5,758 research outputs found
Albumin activates the AKT signalling pathway and protects B-chronics lymphocytic leukemia cells from chlorambucil- and radiation-induced apoptosis
Understanding disease control: influence of epidemiological and economic factors
We present a local spread model of disease transmission on a regular network
and compare different control options ranging from treating the whole
population to local control in a well-defined neighborhood of an infectious
individual. Comparison is based on a total cost of epidemic, including cost of
palliative treatment of ill individuals and preventive cost aimed at
vaccination or culling of susceptible individuals. Disease is characterized by
pre- symptomatic phase which makes detection and control difficult. Three
general strategies emerge, global preventive treatment, local treatment within
a neighborhood of certain size and only palliative treatment with no
prevention. The choice between the strategies depends on relative costs of
palliative and preventive treatment. The details of the local strategy and in
particular the size of the optimal treatment neighborhood weakly depends on
disease infectivity but strongly depends on other epidemiological factors. The
required extend of prevention is proportional to the size of the infection
neighborhood, but this relationship depends on time till detection and time
till treatment in a non-nonlinear (power) law. In addition, we show that the
optimal size of control neighborhood is highly sensitive to the relative cost,
particularly for inefficient detection and control application. These results
have important consequences for design of prevention strategies aiming at
emerging diseases for which parameters are not known in advance
Postcopulatory Sexual Selection Is Associated with Reduced Variation in Sperm Morphology
The evolutionary role of postcopulatory sexual selection in shaping male reproductive traits, including sperm morphology, is well documented in several taxa. However, previous studies have focused almost exclusively on the influence of sperm competition on variation among species. In this study we tested the hypothesis that intraspecific variation in sperm morphology is driven by the level of postcopulatory sexual selection in passerine birds.Using two proxy measures of sperm competition level, (i) relative testes size and (ii) extrapair paternity level, we found strong evidence that intermale variation in sperm morphology is negatively associated with the degree of postcopulatory sexual selection, independently of phylogeny.Our results show that the role of postcopulatory sexual selection in the evolution of sperm morphology extends to an intraspecific level, reducing the variation towards what might be a species-specific 'optimum' sperm phenotype. This finding suggests that while postcopulatory selection is generally directional (e.g., favouring longer sperm) across avian species, it also acts as a stabilising evolutionary force within species under intense selection, resulting in reduced variation in sperm morphology traits. We discuss some potential evolutionary mechanisms for this pattern
Psychosocial adversity and socioeconomic position during childhood and epigenetic age: analysis of two prospective cohort studies
Psychosocial adversity in childhood (e.g. abuse) and low socioeconomic position (SEP) can have significant lasting effects on social and health outcomes. DNA methylation-based biomarkers are highly correlated with chronological age; departures of methylation-predicted age from chronological age can be used to define a measure of age acceleration, which may represent a potential biological mechanism linking environmental exposures to later health outcomes. Using data from two cohorts of women Avon Longitudinal Study of Parents and Children, (ALSPAC), N = 989 and MRC National Survey of Health and Development, NSHD, N = 773), we assessed associations of SEP, psychosocial adversity in childhood (parental physical or mental illness or death, parental separation, parental absence, sub-optimal maternal bonding, sexual, emotional and physical abuse and neglect) and a cumulative score of these psychosocial adversity measures, with DNA methylation age acceleration in adulthood (measured in peripheral blood at mean chronological ages 29 and 47 in ALSPAC and buccal cells at age 53 in NSHD). Sexual abuse was strongly associated with age acceleration in ALSPAC (sexual abuse data were not available in NSHD), e.g. at the 47-year time point sexual abuse associated with a 3.41 years higher DNA methylation age (95% CI 1.53 to 5.29) after adjusting for childhood and adulthood SEP. No associations were observed between low SEP, any other psychosocial adversity measure or the cumulative psychosocial adversity score and age acceleration. DNA methylation age acceleration is associated with sexual abuse, suggesting a potential mechanism linking sexual abuse with adverse outcomes. Replication studies with larger sample sizes are warranted
Desynchronizing effect of high-frequency stimulation in a generic cortical network model
Transcranial Electrical Stimulation (TCES) and Deep Brain Stimulation (DBS)
are two different applications of electrical current to the brain used in
different areas of medicine. Both have a similar frequency dependence of their
efficiency, with the most pronounced effects around 100Hz. We apply
superthreshold electrical stimulation, specifically depolarizing DC current,
interrupted at different frequencies, to a simple model of a population of
cortical neurons which uses phenomenological descriptions of neurons by
Izhikevich and synaptic connections on a similar level of sophistication. With
this model, we are able to reproduce the optimal desynchronization around
100Hz, as well as to predict the full frequency dependence of the efficiency of
desynchronization, and thereby to give a possible explanation for the action
mechanism of TCES.Comment: 9 pages, figs included. Accepted for publication in Cognitive
Neurodynamic
Geometric Mixing, Peristalsis, and the Geometric Phase of the Stomach
Mixing fluid in a container at low Reynolds number - in an inertialess
environment - is not a trivial task. Reciprocating motions merely lead to
cycles of mixing and unmixing, so continuous rotation, as used in many
technological applications, would appear to be necessary. However, there is
another solution: movement of the walls in a cyclical fashion to introduce a
geometric phase. We show using journal-bearing flow as a model that such
geometric mixing is a general tool for using deformable boundaries that return
to the same position to mix fluid at low Reynolds number. We then simulate a
biological example: we show that mixing in the stomach functions because of the
"belly phase": peristaltic movement of the walls in a cyclical fashion
introduces a geometric phase that avoids unmixing.Comment: Revised, published versio
Sperm design and variation in the New World blackbirds (Icteridae)
