Healthcare Resource Utilization Among Patients in England with Systemic Sclerosis-Associated Interstitial Lung Disease: A Retrospective Database Analysis

Introduction Systemic sclerosis-associated interstitial lung disease (SSc-ILD) places a substantial burden on patients and healthcare systems. The objectives of this study were to describe clinical characteristics and assess healthcare resource utilization and costs of patients with SSc-ILD in England, compared with patients with non-pulmonary organ involvement related to SSc (SSc-OOI). Methods This population-based retrospective study used data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics. Data were extracted from medical records dated January 1, 2005 to March 31, 2016. Patients with SSc were identified and placed in subgroups based on organ involvement: SSc-ILD, SSc-OOI, and both (SSc-ILD-OOI). Patients with SSc-ILD-OOI were included in both the SSc-ILD and SSc-OOI subgroups. All-cause healthcare costs, excluding medication costs, were calculated to 2016 British pounds sterling (£). Results This study included 675 patients with SSc: 174 (26%) had neither ILD nor other organ involvement (OOI); 127 (19%) had SSc-ILD; 477 (71%) had SSc-OOI; 103 (15%) had SSc-ILD-OOI. Age-weighted median [interquartile range (IQR)] annual healthcare costs per patient were: £1496 (£664–£2817) in SSc only; £6375 (£3451–£15,041) in SSc-ILD; £4084 (£1454–£10,105) in SSc-OOI; £6632 (£4023–£17,009) in SSc-ILD-OOI. In multivariate analysis, older age at diagnosis, diagnosis of anemia, and number of comorbid diseases were associated with higher yearly healthcare costs. Conclusion The annual healthcare cost for patients with SSc-ILD is substantial, and higher than that of patients with SSc-OOI or SSc only. These results quantify the economic burden of SSc-ILD in a real-world setting, and highlight the need for treatment of this disease

Multi-objective optimization of RF circuit blocks via surrogate models and NBI and SPEA2 methods

Multi-objective optimization techniques can be categorized globally into deterministic and evolutionary methods. Examples of such methods are the Normal Boundary Intersection (NBI) method and the Strength Pareto Evolutionary Algorithm (SPEA2), respectively. With both methods one explores trade-offs between conflicting performances. Surrogate models can replace expensive circuit simulations so enabling faster computation of circuit performances. As surrogate models of behavioral parameters and performance outcomes, we consider look-up tables with interpolation and Neural Network models

Tunable Emergent Heterostructures in a Prototypical Correlated Metal

At the interface between two distinct materials desirable properties, such as superconductivity, can be greatly enhanced, or entirely new functionalities may emerge. Similar to in artificially engineered heterostructures, clean functional interfaces alternatively exist in electronically textured bulk materials. Electronic textures emerge spontaneously due to competing atomic-scale interactions, the control of which, would enable a top-down approach for designing tunable intrinsic heterostructures. This is particularly attractive for correlated electron materials, where spontaneous heterostructures strongly affect the interplay between charge and spin degrees of freedom. Here we report high-resolution neutron spectroscopy on the prototypical strongly-correlated metal CeRhIn5, revealing competition between magnetic frustration and easy-axis anisotropy -- a well-established mechanism for generating spontaneous superstructures. Because the observed easy-axis anisotropy is field-induced and anomalously large, it can be controlled efficiently with small magnetic fields. The resulting field-controlled magnetic superstructure is closely tied to the formation of superconducting and electronic nematic textures in CeRhIn5, suggesting that in-situ tunable heterostructures can be realized in correlated electron materials

