265 research outputs found
Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity
Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria
The role of lumbar puncture in children with suspected central nervous system infection
BACKGROUND: The use of the lumbar puncture in the diagnosis of central nervous system infection in acutely ill children is controversial. Recommendations have been published but it is unclear whether they are being followed. METHODS: The medical case notes of 415 acute medical admissions in a children's hospital were examined to identify children with suspected central nervous system infection and suspected meningococcal septicaemia. We determined whether lumbar punctures were indicated or contraindicated, whether they had been performed, and whether the results contributed to the patients' management. RESULTS: Fifty-two children with suspected central nervous system infections, and 43 with suspected meningococcal septicaemia were identified. No lumbar punctures were performed in patients with contraindications, but only 25 (53%) of 47 children with suspected central nervous system infection and no contraindications received a lumbar puncture. Lumbar puncture findings contributed to the management in 18 (72%) of these patients, by identifying a causative organism or excluding bacterial meningitis. CONCLUSION: The recommendations for undertaking lumbar punctures in children with suspected central nervous system infection are not being followed because many children that should receive lumbar punctures are not getting them. When they are performed, lumbar puncture findings make a useful contribution to the patients' management
CONFIRM: a double-blind, placebo controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial
Background: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure
to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched,
with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted
treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need
to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited.
Methods: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in
the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336
patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be
recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to
epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min
intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab
increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free
survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed
according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and
for other time-to-event endpoints).
Discussion: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab
in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely
to become the new standard of care in the UK
The climate sensitivity of Norway spruce [Picea abies (L.) Karst.] in the southeastern European Alps
Tree ring chronologies were developed from trees growing at two sites in Slovenia which differed in their ecological and climatological characteristics. Ring width, maximum latewood density, annual height increment and latewood cellulose carbon isotope composition were developed at both sites and time-series verified against instrumental climate data over the period (AD 1960–AD 2002). Ring width sensitivity to summer temperature is site-dependent, with contrasting responses at alpine and lowland sites. Maximum density responds to September temperatures, suggesting lignification after cell division has ended for the season. Stable carbon isotopes have great potential, responding to summer temperature at oth alpine and lowland stands. Height increment appears relatively insensitive to climate, and is likely to be dominated by local stand dynamics
Zigzag Turning Preference of Freely Crawling Cells
The coordinated motion of a cell is fundamental to many important biological
processes such as development, wound healing, and phagocytosis. For eukaryotic
cells, such as amoebae or animal cells, the cell motility is based on crawling
and involves a complex set of internal biochemical events. A recent study
reported very interesting crawling behavior of single cell amoeba: in the
absence of an external cue, free amoebae move randomly with a noisy, yet,
discernible sequence of ‘run-and-turns’ analogous to the
‘run-and-tumbles’ of swimming bacteria. Interestingly, amoeboid
trajectories favor zigzag turns. In other words, the cells bias their crawling
by making a turn in the opposite direction to a previous turn. This property
enhances the long range directional persistence of the moving trajectories. This
study proposes that such a zigzag crawling behavior can be a general property of
any crawling cells by demonstrating that 1) microglia, which are the immune
cells of the brain, and 2) a simple rule-based model cell, which incorporates
the actual biochemistry and mechanics behind cell crawling, both exhibit similar
type of crawling behavior. Almost all legged animals walk by alternating their
feet. Similarly, all crawling cells appear to move forward by alternating the
direction of their movement, even though the regularity and degree of zigzag
preference vary from one type to the other
Phenomenological analysis of ATP dependence of motor protein
In this study, through phenomenological comparison of the velocity-force data
of processive motor proteins, including conventional kinesin, cytoplasmic
dynein and myosin V, we found that, the ratio between motor velocities of two
different ATP concentrations is almost invariant for any substall, superstall
or negative external loads. Therefore, the velocity of motor can be well
approximated by a Michaelis-Menten like formula V=\atp k(F)L/(\atp +K_M),
with the step size, and the external load dependent rate of one
mechanochemical cycle of motor motion in saturated ATP solution. The difference
of Michaelis-Menten constant for substall, superstall and negative
external load indicates, the ATP molecule affinity of motor head for these
three cases are different, though the expression of as a function of
might be unchanged for any external load . Verifications of this
Michaelis-Menten like formula has also been done by fitting to the recent
experimental data
Associations between an Obesity Related Genetic Variant (FTO rs9939609) and Prostate Cancer Risk
