2,585 research outputs found
A dual function for Pex3p in peroxisome formation and inheritance
Saccharomyces cerevisiae Pex3p has been shown to act at the ER during de novo peroxisome formation. However, its steady state is at the peroxisomal membrane, where its role is debated. Here we show that Pex3p has a dual function: one in peroxisome formation and one in peroxisome segregation. We show that the peroxisome retention factor Inp1p interacts physically with Pex3p in vitro and in vivo, and split-GFP analysis shows that the site of interaction is the peroxisomal membrane. Furthermore, we have generated PEX3 alleles that support peroxisome formation but fail to support recruitment of Inp1p to peroxisomes, and as a consequence are affected in peroxisome segregation. We conclude that Pex3p functions as an anchor for Inp1p at the peroxisomal membrane, and that this function is independent of its role at the ER in peroxisome biogenesis
An observational study of patient characteristics associated with the mode of admission to acute stroke services in North East, England
Objective
Effective provision of urgent stroke care relies upon admission to hospital by emergency ambulance and may involve pre-hospital redirection. The proportion and characteristics of patients who do not arrive by emergency ambulance and their impact on service efficiency is unclear. To assist in the planning of regional stroke services we examined the volume, characteristics and prognosis of patients according to the mode of presentation to local services.
Study design and setting
A prospective regional database of consecutive acute stroke admissions was conducted in North East, England between 01/09/10-30/09/11. Case ascertainment and transport mode were checked against hospital coding and ambulance dispatch databases.
Results
Twelve acute stroke units contributed data for a mean of 10.7 months. 2792/3131 (89%) patients received a diagnosis of stroke within 24 hours of admission: 2002 arrivals by emergency ambulance; 538 by private transport or non-emergency ambulance; 252 unknown mode. Emergency ambulance patients were older (76 vs 69 years), more likely to be from institutional care (10% vs 1%) and experiencing total anterior circulation symptoms (27% vs 6%). Thrombolysis treatment was commoner following emergency admission (11% vs 4%). However patients attending without emergency ambulance had lower inpatient mortality (2% vs 18%), a lower rate of institutionalisation (1% vs 6%) and less need for daily carers (7% vs 16%). 149/155 (96%) of highly dependent patients were admitted by emergency ambulance, but none received thrombolysis.
Conclusion
Presentations of new stroke without emergency ambulance involvement were not unusual but were associated with a better outcome due to younger age, milder neurological impairment and lower levels of pre-stroke dependency. Most patients with a high level of pre-stroke dependency arrived by emergency ambulance but did not receive thrombolysis. It is important to be aware of easily identifiable demographic groups that differ in their potential to gain from different service configurations
Isolation and identification of cobalt- and caesium-resistant bacteria from a nuclear fuel storage pond
One of the issues facing the nuclear power industry is how to store spent nuclear fuel which is contaminated with radionuclides produced during nuclear fission, including caesium ((134)Cs(+), (135)Cs(+) and (137)Cs(+)) and cobalt ((60)Co(2+)). In this study, we have isolated Co(2+)- and Cs(+)-resistant bacteria from water collected from a nuclear fuel storage pond. The most resistant Cs(+) and Co(2+) isolates grew in the presence of 500 mM CsCl and 3 mM CoCl2. Strain Cs67-2 is resistant to fourfold more Cs(+) than Cupriavidus metallidurans str. CH34 making it the most Cs(+)-resistant strain identified to date. The Cs(+)-resistant isolates were closely related to bacteria in the Serratia and Yersinia genera, while the Co(2+)-resistant isolates were closely related to the Curvibacter and Tardiphaga genera. These new isolates could be used for bioremediation
Don't Stop Thinking About Leptoquarks: Constructing New Models
We discuss the general framework for the construction of new models
containing a single, fermion number zero scalar leptoquark of mass GeV which can both satisfy the D0/CDF search constraints as well as
low energy data, and can lead to both neutral and charged current-like final
states at HERA. The class of models of this kind necessarily contain new
vector-like fermions with masses at the TeV scale which mix with those of the
Standard Model after symmetry breaking. In this paper we classify all models of
this type and examine their phenomenological implications as well as their
potential embedding into SUSY and non-SUSY GUT scenarios. The general coupling
parameter space allowed by low energy as well as collider data for these models
is described and requires no fine-tuning of the parameters.Comment: Modified text, added table, and updated reference
Sensitivity and Specificity of Multiple Kato-Katz Thick Smears and a Circulating Cathodic Antigen Test for Schistosoma mansoni Diagnosis Pre- and Post-repeated-Praziquantel Treatment
Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This âgold standardâ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings
The ethics of âTrials within Cohortsâ (TwiCs): 2nd international symposium - London, UK. 7-8 November 2016
On 7-8
th
November 2016, 60 people with an interest in the
â
Trials
within Cohorts
â
(TwiCs) approach for randomised controlled trial design
met in London. The purpose of this 2
nd
TwiCs international symposium
was to share perspectives and experiences on ethical aspects of the
TwiCs design, discuss how TwiCs relate to the current ethical frame-
work, provide a forum in which to discuss and debate ethical issues
and identify future directions for conceptual and empirical research.
The symposium was supported by the Wellcome Trust and the NIHR
CLAHRC Yorkshire and Humber and organised by members of the
TwiCs network led by Clare Relton and attended by people from the
UK, the Netherlands, Norway, Canada and USA. The two-day sympo-
sium enabled an international group to meet and share experiences
of the TwiCs design (also known as the
â
cohort multiple RCT design
â
),
and to discuss plans for future research. Over the two days, invited
plenary talks were interspersed by discussions, posters and mini pre-
sentations from bioethicists, triallists and health research regulators.
