Large distance expansion of Mutual Information for disjoint disks in a free scalar theory

We compute the next-to-leading order term in the long-distance expansion of the mutual information for free scalars in three space-time dimensions. The geometry considered is two disjoint disks separated by a distance $r$ between their centers. No evidence for non-analyticity in the R\'enyi parameter $n$ for the continuation $n \rightarrow 1$ in the next-to-leading order term is found.Comment: 15 pages, This version contains few extra references, some technical material has been move to appendices, and other minor modifications to match with the version accepted for publicatio

Miniature High-Force, Long-Stroke SMA Linear Actuators

Improved long-stroke shape-memory-alloy (SMA) linear actuators are being developed to exert significantly higher forces and operate at higher activation temperatures than do prior SMA actuators. In these actuators, long linear strokes are achieved through the principle of displacement multiplication, according to which there are multiple stages, each intermediate stage being connected by straight SMA wire segments to the next stage so that relative motions of stages are additive toward the final stage, which is the output stage. Prior SMA actuators typically include polymer housings or shells, steel or aluminum stages, and polymer pads between successive stages of displacement-multiplication assemblies. Typical output forces of prior SMA actuators range from 10 to 20 N, and typical strokes range from 0.5 to 1.5 cm. An important disadvantage of prior SMA wire actuators is relatively low cycle speed, which is related to actuation temperature as follows: The SMA wires in prior SMA actuators are typically made of a durable nickel/titanium alloy that has a shape-memory activation temperature of 80 C. An SMA wire can be heated quickly from below to above its activation temperature to obtain a stroke in one direction, but must then be allowed to cool to somewhat below its activation temperature (typically, less than or equal to 60 C in the case of an activation temperature of 80 C) to obtain a stroke in the opposite direction (return stroke). At typical ambient temperatures, cooling times are of the order of several seconds. Cooling times thus limit cycle speeds. Wires made of SMA alloys having significantly higher activation temperatures [denoted ultra-high-temperature (UHT) SMA alloys] cool to the required lower return-stroke temperatures more rapidly, making it possible to increase cycle speeds. The present development is motivated by a need, in some applications (especially aeronautical and space-flight applications) for SMA actuators that exert higher forces, operate at greater cycle speeds, and have stronger housings that can withstand greater externally applied forces and impacts. The main novel features of the improved SMA actuators are the following: 1) The ends of the wires are anchored in compact crimps made from short steel tubes. Each wire end is inserted in a tube, the tube is flattened between planar jaws to make the tube grip the wire, the tube is compressed to a slight U-cross-section deformation to strengthen the grip, then the crimp is welded onto one of the actuator stages. The pull strength of a typical crimp is about 125 N -- comparable to the strength of the SMA wire and greater than the typical pull strengths of wire-end anchors in prior SMA actuators. Greater pull strength is one of the keys to achievement of higher actuation force; 2) For greater strength and resistance to impacts, housings are milled from aluminum instead of being made from polymers. Each housing is made from two pieces in a clamshell configuration. The pieces are anodized to reduce sliding friction; 3) Stages are made stronger (to bear greater compression loads without excessive flexing) by making them from steel sheets thicker than those used in prior SMA actuators. The stages contain recessed pockets to accommodate the crimps. Recessing the pockets helps to keep overall dimensions as small as possible; and, 4) UHT SMA wires are used to satisfy the higher-speed/higher-temperature requirement

The economic implications of HLA matching in cadaveric renal transplantation.

