653 research outputs found
Characteristic discharge and suspended-sediment relationships in two glacier-fed rivers in the Karakoram
The purpose of this thesis is to investigate relationships between meltwater flow and production and flushing of suspended-sediment beneath two alpine glaciers. During the ablation seasons of 1987 and 1988, discrete, hourly measurements were taken of discharge, stage, suspended-sediment concentration and electrical conductivity in two rivers draining catchments of the Bualtar and Batura Glaciers in the Karakoram, N. Pakistan. The discharge time series of the Bualtar River reveals that flow varies over a daily period of three to four weeks, at a diurnal level and over one to four hours. Over all three time scales, electrical conductivity is inversely proportional to discharge suggesting that at high flows, outwash water is derived from surface melt while at low discharges, water originates from subglacial and englacial stores. Variations in suspended-sediment concentration are proportional to discharge at a daily time scale but become less well defined at diurnal and shorter periods. In the Batura River, stage measurements show that diurnal flow variations are superimposed on a longer-term rising limb and have fluctuations over periods of one to four similar to those observed in the Bualtar River in 1987. Conductivity in the Batura River is inversely proportional to discharge. The suspended-sediment concentration record at both sites demonstrates that timing of maximum and minimum sediment flushing over diurnal and shorter periods is not constant with respect to associated flow variations. Investigation of empirical linear regression relationships between flow and sediment transport in both rivers shows that changing hysteresis relationships between variables does not permit adequate prediction of suspended-sediment from discharge. Hence, further development of a deterministic model of subglacial erosion, design by Keeley (1986), is undertaken in order to account for processes of sediment supply and removal at the glacier bed which regression analysis cannot model. Model prediction of variations in suspended-sediment transport in the Bualtar River at the daily level are good suggesting that rates of removal of subglacially eroded bedrock and sediment are directly proportional to discharge variations in arterial conduits. However, short, hourly fluctuations are not simulated well by the model. At this level, sediment accessibility to changing conduit networks within the glacier is more important than subglacial erosion. At a diurnal scale, model performance is variable demonstrating that varying sediment loads in outwash channels are the result of more complex processes of sediment supply and removal than the model accounts for
Algorithms for Highly Symmetric Linear and Integer Programs
This paper deals with exploiting symmetry for solving linear and integer
programming problems. Basic properties of linear representations of finite
groups can be used to reduce symmetric linear programming to solving linear
programs of lower dimension. Combining this approach with knowledge of the
geometry of feasible integer solutions yields an algorithm for solving highly
symmetric integer linear programs which only takes time which is linear in the
number of constraints and quadratic in the dimension.Comment: 21 pages, 1 figure; some references and further comments added, title
slightly change
Applying phylogenomics to understand the emergence of Shiga Toxin producing Escherichia coli O157:H7 strains causing severe human disease in the United Kingdom
Shiga Toxin producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the serotype emerged in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains. In this study the genomes of over 1000 isolates from human clinical cases and cattle, spanning the history of STEC O157:H7 in the United Kingdom were sequenced. Phylogenetic analysis reveals the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimate the time to the most recent common ancestor of the current circulating global clone to 175 years ago, followed by rapid diversification. We show the acquisition of specific virulence determinates occurred relatively recently and coincides with its recent detection in the human population. Using clinical outcome data from 493 cases of STEC O157:H7 we assess the relative risk of severe disease including HUS from each of the defined clades in the population and show the dramatic effect Shiga toxin complement has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years; one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. This work highlights the need to understand the selection pressures maintaining Shiga-toxin encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations
An internet-based intervention with brief nurse support to manage obesity in primary care (POWeR+): a pragmatic, parallel-group, randomised controlled trial
Background
The obesity epidemic has major public health consequences. Expert dietetic and behavioural counselling with intensive follow-up is effective, but resource requirements severely restrict widespread implementation in primary care, where most patients are managed. We aimed to estimate the effectiveness and cost-effectiveness of an internet-based behavioural intervention (POWeR+) combined with brief practice nurse support in primary care.