Post-copulatory sexual selection (PCSS) is thought to be one of the evolutionary forces responsible for the rapid and divergent evolution of sperm design. However, whereas in some taxa particular sperm traits are positively associated with PCSS, in other taxa, these relationships are negative, and the causes of these different patterns across taxa are poorly understood. In a comparative study using New World blackbirds (Icteridae), we tested whether sperm design was influenced by the level of PCSS and found significant positive associations with the level of PCSS for all sperm components but head length. Additionally, whereas the absolute length of sperm components increased, their variation declined with the intensity of PCSS, indicating stabilizing selection around an optimal sperm design. Given the diversity of, and strong selection on, sperm design, it seems likely that sperm phenotype may influence sperm velocity within species. However, in contrast to other recent studies of passerine birds, but consistent with several other studies, we found no significant link between sperm design and velocity, using four different species that vary both in sperm design and PCSS. Potential reasons for this discrepancy between studies are discussed
The Pioneer Anomaly
Radio-metric Doppler tracking data received from the Pioneer 10 and 11
spacecraft from heliocentric distances of 20-70 AU has consistently indicated
the presence of a small, anomalous, blue-shifted frequency drift uniformly
changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was
interpreted as a constant sunward deceleration of each particular spacecraft at
the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of
the Newton's gravitational inverse-square law has become known as the Pioneer
anomaly; the nature of this anomaly remains unexplained. In this review, we
summarize the current knowledge of the physical properties of the anomaly and
the conditions that led to its detection and characterization. We review
various mechanisms proposed to explain the anomaly and discuss the current
state of efforts to determine its nature. A comprehensive new investigation of
the anomalous behavior of the two Pioneers has begun recently. The new efforts
rely on the much-extended set of radio-metric Doppler data for both spacecraft
in conjunction with the newly available complete record of their telemetry
files and a large archive of original project documentation. As the new study
is yet to report its findings, this review provides the necessary background
for the new results to appear in the near future. In particular, we provide a
significant amount of information on the design, operations and behavior of the
two Pioneers during their entire missions, including descriptions of various
data formats and techniques used for their navigation and radio-science data
analysis. As most of this information was recovered relatively recently, it was
not used in the previous studies of the Pioneer anomaly, but it is critical for
the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living
Reviews in Relativit
A systematic review of strategies to recruit and retain primary care doctors
Background There is a workforce crisis in primary care. Previous research has looked at the reasons underlying recruitment and retention problems, but little research has looked at what works to improve recruitment and retention. The aim of this systematic review is to evaluate interventions and strategies used to recruit and retain primary care doctors internationally. Methods A systematic review was undertaken. MEDLINE, EMBASE, CENTRAL and grey literature were searched from inception to January 2015.Articles assessing interventions aimed at recruiting or retaining doctors in high income countries, applicable to primary care doctors were included. No restrictions on language or year of publication. The first author screened all titles and abstracts and a second author screened 20%. Data extraction was carried out by one author and checked by a second. Meta-analysis was not possible due to heterogeneity. Results 51 studies assessing 42 interventions were retrieved. Interventions were categorised into thirteen groups: financial incentives (n=11), recruiting rural students (n=6), international recruitment (n=4), rural or primary care focused undergraduate placements (n=3), rural or underserved postgraduate training (n=3), well-being or peer support initiatives (n=3), marketing (n=2), mixed interventions (n=5), support for professional development or research (n=5), retainer schemes (n=4), re-entry schemes (n=1), specialised recruiters or case managers (n=2) and delayed partnerships (n=2). Studies were of low methodological quality with no RCTs and only 15 studies with a comparison group. Weak evidence supported the use of postgraduate placements in underserved areas, undergraduate rural placements and recruiting students to medical school from rural areas. There was mixed evidence about financial incentives. A marketing campaign was associated with lower recruitment. Conclusions This is the first systematic review of interventions to improve recruitment and retention of primary care doctors. Although the evidence base for recruiting and care doctors is weak and more high quality research is needed, this review found evidence to support undergraduate and postgraduate placements in underserved areas, and selective recruitment of medical students. Other initiatives covered may have potential to improve recruitment and retention of primary care practitioners, but their effectiveness has not been established
Proposals for evaluating the regularity of a scientist'sresearch output
Evaluating the career of individual scientists according to their scientific output is a common bibliometric problem. Two aspects are classically taken into account: overall productivity and overall diffusion/impact, which can be measured by a plethora of indicators that consider publications and/or citations separately or synthesise these two quantities into a single number (e.g. h-index). A secondary aspect, which is sometimes mentioned in the rules of competitive examinations for research position/promotion, is time regularity of one researcher's scientific output. Despite the fact that it is sometimes invoked, a clear definition of regularity is still lacking. We define it as the ability of generating an active and stable research output over time, in terms of both publications/ quantity and citations/diffusion. The goal of this paper is introducing three analysis tools to perform qualitative/quantitative evaluations on the regularity of one scientist's output in a simple and organic way. These tools are respectively (1) the PY/CY diagram, (2) the publication/citation Ferrers diagram and (3) a simplified procedure for comparing the research output of several scientists according to their publication and citation temporal distributions (Borda's ranking). Description of these tools is supported by several examples
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