Partial Covering Arrays: Algorithms and Asymptotics

A covering array $\mathsf{CA}(N;t,k,v)$ is an $N\times k$ array with entries in $\{1, 2, \ldots , v\}$, for which every $N\times t$ subarray contains each $t$-tuple of $\{1, 2, \ldots , v\}^t$ among its rows. Covering arrays find application in interaction testing, including software and hardware testing, advanced materials development, and biological systems. A central question is to determine or bound $\mathsf{CAN}(t,k,v)$, the minimum number $N$ of rows of a $\mathsf{CA}(N;t,k,v)$. The well known bound $\mathsf{CAN}(t,k,v)=O((t-1)v^t\log k)$ is not too far from being asymptotically optimal. Sensible relaxations of the covering requirement arise when (1) the set $\{1, 2, \ldots , v\}^t$ need only be contained among the rows of at least $(1-\epsilon)\binom{k}{t}$ of the $N\times t$ subarrays and (2) the rows of every $N\times t$ subarray need only contain a (large) subset of $\{1, 2, \ldots , v\}^t$. In this paper, using probabilistic methods, significant improvements on the covering array upper bound are established for both relaxations, and for the conjunction of the two. In each case, a randomized algorithm constructs such arrays in expected polynomial time

The age of anxiety? It depends where you look: changes in STAI trait anxiety, 1970–2010

Purpose Population-level surveys suggest that anxiety has been increasing in several nations, including the USA and UK. We sought to verify the apparent anxiety increases by looking for systematic changes in mean anxiety questionnaire scores from research publications. Methods We analyzed all available mean State–Trait Anxiety Inventory scores published between 1970 and 2010. We collected 1703 samples, representing more than 205,000 participants from 57 nations. Results Results showed a significant anxiety increase worldwide, but the pattern was less clear in many individual nations. Our analyses suggest that any increase in anxiety in the USA and Canada may be limited to students, anxiety has decreased in the UK, and has remained stable in Australia. Conclusions Although anxiety may have increased worldwide, it might not be increasing as dramatically as previously thought, except in specific populations, such as North American students. Our results seem to contradict survey results from the USA and UK in particular. We do not claim that our results are more reliable than those of large population surveys. However, we do suggest that mental health surveys and other governmental sources of disorder prevalence data may be partially biased by changing attitudes toward mental health: if respondents are more aware and less ashamed of their anxiety, they are more likely to report it to survey takers. Analyses such as ours provide a useful means of double-checking apparent trends in large population surveys

Detection of YAP1 and AR-V7 mRNA for prostate cancer prognosis using an ISFET lab-on-chip platform

Prostate cancer (PCa) is the second most common cause of male cancer-related death worldwide. The gold standard of treatment for advanced PCa is androgen deprivation therapy (ADT). However, eventual failure of ADT is common and leads to lethal metastatic castration-resistant PCa. As such, the detection of relevant biomarkers in the blood for drug resistance in metastatic castration-resistant PCa patients could lead to personalized treatment options. mRNA detection is often limited by the low specificity of qPCR assays which are restricted to specialized laboratories. Here, we present a novel reverse-transcription loop-mediated isothermal amplification assay and have demonstrated its capability for sensitive detection of AR-V7 and YAP1 RNA (3 × 101 RNA copies per reaction). This work presents a foundation for the detection of circulating mRNA in PCa on a non-invasive lab-on-chip device for use at the point-of-care. This technique was implemented onto a lab-on-chip platform integrating an array of chemical sensors (ion-sensitive field-effect transistors) for real-time detection of RNA. Detection of RNA presence was achieved through the translation of chemical signals into electrical readouts. Validation of this technique was conducted with rapid detection (<15 min) of extracted RNA from prostate cancer cell lines 22Rv1s and DU145s

Cardiotoxicity and cardiovascular disease risk assessment for patients receiving breast cancer treatment