Methods
We did this pragmatic, parallel-group, randomised controlled trial at 56 primary care practices in central and south England. Eligible adults aged 18 years or older with a BMI of 30 kg/m2 or more (or ≥28 kg/m2 with hypertension, hypercholesterolaemia, or diabetes) registered online with POWeR+—a 24 session, web-based, weight management intervention lasting 6 months. After registration, the website automatically randomly assigned patients (1:1:1), via computer-generated random numbers, to receive evidence-based dietetic advice to swap foods for similar, but healthier, choices and increase fruit and vegetable intake, in addition to 6 monthly nurse follow-up (control group); web-based intervention and face-to-face nurse support (POWeR+Face-to-face [POWeR+F]; up to seven nurse contacts over 6 months); or web-based intervention and remote nurse support (POWeR+Remote [POWeR+R]; up to five emails or brief phone calls over 6 months). Participants and investigators were masked to group allocation at the point of randomisation; masking of participants was not possible after randomisation. The primary outcome was weight loss averaged over 12 months. We did a secondary analysis of weight to measure maintenance of 5% weight loss at months 6 and 12. We modelled the cost-effectiveness of each intervention. We did analysis by intention to treat, with multiple imputation for missing data. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21244703.
Findings
Between Jan 30, 2013, and March 20, 2014, 818 participants were randomly assigned to the control group (n=279), the POWeR+F group (n=269), or the POWeR+R group (n=270). Weight loss averaged over 12 months was recorded in 666 (81%) participants. The control group lost almost 3 kg over 12 months (crude mean weight: baseline 104·38 kg [SD 21·11; n=279], 6 months 101·91 kg [19·35; n=136], 12 months 101·74 kg [19·57; n=227]). The primary imputed analysis showed that compared with the control group, patients in the POWeR+F group achieved an additional weight reduction of 1·5 kg (95% CI 0·6–2·4; p=0·001) averaged over 12 months, and patients in the POWeR+R group achieved an additional 1·3 kg (0·34–2·2; p=0·007). 21% of patients in the control group had maintained a clinically important 5% weight reduction at month 12, compared with 29% of patients in the POWeR+F group (risk ratio 1·56, 0·96–2·51; p=0·070) and 32% of patients in the POWeR+R group (1·82, 1·31–2·74; p=0·004). The incremental overall cost to the health service per kg weight lost with the POWeR+ interventions versus the control strategy was £18 (95% CI −129 to 195) for POWeR+F and –£25 (−268 to 157) for POWeR+R; the probability of being cost-effective at a threshold of £100 per kg lost was 88% and 98%, respectively. No adverse events were reported.
Interpretation
Weight loss can be maintained in some individuals by use of novel written material with occasional brief nurse follow-up. However, more people can maintain clinically important weight reductions with a web-based behavioural program and brief remote follow-up, with no increase in health service costs. Future research should assess the extent to which clinically important weight loss can be maintained beyond 1 year
Low Complexity Regularization of Linear Inverse Problems
Inverse problems and regularization theory is a central theme in contemporary
signal processing, where the goal is to reconstruct an unknown signal from
partial indirect, and possibly noisy, measurements of it. A now standard method
for recovering the unknown signal is to solve a convex optimization problem
that enforces some prior knowledge about its structure. This has proved
efficient in many problems routinely encountered in imaging sciences,
statistics and machine learning. This chapter delivers a review of recent
advances in the field where the regularization prior promotes solutions
conforming to some notion of simplicity/low-complexity. These priors encompass
as popular examples sparsity and group sparsity (to capture the compressibility
of natural signals and images), total variation and analysis sparsity (to
promote piecewise regularity), and low-rank (as natural extension of sparsity
to matrix-valued data). Our aim is to provide a unified treatment of all these
regularizations under a single umbrella, namely the theory of partial
smoothness. This framework is very general and accommodates all low-complexity
regularizers just mentioned, as well as many others. Partial smoothness turns
out to be the canonical way to encode low-dimensional models that can be linear
spaces or more general smooth manifolds. This review is intended to serve as a
one stop shop toward the understanding of the theoretical properties of the
so-regularized solutions. It covers a large spectrum including: (i) recovery
guarantees and stability to noise, both in terms of -stability and
model (manifold) identification; (ii) sensitivity analysis to perturbations of
the parameters involved (in particular the observations), with applications to
unbiased risk estimation ; (iii) convergence properties of the forward-backward
proximal splitting scheme, that is particularly well suited to solve the
corresponding large-scale regularized optimization problem
A Model of Graceful Exit in String Cosmology
We construct, for the first time, a model of graceful exit transition from a
dilaton-driven inflationary phase to a decelerated Friedman-Robertson-Walker
era. Exploiting a demonstration that classical corrections can stabilize a high
curvature string phase while the evolution is still in the weakly coupled
regime, we show that if additional terms of the type that may result from
quantum corrections to the string effective action exist, and induce violation
of the null energy condition, then evolution towards a decelerated
Friedman-Robertson-Walker phase is possible. We also observe that stabilizing
the dilaton at a fixed value, either by capture in a potential minimum or by
radiation production, may require that these quantum corrections are turned
off, perhaps by non-perturbative effects or higher order contributions which
overturn the null energy condition violation.Comment: 17 pages including 9 figures, RevTeX. Uses epsfi
NALP1 is a transcriptional target for cAMP-response-element-binding protein (CREB) in myeloid leukaemia cells
NALP1 (also called DEFCAP, NAC, CARD7) has been shown
to play a central role in the activation of inflammatory caspases
and processing of pro-IL1β (pro-interleukin-1β). Previous studies
showed that NALP1 is highly expressed in peripheral blood
mononuclear cells. In the present study, we report that expression
of NALP1 is absent from CD34+ haematopoietic blast cells,
and its levels are upregulated upon differentiation of CD34+
cells into granulocytes and to a lesser extent into monocytes.