Silicon-based spin and charge quantum computation

Silicon-based quantum-computer architectures have attracted attention because of their promise for scalability and their potential for synergetically utilizing the available resources associated with the existing Si technology infrastructure. Electronic and nuclear spins of shallow donors (e.g. phosphorus) in Si are ideal candidates for qubits in such proposals due to the relatively long spin coherence times. For these spin qubits, donor electron charge manipulation by external gates is a key ingredient for control and read-out of single-qubit operations, while shallow donor exchange gates are frequently invoked to perform two-qubit operations. More recently, charge qubits based on tunnel coupling in P$_2^+$ substitutional molecular ions in Si have also been proposed. We discuss the feasibility of the building blocks involved in shallow donor quantum computation in silicon, taking into account the peculiarities of silicon electronic structure, in particular the six degenerate states at the conduction band edge. We show that quantum interference among these states does not significantly affect operations involving a single donor, but leads to fast oscillations in electron exchange coupling and on tunnel-coupling strength when the donor pair relative position is changed on a lattice-parameter scale. These studies illustrate the considerable potential as well as the tremendous challenges posed by donor spin and charge as candidates for qubits in silicon.Comment: Review paper (invited) - to appear in Annals of the Brazilian Academy of Science

Aryl hydrocarbon receptor nuclear translocator (ARNT) gene as a positional and functional candidate for type 2 diabetes and prediabetic intermediate traits: Mutation detection, case-control studies, and gene expression analysis

<p>Abstract</p> <p>Background</p> <p>ARNT, a member of the basic helix-loop-helix family of transcription factors, is located on human chromosome 1q21–q24, a region which showed well replicated linkage to type 2 diabetes. We hypothesized that common polymorphisms in the <it>ARNT </it>gene might increase the susceptibility to type 2 diabetes through impaired glucose-stimulated insulin secretion.</p> <p>Methods</p> <p>We selected 9 single nucleotide polymorphisms to tag common variation across the <it>ARNT </it>gene. Additionally we searched for novel variants in functional coding domains in European American and African American samples. Case-control studies were performed in 191 European American individuals with type 2 diabetes and 187 nondiabetic European American control individuals, and in 372 African American individuals with type 2 diabetes and 194 African American control individuals. Metabolic effects of <it>ARNT </it>variants were examined in 122 members of 26 European American families from Utah and in 225 unrelated individuals from Arkansas. Gene expression was tested in 8 sibling pairs discordant for type 2 diabetes.</p> <p>Results</p> <p>No nonsynonymous variants or novel polymorphisms were identified. No SNP was associated with type 2 diabetes in either African Americans or European Americans, but among nondiabetic European American individuals, <it>ARNT </it>SNPs rs188970 and rs11204735 were associated with acute insulin response (AIR_g; p =< 0.005). SNP rs2134688 interacted with body mass index to alter β-cell compensation to insulin resistance (disposition index; p = 0.004). No significant difference in <it>ARNT </it>mRNA levels was observed in transformed lymphocytes from sibling pairs discordant for type 2 diabetes.</p> <p>Conclusion</p> <p>Common <it>ARNT </it>variants are unlikely to explain the linkage signal on chromosome 1q, but may alter insulin secretion in nondiabetic subjects. Our studies cannot exclude a role for rare variants or variants of small (< 1.6) effect size.</p