Observational studies suggest that obese men have a lower risk of incident prostate cancer, but an increased risk of advanced and fatal cancers. These observations could be due to confounding, detection bias, or a biological effect of obesity. Genetic studies are less susceptible to confounding than observational epidemiology and can suggest how associations between phenotypes (such as obesity) and diseases arise. To determine whether the associations between obesity and prostate cancer are causal, we conducted a genetic association study of the relationship between a single nucleotide polymorphism known to be associated with obesity (FTO rs9939609) and prostate cancer. Data are from a population-based sample of 1550 screen-detected prostate cancers, 1815 age- and general practice matched controls with unrestricted prostate specific antigen (PSA) values and 1175 low-PSA controls (PSA <0.5 ng/ml). The rs9939609 A allele, which was associated with higher BMI in the sample, was inversely associated with overall (odds ratio (OR) versus all controls = 0.93; 95% confidence interval (CI): 0.85–1.02 p = 0.12 per allele) and low-grade (OR = 0.90; 0.81–0.99 p = 0.03 per allele) prostate cancer risk, but positively associated with high-grade cancer among cases (OR high- versus low-grade cancer = 1.16; 0.99–1.37 p = 0.07 per allele). Although evidence for these effects was weak, they are consistent with observational data based on BMI phenotypes and suggest that the observed association between obesity and prostate cancer is not due to confounding. Further research should confirm these findings, extend them to other BMI-related genetic variants and determine whether they are due to detection bias or obesity-related hormonal changes
A Dimer of the Toll-Like Receptor 4 Cytoplasmic Domain Provides a Specific Scaffold for the Recruitment of Signalling Adaptor Proteins
The Toll-like receptor 4 (TLR4) is a class I transmembrane receptor expressed on the surface of immune system cells. TLR4 is activated by exposure to lipopolysaccharides derived from the outer membrane of Gram negative bacteria and forms part of the innate immune response in mammals. Like other class 1 receptors, TLR4 is activated by ligand induced dimerization, and recent studies suggest that this causes concerted conformational changes in the receptor leading to self association of the cytoplasmic Toll/Interleukin 1 receptor (TIR) signalling domain. This homodimerization event is proposed to provide a new scaffold that is able to bind downstream signalling adaptor proteins. TLR4 uses two different sets of adaptors; TRAM and TRIF, and Mal and MyD88. These adaptor pairs couple two distinct signalling pathways leading to the activation of interferon response factor 3 (IRF-3) and nuclear factor κB (NFκB) respectively. In this paper we have generated a structural model of the TLR4 TIR dimer and used molecular docking to probe for potential sites of interaction between the receptor homodimer and the adaptor molecules. Remarkably, both the Mal and TRAM adaptors are strongly predicted to bind at two symmetry-related sites at the homodimer interface. This model of TLR4 activation is supported by extensive functional studies involving site directed mutagenesis, inhibition by cell permeable peptides and stable protein phosphorylation of receptor and adaptor TIR domains. Our results also suggest a molecular mechanism for two recent findings, the caspase 1 dependence of Mal signalling and the protective effects conferred by the Mal polymorphism Ser180Leu
Implementing a guideline for the treatment of type 2 diabetics: results of a Cluster- Randomized Controlled Trial (C-RCT)
<p>Abstract</p> <p>Background</p> <p>In Italy many diabetics still lack adequate care in general practice. We assessed the effectiveness of different strategies for the implementation of an evidence-based guideline for the management of non-complicated type 2 diabetes among General Practitioners (GPs) of Lazio region.</p> <p>Methods</p> <p>Three-arm cluster-randomised controlled trial with GPs as units of randomisation (clusters). 252 GPs were randomised either to an active strategy (training module with administration of the guideline), or to a passive dissemination (administration of the guideline only), or to usual care (control). Data on prescriptions of tests and drugs were collected by existing information systems, whereas patients' data came from GPs' databases. Process outcomes were measured at the cluster level one year after the intervention. Primary outcomes concerned the measurement of glycosilated haemoglobin and the commissioning of micro- and macrovascular complications assessment tests. In order to assess the physicians' drug prescribing behaviour secondary outcomes were also calculated.</p> <p>Results</p> <p>GPs identified 6395 uncomplicated type 2 patients with a high prevalence of cardiovascular risk factors. Data on GPs baseline performance show low proportions of glycosilated haemoglobin assessments. Results of the C-RCT analysis indicate that the active implementation strategy was ineffective relating to all primary outcomes (respectively, OR 1.06 [95% IC: 0.76–1.46]; OR 1.07 [95% IC: 0.80–1.43]; OR 1.4 [95% IC:0.91–2.16]. Similarly, passive dissemination of the guideline showed no effect.</p> <p>Conclusion</p> <p>In our region compliance of GPs with guidelines was not enhanced by a structured learning programme. Implementation through organizational measures appears to be essential to induce behavioural changes.</p> <p>Trial registration</p> <p>ISRCTN80116232</p
Stratification of the severity of critically ill patients with classification trees
<p>Abstract</p> <p>Background</p> <p>Development of three classification trees (CT) based on the CART (<it>Classification and Regression Trees</it>), CHAID (<it>Chi-Square Automatic Interaction Detection</it>) and C4.5 methodologies for the calculation of probability of hospital mortality; the comparison of the results with the APACHE II, SAPS II and MPM II-24 scores, and with a model based on multiple logistic regression (LR).</p> <p>Methods</p> <p>Retrospective study of 2864 patients. Random partition (70:30) into a Development Set (DS) n = 1808 and Validation Set (VS) n = 808. Their properties of discrimination are compared with the ROC curve (AUC CI 95%), Percent of correct classification (PCC CI 95%); and the calibration with the Calibration Curve and the Standardized Mortality Ratio (SMR CI 95%).</p> <p>Results</p> <p>CTs are produced with a different selection of variables and decision rules: CART (5 variables and 8 decision rules), CHAID (7 variables and 15 rules) and C4.5 (6 variables and 10 rules). The common variables were: inotropic therapy, Glasgow, age, (A-a)O2 gradient and antecedent of chronic illness. In VS: all the models achieved acceptable discrimination with AUC above 0.7. CT: CART (0.75(0.71-0.81)), CHAID (0.76(0.72-0.79)) and C4.5 (0.76(0.73-0.80)). PCC: CART (72(69-75)), CHAID (72(69-75)) and C4.5 (76(73-79)). Calibration (SMR) better in the CT: CART (1.04(0.95-1.31)), CHAID (1.06(0.97-1.15) and C4.5 (1.08(0.98-1.16)).</p> <p>Conclusion</p> <p>With different methodologies of CTs, trees are generated with different selection of variables and decision rules. The CTs are easy to interpret, and they stratify the risk of hospital mortality. The CTs should be taken into account for the classification of the prognosis of critically ill patients.</p
- …