Background: Cardiotoxicity from anticancer therapy affects heart function and structure. Cardiotoxicity can also lead to accelerated development of chronic diseases, especially in the presence of risk factors. Methods: This study aimed to develop and pilot a combined cardiovascular disease and cardiotoxicity risk assessment questionnaire to quantify the potential extent of risk factors in breast cancer patients prior to treatment. The questionnaire underwent content and face validity evaluation by an expert panel followed by pilot testing in a sample of breast cancer patients (n = 36). Questionnaires were self-administered while attending chemotherapy clinic, in the presence of a research assistant. Results: Mean age of participants was 54.8 years (range 36–72 years). Participants reported CVD risk factors including diabetes 2.8%, hypertension 19.8%, hypercholesterolaemia 11% and sleep apnoea 5%. Lifestyle risk factors, included not eating the recommended serves of vegetables (100%) or fruit (78%) per day; smoking (13%) and regularly consuming alcohol (75%). Twenty five percent reported being physically inactive, 61%, overweight or obese, 24%, little or no social support and 30% recorded high to very high psychological distress. Participants were highly (75%) reluctant to undertake lifestyle changes; i.e. changing alcohol consumption; dietary habits; good emotional/mental health strategies; improving physical activity; quitting smoking; learning about heart-health and weight loss. Conclusion: This study is an important step towards prevention and management of treatment-associated cardiotoxicity after breast cancer diagnosis. We recommend that our questionnaire is providing important data that should be included in cancer registries so that researchers can establish the relationship between CVD risk profile and cardiotoxicity outcomes and that this study revealed important teaching opportunities that could be used to examine the impact on health literacy and help patients better understand the consequences of cancer treatment

Fixed-Parameter Tractable Distances to Sparse Graph Classes

We show that for various classes $\mathcal{C}$ of sparse graphs, and several measures of distance to such classes (such as edit distance and elimination distance), the problem of determining the distance of a given graph $\small{G}$ to $\mathcal{C}$ is fixed-parameter tractable. The results are based on two general techniques. The first of these, building on recent work of Grohe et al. establishes that any class of graphs that is slicewise nowhere dense and slicewise first-order definable is FPT. The second shows that determining the elimination distance of a graph $\small{G}$ to a minor-closed class $\mathcal{C}$ is FPT. We demonstrate that several prior results (of Golovach, Moser and Thilikos and Mathieson) on the fixed-parameter tractability of distance measures are special cases of our first method

Tracking the evolutionary history of Cortinarius species in section Calochroi, with transoceanic disjunct distributions

<p>Abstract</p> <p>Background</p> <p><it>Cortinarius </it>species in section <it>Calochroi </it>display local, clinal and circumboreal patterns of distribution across the Northern Hemisphere where these ectomycorrhizal fungi occur with host trees throughout their geographical range within a continent, or have disjunct intercontinental distributions, the origins of which are not understood. We inferred evolutionary histories of four species, 1) <it>C</it>. <it>arcuatorum</it>, 2) <it>C. aureofulvus</it>, 3) <it>C</it>. <it>elegantior </it>and 4) <it>C. napus</it>, from populations distributed throughout the Old World, and portions of the New World (Central- and North America) based on genetic variation of 154 haplotype internal transcribed spacer (ITS) sequences from 83 population samples. By describing the population structure of these species across their geographical distribution, we attempt to identify their historical migration and patterns of diversification.</p> <p>Results</p> <p>Models of population structure from nested clade, demographic and coalescent-based analyses revealed genetically differentiated and geographically structured haplotypes in <it>C</it>. <it>arcuatorum </it>and <it>C</it>. <it>elegantior</it>, while <it>C</it>. <it>aureofulvus </it>showed considerably less population structure and <it>C. napus </it>lacked sufficient genetic differentiation to resolve any population structure. Disjunct populations within <it>C</it>. <it>arcuatorum, C. aureofulvus </it>and <it>C</it>. <it>elegantior </it>show little or no morphological differentiation, whereas in <it>C. napus </it>there is a high level of homoplasy and phenotypic plasticity for veil and lamellae colour. The ITS sequences of the type specimens of <it>C. albobrunnoides </it>and <it>C. albobrunnoides </it>var. <it>violaceovelatus </it>were identical to one another and are treated as one species with a wider range of geographic distribution under <it>C. napus</it>.</p> <p>Conclusions</p> <p>Our results indicate that each of the <it>Calochroi </it>species has undergone a relatively independent evolutionary history, hypothesised as follows: 1) a widely distributed ancestral population of <it>C</it>. <it>arcuatorum </it>diverged into distinctive sympatric populations in the New World; 2) two divergent lineages in <it>C</it>. <it>elegantior </it>gave rise to the New World and Old World haplotypes, respectively; and 3) the low levels of genetic divergence within <it>C</it>. <it>aureofulvus </it>and <it>C</it>. <it>napus </it>may be the result of more recent demographic population expansions. The scenario of migration via the Bering Land Bridge provides the most probable explanation for contemporaneous disjunct geographic distributions of these species, but it does not offer an explanation for the low degree of genetic divergence between populations of <it>C. aureofulvus </it>and <it>C. napus</it>. Our findings are mostly consistent with the designation of New World allopatric populations as separate species from the European counterpart species <it>C. arcuatorum </it>and <it>C. elegantior</it>. We propose the synonymy of <it>C. albobrunnoides</it>, <it>C. albobrunnoides </it>var. <it>violaceovelatus </it>and <it>C. subpurpureophyllus </it>var. <it>sulphureovelatus </it>with <it>C. napus</it>. The results also reinforce previous observations that linked <it>C. arcuatorum </it>and <it>C. aureofulvus </it>displaying distributions in parts of North America and Europe. Interpretations of the population structure of these fungi suggest that host tree history has heavily influenced their modern distributions; however, the complex issues related to co-migration of these fungi with their tree hosts remain unclear at this time.</p