A patient with metastatic melanoma presenting with gastrointestinal perforation after dacarbazine infusion: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report a rare case of gastrointestinal perforation following dacarbazine infusion for metastatic melanoma. The condition is attributed to a responding malignant melanoma in the gastrointestinal tract.</p> <p>Case presentation</p> <p>A 52-year-old Caucasian man presented with abdominal pain and distension, malaise, night sweats, dysphagia and early satiety. A computed tomography scan showed massive ascites, lymphadenopathy and liver lesions suspect for metastases. An upper gastrointestinal endoscopy was performed and revealed multiple dark lesions of 5 mm to 10 mm in his stomach and duodenum.</p> <p>When his skin was re-examined, an irregular pigmented lesion over the left clavicle measuring 15 mm × 8 mm with partial depigmentation was found. Histological examination of a duodenal lesion was consistent with a diagnosis of metastatic melanoma. The patient deteriorated and his level of lactate dehydrogenase rapidly increased. The patient was started on systemic treatment with dacarbazine 800 mg/m²every three weeks and he was discharged one day after the first dose. On the sixth day he was readmitted with severe abdominal pain. A chest X-ray showed the presence of free intraperitoneal air that was consistent with gastrointestinal perforation. His lactate dehydrogenase level had fallen from 6969U/L to 1827U/L, supporting the conclusion that the response of gastrointestinal metastases to dacarbazine had resulted in the perforation of the patient's bowel wall. A laparotomy was discussed with the patient and his family but he decided to go home with symptomatic treatment. He died 11 days later.</p> <p>Conclusion</p> <p>Melanoma can originate in, as well as metastasize to, the gastrointestinal tract. Gastrointestinal perforations due to responding tumors are a well-known complication of systemic treatment of gastrointestinal lymphomas. However, as the response rate of metastatic melanoma to dacarbazine is only 10% to 20%, and responses are usually only partial, perforation due to treatment response in metastatic melanoma is rare.</p> <p>Medical oncologists should be aware of the risk of bowel perforation after starting cytotoxic chemotherapy on patients with gastrointestinal metastases.</p

A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio

Global patterns of body size evolution in squamate reptiles are not driven by climate

Aim: Variation in body size across animal species underlies most ecological and evolutionary processes shaping local- and large-scale patterns of biodiversity. For well over a century, climatic factors have been regarded as primary sources of natural selection on animal body size, and hypotheses such as Bergmann's rule (the increase of body size with decreasing temperature) have dominated discussions. However, evidence for consistent climatic effects, especially among ectotherms, remains equivocal. Here, we test a range of key hypotheses on climate-driven size evolution in squamate reptiles across several spatial and phylogenetic scales. Location: Global. Time period: Extant. Major taxa studied: Squamates (lizards and snakes). Methods: We quantified the role of temperature, precipitation, seasonality and net primary productivity as drivers of body mass across ca. 95% of extant squamate species (9,733 spp.). We ran spatial autoregressive models of phylogenetically corrected median mass per equal-area grid cell. We ran models globally, across separate continents and for major squamate clades independently. We also performed species-level analyses using phylogenetic generalized least square models and linear regressions of independent contrasts of sister species. Results: Our analyses failed to identify consistent spatial patterns in body size as a function of our climatic predictors. Nearly all continent- and family-level models differed from one another, and species-level models had low explanatory power. Main conclusions: The global distribution of body mass among living squamates varies independently from the variation in multiple components of climate. Our study, the largest in spatial and taxonomic scale conducted to date, reveals that there is little support for a universal, consistent mechanism of climate-driven size evolution within squamates

Dynamics and transport near quantum-critical points

The physics of non-zero temperature dynamics and transport near quantum-critical points is discussed by a detailed study of the O(N)-symmetric, relativistic, quantum field theory of a N-component scalar field in $d$ spatial dimensions. A great deal of insight is gained from a simple, exact solution of the long-time dynamics for the N=1 d=1 case: this model describes the critical point of the Ising chain in a transverse field, and the dynamics in all the distinct, limiting, physical regions of its finite temperature phase diagram is obtained. The N=3, d=1 model describes insulating, gapped, spin chain compounds: the exact, low temperature value of the spin diffusivity is computed, and compared with NMR experiments. The N=3, d=2,3 models describe Heisenberg antiferromagnets with collinear N\'{e}el correlations, and experimental realizations of quantum-critical behavior in these systems are discussed. Finally, the N=2, d=2 model describes the superfluid-insulator transition in lattice boson systems: the frequency and temperature dependence of the the conductivity at the quantum-critical coupling is described and implications for experiments in two-dimensional thin films and inversion layers are noted.Comment: Lectures presented at the NATO Advanced Study Institute on "Dynamical properties of unconventional magnetic systems", Geilo, Norway, April 2-12, 1997, edited by A. Skjeltorp and D. Sherrington, Kluwer Academic, to be published. 46 page