise to ischaemic heart disease and stroke by production of oxidised low-density lipoprotein and induction of apoptosis, but the impact on pericytes contributes directly to the pathogenesis. Over the past two decades, publications implicate the causative role of nuclear genes in the development of ischaemic heart disease and stroke, in contrast to the potential role of mitochondrial DNA (mtDNA) in the pathophysiology of the disorders, which is much less understood, although recent studies do demonstrate that the involvement of mitochondria and mtDNA in the development of ischaemic heart disease and stroke is likely to be larger than originally thought, with the novel discovery of links among mitochondria, mtDNA and vascular events. Here we explore the molecular events and mtDNA alterations in relation to the role of mitochondria in ischaemic heart disease and stroke.
A few studies have evaluated the impact of clinical trial results on practice in paediatric cardiology. The Infant Single Ventricle (ISV) Trial results published in 2010 did not support routine use of the angiotensin-converting enzyme inhibitor enalapril in infants with single-ventricle physiology. We sought to assess the influence of these findings on clinical practice.
A web-based survey was distributed via e-mail to over 2000 paediatric cardiologists, intensivists, cardiothoracic surgeons, and cardiac advance practice nurses during three distribution periods. The results were analysed using McNemar’s test for paired data and Fisher’s exact test.
The response rate was 31.5% (69% cardiologists and 65% with >10 years of experience). Among respondents familiar with trial results, 74% reported current practice consistent with trial findings versus 48% before trial publication (p<0.001); 19% used angiotensin-converting enzyme inhibitor in this population “almost always” versus 36% in the past (p<0.001), and 72% reported a change in management or improved confidence in treatment decisions involving this therapy based on the trial results. Respondents familiar with trial results (78%) were marginally more likely to practise consistent with the trial results than those unfamiliar (74 versus 67%, p=0.16). Among all respondents, 28% reported less frequent use of angiotensin-converting enzyme inhibitor over the last 3 years.
Within 5 years of publication, the majority of respondents was familiar with the Infant Single Ventricle Trial results and reported less frequent use of angiotensin-converting enzyme inhibitor in single-ventricle infants; however, 28% reported not adjusting their clinical decisions based on the trial’s findings.
Glaciers on southwestern Bylot Island in the Canadian Arctic flow from an alpine setting in high-grade crystalline Archean terrane, on to coastal lowlands underlain by clastic sedimentary strata of Cretaceous to Tertiary age. We have used the contrasting mineralogy of the substrate as a tool to study subglacial entrainment and transport of debris in two large piedmont glaciers on Bylot Island. High chlorite/ and mica-illite/smectite ratios indicate that most basal debris is derived from crystalline rocks underlying the upper reaches of the glaciers. The subglacial accretion of Cretaceous–Tertiary sediments appears restricted to the lowermost part of the basal zone and is most noticeable near the glaciers’ termini. Ice associated with discrete silly–sandy debris layers is characterized by an isotopic signature indicative of refreezing of meltwater at the glacier sole. The compositional, textural and isotopic characteristics of basal sediment and ice lead us to conclude that subglacial entrainment through basal ice accretion occurs in both the upper and marginal parts of the glaciers.
Training for the clinical research workforce does not sufficiently prepare workers for today’s scientific complexity; deficiencies may be ameliorated with training. The Enhancing Clinical Research Professionals’ Training and Qualifications developed competency standards for principal investigators and clinical research coordinators.
Clinical and Translational Science Awards representatives refined competency statements. Working groups developed assessments, identified training, and highlighted gaps.
Forty-eight competency statements in 8 domains were developed.
Training is primarily investigator focused with few programs for clinical research coordinators. Lack of training is felt in new technologies and data management. There are no standardized assessments of competence.
The translation of discoveries to drugs, devices, and behavioral interventions requires well-prepared study teams. Execution of clinical trials remains suboptimal due to varied quality in design, execution, analysis, and reporting. A critical impediment is inconsistent, or even absent, competency-based training for clinical trial personnel.
In 2014, the National Center for Advancing Translational Science (NCATS) funded the project, Enhancing Clinical Research Professionals’ Training and Qualifications (ECRPTQ), aimed at addressing this deficit. The goal was to ensure all personnel are competent to execute clinical trials. A phased structure was utilized.
This paper focuses on training recommendations in Good Clinical Practice (GCP). Leveraging input from all Clinical and Translational Science Award hubs, the following was recommended to NCATS: all investigators and study coordinators executing a clinical trial should understand GCP principles and undergo training every 3 years, with the training method meeting the minimum criteria identified by the International Conference on Harmonisation GCP.
We anticipate that industry sponsors will acknowledge such training, eliminating redundant training requests. We proposed metrics to be tracked that required further study. A separate task force was composed to define recommendations for metrics to be reported to NCATS.
