Patient-reported utilities in advanced or metastatic melanoma, including analysis of utilities by time to death

Background: Health-related quality of life is often collected in clinical studies, and forms a cornerstone of economic evaluation. This study had two objectives, firstly to report and compare pre- and post-progression health state utilities in advanced melanoma when valued by different methods and secondly to explore the validity of progression-based health state utility modelling compared to modelling based upon time to death. Methods: Utilities were generated from the ipilimumab MDX010-20 trial (Clinicaltrials.gov Identifier: NCT00094653) using the condition-specific EORTC QLQ-C30 (via the EORTC-8D) and generic SF-36v2 (via the SF-6D) preference-based measures. Analyses by progression status and time to death were conducted on the patient-level data from the MDX010-20 trial using generalised estimating equations fitted in Stata®, and the predictive abilities of the two approaches compared. Results: Mean utility showed a decrease on disease progression in both the EORTC-8D (0.813 to 0.776) and the SF-6D (0.648 to 0.626). Whilst higher utilities were obtained using the EORTC-8D, the relative decrease in utility on progression was similar between measures. When analysed by time to death, both EORTC-8D and SF-6D showed a large decrease in utility in the 180 days prior to death (from 0.831 to 0.653 and from 0.667 to 0.544, respectively). Compared to progression status alone, the use of time to death gave similar or better estimates of the original data when used to predict patient utility in the MDX010-20 study. Including both progression status and time to death further improved model fit. Utilities seen in MDX010-20 were also broadly comparable with those seen in the literature. Conclusions: Patient-level utility data should be analysed prior to constructing economic models, as analysis solely by progression status may not capture all predictive factors of patient utility and time to death may, as death approaches, be as or more important. Additionally this study adds to the body of evidence showing that different scales lead to different health state values. Further research is needed on how different utility instruments (the SF-6D, EORTC-8D and EQ-5D) relate to each other in different disease areas

Analysis of Localization Phenomena in Weakly Interacting Disordered Lattice Gases

Disorder plays a crucial role in many systems particularly in solid state physics. However, the disorder in a particular system can usually not be chosen or controlled. We show that the unique control available for ultracold atomic gases may be used for the production and observation of disordered quantum degenerate gases. A detailed analysis of localization effects for two possible realizations of a disordered potential is presented. In a theoretical analysis clear localization effects are observed when a superlattice is used to provide a quasiperiodic disorder. The effects of localization are analyzed by investigating the superfluid fraction and the localization length within the system. The theoretical analysis in this paper paves a clear path for the future observation of Anderson-like localization in disordered quantum gases.Comment: 9 pages, 13 figure

Mean-field phase diagram of disordered bosons in a lattice at non-zero temperature

Bosons in a periodic lattice with on-site disorder at low but non-zero temperature are considered within a mean-field theory. The criteria used for the definition of the superfluid, Mott insulator and Bose glass are analysed. Since the compressibility does never vanish at non-zero temperature, it can not be used as a general criterium. We show that the phases are unambiguously distinguished by the superfluid density and the density of states of the low-energy exitations. The phase diagram of the system is calculated. It is shown that even a tiny temperature leads to a significant shift of the boundary between the Bose glass and superfluid

An enigmatic fourth runt domain gene in the fugu genome: ancestral gene loss versus accelerated evolution

BACKGROUND: The runt domain transcription factors are key regulators of developmental processes in bilaterians, involved both in cell proliferation and differentiation, and their disruption usually leads to disease. Three runt domain genes have been described in each vertebrate genome (the RUNX gene family), but only one in other chordates. Therefore, the common ancestor of vertebrates has been thought to have had a single runt domain gene. RESULTS: Analysis of the genome draft of the fugu pufferfish (Takifugu rubripes) reveals the existence of a fourth runt domain gene, FrRUNT, in addition to the orthologs of human RUNX1, RUNX2 and RUNX3. The tiny FrRUNT packs six exons and two putative promoters in just 3 kb of genomic sequence. The first exon is located within an intron of FrSUPT3H, the ortholog of human SUPT3H, and the first exon of FrSUPT3H resides within the first intron of FrRUNT. The two gene structures are therefore "interlocked". In the human genome, SUPT3H is instead interlocked with RUNX2. FrRUNT has no detectable ortholog in the genomes of mammals, birds or amphibians. We consider alternative explanations for an apparent contradiction between the phylogenetic data and the comparison of the genomic neighborhoods of human and fugu runt domain genes. We hypothesize that an ancient RUNT locus was lost in the tetrapod lineage, together with FrFSTL6, a member of a novel family of follistatin-like genes. CONCLUSIONS: Our results suggest that the runt domain family may have started expanding in chordates much earlier than previously thought, and exemplify the importance of detailed analysis of whole-genome draft sequence to provide new insights into gene evolution