In peripheral blood cells, the highest levels of NALP1 were
observed in CD3+ (T-lymphocytes), CD15+ (granulocytes) and
CD14+ (monocytes) cell populations. Notably, the expression of
NALP1 was significantly increased in the bone marrow blast
cell population of some patients with acute leukaemia, but not
among tissue samples from thyroid and renal cancer. A search for
consensus sites within the NALP1 promoter revealed a sequence
for CREB (cAMP-response-element-binding protein) that was
required for transcriptional activity. Moreover, treatment of TF1
myeloid leukaemia cells with protein kinase C and protein kinase
A activators induced CREB phosphorylation and upregulated
the mRNA and protein levels of NALP1. Conversely, ectopic
expression of a dominant negative form of CREB in TF1 cells
blocked the transcriptional activity of the NALP1 promoter and
significantly reduced the expression of NALP1. Thus NALP1
is transcriptionally regulated by CREB in myeloid cells, a
mechanism that may contribute to modulate the response of these
cells to pro-inflammatory stimuli
A comparison of balloon injury models of endovascular lesions in rat arteries
BACKGROUND: Balloon injury (BI) of the rat carotid artery (CCA) is widely
used to study intimal hyperplasia (IH) and decrease in lumen diameter
(LD), but CCA's small diameter impedes the evaluation of endovascular
therapies. Therefore, we validated BI in the aorta (AA) and iliac artery
(CIA) to compare it with CCA. METHODS: Rats underwent BI or a sham
procedure (control). Light microscopic evaluation was performed either
directly or at 1, 2, 3, 4 and 16 weeks follow-up. The area of IH and the
change in LD (LD at 16 weeks minus LD post BI) were compared. RESULTS: In
the BI-groups the area of IH increased to 0.14 +/- 0.08 mm2 (CCA), 0.14
+/- 0.03 mm2 (CIA) and 0.12 +/- 0.04 mm2 (AA) at 16 weeks (NS). The LD
decreased with 0.49 +/- 0.07 mm (CCA), compared to 0.22 +/- 0.07 mm (CIA)
and 0.07 +/- 0.10 mm (AA) at 16 weeks (p < 0.05). The constrictive
vascular remodelling (CVR = wall circumference loss combined with a
decrease in LD) was -0.17 +/- 0.05 mm in CIA but absent in CCA and AA. No
IH, no decrease in LD and no CVR was seen in the control groups.
CONCLUSIONS: BI resulted in: (1.) a decrease in LD in CCA due to IH, (2.)
a decrease in LD in CIA due to IH and CVR, (3.) no change in LD in AA,
(4.) Comparable IH development in all arteries, (5.) CCA has no vasa
vasorum compared to CIA and AA, (6.) The CIA model combines good access
for 2 F endovascular catheters with a decrease in LD due to IH and CVR
after BI
Monte Carlo reconstruction of the inflationary potential
We present Monte Carlo reconstruction, a new method for ``inverting''
observational data to constrain the form of the scalar field potential
responsible for inflation. This stochastic technique is based on the flow
equation formalism and has distinct advantages over reconstruction methods
based on a Taylor expansion of the potential. The primary ansatz required for
Monte Carlo reconstruction is simply that inflation is driven by a single
scalar field. We also require a very mild slow roll constraint, which can be
made arbitrarily weak since Monte Carlo reconstruction is implemented at
arbitrary order in the slow roll expansion. While our method cannot evade
fundamental limits on the accuracy of reconstruction, it can be simply and
consistently applied to poor data sets, and it takes advantage of the attractor
properties of single-field inflation models to constrain the potential outside
the small region directly probed by observations. We show examples of Monte
Carlo reconstruction for data sets similar to that expected from the Planck
satellite, and for a hypothetical measurement with a factor of five better
parameter discrimination than Planck.Comment: 10 pages, 5 figures (RevTeX 4) Version submitted to PRD: references
added, minor clarification
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