We experimentally study resonant interactions of oblique surface gravity waves in a large basin. Our results strongly extend previous experimental results performed mainly for perpendicular or collinear wave trains. We generate two oblique waves crossing at an acute angle, while we control their frequency ratio, steepnesses and directions. These mother waves mutually interact and give birth to a resonant wave whose properties (growth rate, resonant response curve and phase locking) are fully characterized. All our experimental results are found in good quantitative agreement with four-wave interaction theory with no fitting parameter. Off-resonance experiments are also reported and the relevant theoretical analysis is conducted and validated.
The European Union Network ANTENA started to work in October 1993. During these last three years, several collaborative projects have been undertaken. ANTENA has offered a very good opportunity for most of the European people doing asteroseismology to work together. The asteroseismological networks STEPHI and STACC have run within the framework of the project, obtaining fairly good results. New instrumentation has also been developed, such as the Four-Channel Stellar Photometer.
Patients with psychosis display the so-called ‘Jumping to Conclusions’ bias (JTC) – a tendency for hasty decision-making in probabilistic reasoning tasks. So far, only a few studies have evaluated the JTC bias in ‘at-risk mental state’ (ARMS) patients, specifically in ARMS samples fulfilling ‘ultra-high risk’ (UHR) criteria, thus not allowing for comparisons between different ARMS subgroups.
In the framework of the PREVENT (secondary prevention of schizophrenia) study, a JTC task was applied to 188 patients either fulfilling UHR criteria or presenting with cognitive basic symptoms (BS). Similar data were available for 30 healthy control participants matched for age, gender, education and premorbid verbal intelligence. ARMS patients were identified by the Structured Interview for Prodromal Symptoms (SIPS) and the Schizophrenia Proneness Instrument – Adult Version (SPI-A).
The mean number of draws to decision (DTD) significantly differed between ARM -subgroups: UHR patients made significantly less draws to make a decision than ARMS patients with only cognitive BS. Furthermore, UHR patients tended to fulfil behavioural criteria for JTC more often than BS patients. In a secondary analysis, ARMS patients were much hastier in their decision-making than controls. In patients, DTD was moderately associated with positive and negative symptoms as well as disorganization and excitement.
Our data indicate an enhanced JTC bias in the UHR group compared to ARMS patients with only cognitive BS. This underscores the importance of reasoning deficits within cognitive theories of the developing psychosis. Interactions with the liability to psychotic transitions and therapeutic interventions should be unravelled in longitudinal studies.
Development of polymers with antimicrobial characteristics can avoid deterioration and assist in containing spread of pathogens harmful to human health. This study aimed to compare the antimicrobial and mechanical properties of polymeric matrices containing organic antimicrobial additives. Silver organomodified bentonite (Ag_bentonite) and organochlorine molecule in a masterbatch based polyethylene (Cl_PE) were tested in proportion of 2% in a thermoplastic elastomeric formulation. The polymeric matrices were prepared by melt mixing and evaluated in tensile and antimicrobial properties against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) strains. The additives were characterized by thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The nanoscale of Ag_bentonite was verified by SEM. TGA assay showed that Cl_PE is more sensitive to heat than Ag_bentonite. As a result of this lower thermal stability, the addition of Cl_PE reduced the tensile properties of the compound. The sample with Cl_PE was effective against both bacterial strains, reducing the populations of S. aureus and E. coli in 99 and 96%, respectively. The addition of Ag_bentonite did not affect the tensile strength and decreased in 97 and 40% S. aureus and E. coli populations, respectively. The results indicate that the use of organic additives is promissory, but further modifications in processing must be necessary.
The δ Scuti stars are pulsating variables located in the lower part of the Cepheid instability strip with spectral types from A2 to F0 on the main sequence, and from A3 to F5 at luminosity class III. These variables show short periods (< 0.3day) and luminosity amplitudes ranging from a few thousandths of a magnitude to several tenths. Over the last few years, significant progress has been made in the detection of pulsating modes in the framework of the multisite campaigns, e.g. STACC (Frandsen et al. 1996), DSN (Breger et al. 1998), STEPHI (Michel et al. 2000). For the 1998 STEPHI IX photometry campaign, the δ Scuti star V534 Tau of the Pleiades cluster (see Table 1) was monitored during a three week, three continent run. Preliminary results are reported here.
Some results of the photometry multi-site observations of two δ Scuti stars, V624 Tau and HD 23194, are presented. The observations were carried out in the framework of a STEPHI network in 1999. We collected 343 hours of useful data and detected seven frequencies in V624 Tau and two frequencies in HD 23194.
We have observed Procyon with the fiber-fed échelle spectrograph ELODIE coupled with a Fabry-Perot etalon at the 193-cm of the Observatoire de Haute Provence (France) over 5 nights during 1997 December – 1998 January. Here, we present the results of a search for solar-like oscillations on this star and the performance of this instrumentation for asteroseismology. The power spectra show an excess of signal between 0.42 mHz and 1.46 mHz, which could be due to stellar oscillations.