Key findings of the symposium were: (1) It is possible to make a
compelling case to ethics committees that TwiCs designs are ap-
propriate and ethical; (2) The importance of wider considerations
around the ethics of inefficient trial designs; and (3) some questions
about the ethical requirements for content and timing of informed
consent for a study using the TwiCs design need to be decided on
a case-by-case basis
Recommended from our members
Multi-omic association study identifies DNA methylation-mediated genotype and smoking exposure effects on lung function in children living in urban settings
Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV1) (p = 2.4x10-9; ÎČz = -0.31, 95% CI = -0.41- -0.21). Mendelian randomization and mediation analyses revealed that this genetic effect on FEV1 was partially mediated by DNA methylation levels at this locus in airway epithelial cells, which were also associated with environmental tobacco smoke exposure (p = 0.015). Promoter-enhancer interactions in airway epithelial cells revealed chromatin interaction loops between FEV1-associated variants in TDRD9 and the promoter region of the PPP1R13B gene, a stimulator of p53-mediated apoptosis. Expression of PPP1R13B in airway epithelial cells was significantly associated the FEV1 risk alleles (p = 1.3x10-5; ÎČ = 0.12, 95% CI = 0.06â0.17). These combined results highlight a potential novel mechanism for reduced lung function in urban youth resulting from both genetics and smoking exposure
Characteristics and outcome of infants with candiduria in neonatal intensive care - a Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study
<p>Abstract</p> <p>Background</p> <p>There is limited information in the literature on the presentation and prognosis of candidal urinary tract infection (UTI) in infants in the neonatal intensive care unit (NICU).</p> <p>Methods</p> <p>This was a prospective cohort study performed in 13 Canadian NICUs. Infants with candidal UTI without extra-renal candidal infection at presentation were enrolled.</p> <p>Results</p> <p>Thirty infants fit the study criteria. Median birth weight and gestational age were 2595 grams (range 575-4255) and 35 weeks (range 24-41) with 10 infants being < 30 weeks gestation. The most common primary underlying diagnosis was congenital heart disease (n = 10). The median age at initial diagnosis was 16 days (range 6-84 days). Renal ultrasonography findings were compatible with possible fungal disease in 15 of the 26 infants (58%) in whom it was performed. Treatment was variable, but fluconazole and either amphotericin B deoxycholate or lipid-based amphotericin B in combination or sequentially were used most frequently. Extra-renal candidiasis subsequently developed in 4 infants. In 2 of these 4 infants, dissemination happened during prolonged courses of anti-fungal therapy. Three of 9 deaths were considered to be related to candidal infection. No recurrences of candiduria or episodes of invasive candidiasis following treatment were documented.</p> <p>Conclusion</p> <p>Candidal UTI in the NICU population occurs both in term infants with congenital abnormalities and in preterm infants, and is associated with renal parenchymal disease and extra-renal dissemination. A wide variation in clinical approach was documented in this multicenter study. The overall mortality rate in these infants was significant (30%). In one third of the deaths, <it>Candida </it>infection was deemed to be a contributing factor, suggesting the need for antifungal therapy with repeat evaluation for dissemination in infants who are slow to respond to therapy.</p
Simplified Models for LHC New Physics Searches
This document proposes a collection of simplified models relevant to the
design of new-physics searches at the LHC and the characterization of their
results. Both ATLAS and CMS have already presented some results in terms of
simplified models, and we encourage them to continue and expand this effort,
which supplements both signature-based results and benchmark model
interpretations. A simplified model is defined by an effective Lagrangian
describing the interactions of a small number of new particles. Simplified
models can equally well be described by a small number of masses and
cross-sections. These parameters are directly related to collider physics
observables, making simplified models a particularly effective framework for
evaluating searches and a useful starting point for characterizing positive
signals of new physics. This document serves as an official summary of the
results from the "Topologies for Early LHC Searches" workshop, held at SLAC in
September of 2010, the purpose of which was to develop a set of representative
models that can be used to cover all relevant phase space in experimental
searches. Particular emphasis is placed on searches relevant for the first
~50-500 pb-1 of data and those motivated by supersymmetric models. This note
largely summarizes material posted at http://lhcnewphysics.org/, which includes
simplified model definitions, Monte Carlo material, and supporting contacts
within the theory community. We also comment on future developments that may be
useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results
from "Topologies for Early LHC Searches" workshop (SLAC, September 2010).
Supplementary material can be found at http://lhcnewphysics.or
Phenomenology on a Slice of Spacetime
We study the phenomenology resulting from backgrounds of the form , where denotes a generic manifold of
dimension , and is the slice of 5-dimensional anti-de
Sitter space which generates the hierarchy in the Randall-Sundrum (RS) model.
The additional dimensions may be required when the RS model is
embedded into a more fundamental theory. We analyze two classes of
dimensional manifolds: flat and curved geometries. In the first case,
the additional flat dimensions may accommodate localized fermions which in turn
could resolve issues, such as proton decay and flavor, that were not addressed
in the original RS proposal. In the latter case, the positive curvature of an
manifold with can geometrically provide the
5-dimensional warping of the RS model. We demonstrate the key features of these
two classes of models by presenting the background solutions, the spectra of
the Kaluza-Klein (KK) gravitons, and their 4-dimensional couplings, for the
sample manifolds , , and . The resulting phenomenology is
distinct from that of the original RS scenario due to the appearance of a
multitude of new KK graviton states at the weak scale with couplings that are
predicted to be measurably non-universal within the KK tower. In addition, in
the case of flat compactifications, fermion localization can result in KK
graviton and gauge field flavor changing interactions.Comment: 30 pages, 8 figures. Small corrections included to agree with
published versio
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