Mapping the disease-specific LupusQoL to the SF-6D

Purpose To derive a mapping algorithm to predict SF-6D utility scores from the non-preference-based LupusQoL and test the performance of the developed algorithm on a separate independent validation data set. Method LupusQoL and SF-6D data were collected from 320 patients with systemic lupus erythematosus (SLE) attending routine rheumatology outpatient appointments at seven centres in the UK. Ordinary least squares (OLS) regression was used to estimate models of increasing complexity in order to predict individuals’ SF-6D utility scores from their responses to the LupusQoL questionnaire. Model performance was judged on predictive ability through the size and pattern of prediction errors generated. The performance of the selected model was externally validated on an independent data set containing 113 female SLE patients who had again completed both the LupusQoL and SF-36 questionnaires. Results Four of the eight LupusQoL domains (physical health, pain, emotional health, and fatigue) were selected as dependent variables in the final model. Overall model fit was good, with R2 0.7219, MAE 0.0557, and RMSE 0.0706 when applied to the estimation data set, and R2 0.7431, MAE 0.0528, and RMSE 0.0663 when applied to the validation sample. Conclusion This study provides a method by which health state utility values can be estimated from patient responses to the non-preference-based LupusQoL, generalisable beyond the data set upon which it was estimated. Despite concerns over the use of OLS to develop mapping algorithms, we find this method to be suitable in this case due to the normality of the SF-6D data

Quantum decoherence of phonons in Bose–Einstein condensates

We apply modern techniques from quantum optics and quantum information science to Bose–Einstein condensates(BECs)in order to study, for the first time, the quantum decoherence of phonons of isolated BECs. In the last few years, major advances in the manipulation and control of phonons have highlighted their potential as carriers of quantum information in quantum technologies, particularly in quantum processing and quantum communication. Although most of these studies have focused on trapped ion and crystalline systems, another promising system that has remained relatively unexplored is BECs. The potential benefits in using this system have been emphasized recently with proposals of relativistic quantum devices that exploit quantum states of phonons in BECs to achieve, in principle, superior performance over standard non-relativistic devices. Quantum decoherence is often the limiting factor in the practical realization of quantum technologies, but here we show that quantum decoherence of phonons is not expected to heavily constrain the performance of these proposed relativistic quantum devices

Vision-Based Detection of Uncooperative Targets and Components on Small Satellites

Space debris and inactive satellites pose a threat to the safety and integrity of operational spacecraft and motivate the need for space situational awareness techniques. These uncooperative targets create a challenging tracking and detection problem due to a lack of prior knowledge of their features, trajectories, or even existence. Recent advancements in computer vision models can be used to improve upon existing methods for tracking such uncooperative targets to make them more robust and reliable to the wide-ranging nature of the target. This paper introduces an autonomous detection model designed to identify and monitor these objects using learning and computer vision. The autonomous detection method aims to identify and accurately track the uncooperative targets in varied circumstances, including different camera spectral sensitivities, lighting, and backgrounds. Our method adapts to the relative distance between the observing spacecraft and the target, and different detection strategies are adjusted based on distance. At larger distances, we utilize You Only Look Once (YOLOv8), a multitask Convolutional Neural Network (CNN), for zero-shot and domain-specific single-shot real time detection of the target. At shorter distances, we use knowledge distillation to combine visual foundation models with a lightweight fast segmentation CNN (Fast-SCNN) to segment the spacecraft components with low storage requirements and fast inference times, and to enable weight updates from earth and possible onboard training. Lastly, we test our method on a custom dataset simulating the unique conditions encountered in space, as well as a publicly-available dataset

Genomic complexity of the variable region-containing chitin-binding proteins in amphioxus

<p>Abstract</p> <p>Background</p> <p>The variable region-containing chitin-binding proteins (VCBPs) are found in protochordates and consist of two tandem immunoglobulin variable (V)-type domains and a chitin-binding domain. We previously have shown that these polymorphic genes, which primarily are expressed in the gut, exhibit characteristics of immune genes. In this report, we describe VCBP genomic organization and characterize adjacent and intervening genetic features which may influence both their polymorphism and complex transcriptional repertoire.</p> <p>Results</p> <p>VCBP genes 1, 2, 4, and 5 are encoded in a single contiguous gene-rich chromosomal region and VCBP3 is encoded in a separate locus. The VCBPs exhibit extensive haplotype variation, including copy number variation (CNV), indel polymorphism and a markedly elevated variation in repeat type and density. In at least one haplotype, inverted repeats occur more frequently than elsewhere in the genome. Multi-animal cDNA screening, as well as transcriptional profilingusing a novel transfection system, suggests that haplotype-specific transcriptional variants may contribute to VCBP genetic diversity.</p> <p>Conclusion</p> <p>The availability of the <it>Branchiostoma floridae </it>genome (Joint Genome Institute, Brafl1), along with BAC and PAC screening and sequencing described here, reveal that the relatively limited number of VCBP genes present in the amphioxus genome exhibit exceptionally high haplotype variation. These VCBP haplotypes contribute a diverse pool of allelic variants, which includes gene copy number variation, pseudogenes, and other polymorphisms, while contributing secondary effects on gene transcription as well.</p