Abstract Background: The potential economic effects of the allocation of cadaveric kidneys on the basis of tissue-matching criteria are controversial. We analyzed the economic costs associated with the transplantation of cadaveric kidneys with various numbers of HLA mismatches and examined the potential economic benefits of a local, as compared with a national, system designed to minimize HLA mismatches between donor and recipient in first cadaveric renal transplantations. Methods: All data were supplied by the U.S. Renal Data System. Data on all payments made by Medicare from 1991 through 1997 for the care of recipients of a first cadaveric renal transplant were analyzed according to the number of HLA-A, B, and DR mismatches between donor and recipient and the duration of cold ischemia before transplantation. Results: Average Medicare payments for renal-transplant recipients in the three years after transplantation increased from $60,436 per patient for fully HLA-matched kidneys (those with no HLA-A, B, or DR mismatches) to$80,807 for kidneys with six HLA mismatches between donor and recipient, a difference of 34 percent (P\u3c0.001). By three years after transplantation, the average Medicare payments were $64,119 for transplantations of kidneys with less than 12 hours of cold-ischemia time and$74,997 for those with more than 36 hours (P\u3c0.001). In simulations, the assignment of cadaveric kidneys to recipients by a method that minimized HLA mismatching within a local geographic area (i.e., within one of the approximately 50 organ-procurement organizations, which cover widely varying geographic areas) produced the largest cost savings ($4,290 per patient over a period of three years) and the largest improvements in the graft-survival rate (2.3 percent) when the potential costs of longer cold-ischemia time were considered. Conclusions: Transplantation of better-matched cadaveric kidneys could have substantial economic advantages. In our simulations, HLA-based allocation of kidneys at the local level produced the largest estimated cost savings, when the duration of cold ischemia was taken into account. No additional savings were estimated to result from a national allocation program, because the additional costs of longer cold-ischemia time were greater than the advantages of optimizing HLA matching

Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery

Characterizing the gut microbiome in trauma: significant changes in microbial diversity occur early after severe injury.

Background:Recent studies have demonstrated the vital influence of commensal microbial communities on human health. The central role of the gut in the response to injury is well described; however, no prior studies have used culture-independent profiling techniques to characterize the gut microbiome after severe trauma. We hypothesized that in critically injured patients, the gut microbiome would undergo significant compositional changes in the first 72 hours after injury. Methods:Trauma stool samples were prospectively collected via digital rectal examination at the time of presentation (0 hour). Patients admitted to the intensive care unit (n=12) had additional stool samples collected at 24 hours and/or 72 hours. Uninjured patients served as controls (n=10). DNA was extracted from stool samples and 16S rRNA-targeted PCR amplification was performed; amplicons were sequenced and binned into operational taxonomic units (OTUs; 97% sequence similarity). Diversity was analyzed using principle coordinates analyses, and negative binomial regression was used to determine significantly enriched OTUs. Results:Critically injured patients had a median Injury Severity Score of 27 and suffered polytrauma. At baseline (0 hour), there were no detectable differences in gut microbial community diversity between injured and uninjured patients. Injured patients developed changes in gut microbiome composition within 72 hours, characterized by significant alterations in phylogenetic composition and taxon relative abundance. Members of the bacterial orders Bacteroidales, Fusobacteriales and Verrucomicrobiales were depleted during 72 hours, whereas Clostridiales and Enterococcus members enriched significantly. Discussion:In this initial study of the gut microbiome after trauma, we demonstrate that significant changes in phylogenetic composition and relative abundance occur in the first 72 hours after injury. This rapid change in intestinal microbiota represents a critical phenomenon that may influence outcomes after severe trauma. A better understanding of the nature of these postinjury changes may lead to the ability to intervene in otherwise pathological clinical trajectories. Level of evidence:III. Study type:Prognostic/epidemiological

Chemical evolution of the Galactic bulge as traced by microlensed dwarf and subgiant stars. II. Ages, metallicities, detailed elemental abundances, and connections to the Galactic thick disc

The Bulge is the least understood major stellar population of the Milky Way. Most of what we know about the formation and evolution of the Bulge comes from bright giant stars. The underlying assumption that giants represent all the stars, and accurately trace the chemical evolution of a stellar population, is under debate. In particular, recent observations of a few microlensed dwarf stars give a very different picture of the evolution of the Bulge from that given by the giant stars. [ABRIDGED] We perform a detailed elemental abundance analysis of dwarf stars in the Galactic bulge, based on high-resolution spectra that were obtained while the stars were optically magnified during gravitational microlensing events. [ABRIDGED] We present detailed elemental abundances and stellar ages for six new dwarf stars in the Galactic bulge. Combining these with previous events, here re-analysed with the same methods, we study a homogeneous sample of 15 stars, which constitute the largest sample to date of microlensed dwarf stars in the Galactic bulge. We find that the stars span the full range of metallicities from [Fe/H]=-0.72 to +0.54, and an average metallicity of =-0.08+/-0.47, close to the average metallicity based on giant stars in the Bulge. Furthermore, the stars follow well-defined abundance trends, that for [Fe/H]<0 are very similar to those of the local Galactic thick disc. This suggests that the Bulge and the thick disc have had, at least partially, comparable chemical histories. At sub-solar metallicities we find the Bulge dwarf stars to have consistently old ages, while at super-solar metallicities we find a wide range of ages. Using the new age and abundance results from the microlensed dwarf stars we investigate possible formation scenarios for the Bulge.Comment: New version accepted for publication in Astronomy and Astrophysic

Therapy optimization in multiple sclerosis: a prospective observational study of therapy compliance and outcomes.

