1,263 research outputs found
Asymmetric simple exclusion process in one-dimensional chains with long-range links
We study the boundary-driven asymmetric simple exclusion process (ASEP) in a
one-dimensional chain with long-range links. Shortcuts are added to a chain by
connecting different pairs of sites selected randomly where and
denote the chain length and the shortcut density, respectively. Particles flow
into a chain at one boundary at rate and out of a chain at the other
boundary at rate , while they hop inside a chain via nearest-neighbor
bonds and long-range shortcuts. Without shortcuts, the model reduces to the
boundary-driven ASEP in a one-dimensional chain which displays the low density,
high density, and maximal current phases. Shortcuts lead to a drastic change.
Numerical simulation studies suggest that there emerge three phases; an empty
phase with , a jammed phase with , and a shock phase
with where is the mean particle density. The shock phase is
characterized with a phase separation between an empty region and a jammed
region with a localized shock between them. The mechanism for the shock
formation and the non-equilibrium phase transition is explained by an analytic
theory based on a mean-field approximation and an annealed approximation.Comment: revised version (16 pages and 6 eps figures
Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival.
Condensates formed by prion-like low-complexity domains have small-world network structures and interfaces defined by expanded conformations
Biomolecular condensates form via coupled associative and segregative phase transitions of multivalent associative macromolecules. Phase separation coupled to percolation is one example of such transitions. Here, we characterize molecular and mesoscale structural descriptions of condensates formed by intrinsically disordered prion-like low complexity domains (PLCDs). These systems conform to sticker-and-spacers architectures. Stickers are cohesive motifs that drive associative interactions through reversible crosslinking and spacers affect the cooperativity of crosslinking and overall macromolecular solubility. Our computations reproduce experimentally measured sequence-specific phase behaviors of PLCDs. Within simulated condensates, networks of reversible inter-sticker crosslinks organize PLCDs into small-world topologies. The overall dimensions of PLCDs vary with spatial location, being most expanded at and preferring to be oriented perpendicular to the interface. Our results demonstrate that even simple condensates with one type of macromolecule feature inhomogeneous spatial organizations of molecules and interfacial features that likely prime them for biochemical activity
Uncovering Extreme Nonlinear Dynamics in Solids Through Time-Domain Field Analysis
Time-domain analysis of harmonic fields with sub-cycle resolution is now
experimentally viable due to the emergence of sensitive, on-chip techniques for
petahertz-scale optical-field sampling. We demonstrate how such a time-domain,
field-resolved analysis uncovers the extreme nonlinear electron dynamics
responsible for high-harmonic generation within solids. Time-dependent density
functional theory was used to simulate harmonic generation from a solid-state
band-gap system driven by near- to mid-infrared waveforms. Particular attention
was paid to regimes where both intraband and interband emission mechanisms play
a critical role in shaping the nonlinear response. We show that a time-domain
analysis of the harmonic radiation fields identifies the interplay between
intra- and interband dynamical processes underlying the nonlinear light
generation. With further analysis, we show that changes to the dominant
emission regime can occur after only slight changes to the peak driving
intensity and central driving wavelength. Time-domain analysis of harmonic
fields also reveals, for the first time, the possibility of rapid changes in
the dominant emission mechanism within the temporal window of the driving pulse
envelope. Finally, we examine the experimental viability of performing
time-domain analysis of harmonic fields with sub-cycle resolution using
realistic parameters
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
Orientifolds and the Refined Topological String
We study refined topological string theory in the presence of orientifolds by
counting second-quantized BPS states in M-theory. This leads us to propose a
new integrality condition for both refined and unrefined topological strings
when orientifolds are present. We define the SO(2N) refined Chern-Simons theory
which computes refined open string amplitudes for branes wrapping Seifert
three-manifolds. We use the SO(2N) refined Chern-Simons theory to compute new
invariants of torus knots that generalize the Kauffman polynomials. At large N,
the SO(2N) refined Chern-Simons theory on the three-sphere is dual to refined
topological strings on an orientifold of the resolved conifold, generalizing
the Gopakumar-Sinha-Vafa duality. Finally, we use the (2,0) theory to define
and solve refined Chern-Simons theory for all ADE gauge groups
Survival outcomes of patients with primary plasma cell leukemia (pPCL) treated with novel agents
Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma
Lenalidomide-dexamethasone improved outcome in newly diagnosed elderly multiple
myeloma patients. We randomly assigned 662 patients who were age \u202165 years or
transplantation-ineligible to receive induction with melphalan-prednisone-lenalidomide
(MPR) or cyclophosphamide-prednisone-lenalidomide (CPR) or lenalidomide plus lowdose
dexamethasone (Rd). The primary end point was progression-free survival (PFS) in
triplet (MPR and CPR) vs doublet (Rd) lenalidomide-containing regimens. After a median
follow-up of 39 months, the medianPFSwas22 months for the triplet combinations and 21
months for the doublet (P 5 .284). The median overall survival (OS) was not reached in
either arms, and the 4-year OS was 67% for the triplet and 58% for the doublet arms (P 5 .709). By considering the 3 treatment arms
separately, no difference in outcome was detected among MPR, CPR, and Rd. The most common grade \u20213 toxicity was neutropenia:
64% in MPR, 29% in CPR, and 25% in Rd patients (P < .0001). Grade \u20213 nonhematologic toxicities were similar among arms and were
mainly infections (6.5% to 11%), constitutional (3.5% to 9.5%), and cardiac (4.5% to 6%), with no difference among the arms. In
conclusion, in the overall population, the alkylator-containing tripletsMPRandCPRwere not superior to the alkylator-free doublet Rd,
which was associated with lower toxicit
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