BACKGROUND: Data sources for MS research are numerous but rarely provide an objective measure of drug therapy compliance coupled with patient-reported health outcomes. The objective of this paper is to describe the methods and baseline characteristics of the Therapy Optimization in MS (TOP MS) study designed to investigate the relationship between disease-modifying therapy compliance and health outcomes. METHODS: TOP MS was designed as a prospective, observational, nationwide patient-focused study using an internet portal for data entry. The protocol was reviewed and approved by Sterling IRB. The study was registered with ClinicalTrials.gov. It captured structured survey data monthly from MS patients recruited by specialty pharmacies. Data collection included the clinical characteristics of MS such as MS relapses. Disability, quality of life and work productivity and activity impairment were assessed quarterly with well-validated scales. When events like severe fatigue or new or worsening depression were reported, feedback was provided to treating physicians. The therapy compliance measure was derived from pharmacy drug shipment records uploaded to the study database. The data presented in this paper use descriptive statistics. RESULTS: The TOP MS Study enrolled 2966 participants receiving their disease-modifying therapy (DMT) from specialty pharmacies. The mean age of the sample was 49 years, 80.4% were female, 89.9% were Caucasian and 55.7% were employed full or part time. Mean time since first symptoms was 11.5 years; mean duration since diagnosis was 9.5 years. Patient-reported EDSS was 3.5; 72.2% had a relapsing-remitting disease course. The most commonly reported symptoms at the time of enrollment were fatigue (74.7%), impaired coordination or balance (61.8%) and numbness and tingling (61.2%). Half of the sample was using glatiramer acetate and half was using beta-interferons. CONCLUSION: Demographic and clinical characteristics of the TOP MS sample at enrollment are consistent with other community-based MS samples, and the sample appears to be representative of DMT users in the US. TOP MS data can be used to explore the associations between disease-modifying therapy compliance and health outcomes. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00819000)

Chemical Composition of Faint (I~21 mag) Microlensed Bulge Dwarf OGLE-2007-BLG-514S

We present a high-resolution spectrum of a microlensed G dwarf in the Galactic bulge with spectroscopic temperature T_eff = 5600 +/- 180 K. This I~21 mag star was magnified by a factor ranging from 1160 to 1300 at the time of observation. Its high metallicity ([Fe/H] = 0.33 +/- 0.15) places this star at the upper end of the bulge giant metallicity distribution. Using a K-S test, we find a 1.6% probability that the published microlensed bulge dwarfs share an underlying distribution with bulge giants, properly accounting for a radial bulge metallicity gradient. We obtain abundance measurements for 15 elements and perform a rigorous error analysis that includes covariances between parameters. This star, like bulge giants with the same metallicity, shows no alpha enhancement. It confirms the chemical abundance trends observed in previously analyzed bulge dwarfs. At supersolar metallicities, we observe a discrepancy between bulge giant and bulge dwarf Na abundances.Comment: 13 pages, 8 figures, 5 tables, submitted to Ap

Mechanochemical action of the dynamin protein

Dynamin is a ubiquitous GTPase that tubulates lipid bilayers and is implicated in many membrane severing processes in eukaryotic cells. Setting the grounds for a better understanding of this biological function, we develop a generalized hydrodynamics description of the conformational change of large dynamin-membrane tubes taking into account GTP consumption as a free energy source. On observable time scales, dissipation is dominated by an effective dynamin/membrane friction and the deformation field of the tube has a simple diffusive behavior, which could be tested experimentally. A more involved, semi-microscopic model yields complete predictions for the dynamics of the tube and possibly accounts for contradictory experimental results concerning its change of conformation as well as for plectonemic supercoiling.Comment: 17 pages, 4 figures; typos corrected, reference adde