The collagen receptor discoidin domain receptor 1b enhances integrin β1-mediated cell migration by interacting with talin and promoting Rac1 activation.

Integrins and discoidin domain receptors (DDRs) 1 and 2 promote cell adhesion and migration on both fibrillar and non fibrillar collagens. Collagen I contains DDR and integrin selective binding motifs; however, the relative contribution of these two receptors in regulating cell migration is unclear. DDR1 has five isoforms (DDR1a-e), with most cells expressing the DDR1a and DDR1b isoforms. We show that human embryonic kidney 293 cells expressing DDR1b migrate more than DDR1a expressing cells on DDR selective substrata as well as on collagen I in vitro. In addition, DDR1b expressing cells show increased lung colonization after tail vein injection in nude mice. DDR1a and DDR1b differ from each other by an extra 37 amino acids in the DDR1b cytoplasmic domain. Interestingly, these 37 amino acids contain an NPxY motif which is a central control module within the cytoplasmic domain of β integrins and acts by binding scaffold proteins, including talin. Using purified recombinant DDR1 cytoplasmic tail proteins, we show that DDR1b directly binds talin with higher affinity than DDR1a. In cells, DDR1b, but not DDR1a, colocalizes with talin and integrin β1 to focal adhesions and enhances integrin β1-mediated cell migration. Moreover, we show that DDR1b promotes cell migration by enhancing Rac1 activation. Mechanistically DDR1b interacts with the GTPase-activating protein (GAP) Breakpoint cluster region protein (BCR) thus reducing its GAP activity and enhancing Rac activation. Our study identifies DDR1b as a major driver of cell migration and talin and BCR as key players in the interplay between integrins and DDR1b in regulating cell migration

Multi-Scale Sampling to Evaluate Assemblage Dynamics in an Oceanic Marine Reserve

To resolve the capacity of Marine Protected Areas (MPA) to enhance fish productivity it is first necessary to understand how environmental conditions affect the distribution and abundance of fishes independent of potential reserve effects. Baseline fish production was examined from 2002–2004 through ichthyoplankton sampling in a large (10,878 km2) Southern Californian oceanic marine reserve, the Cowcod Conservation Area (CCA) that was established in 2001, and the Southern California Bight as a whole (238,000 km2 CalCOFI sampling domain). The CCA assemblage changed through time as the importance of oceanic-pelagic species decreased between 2002 (La Niña) and 2003 (El Niño) and then increased in 2004 (El Niño), while oceanic species and rockfishes displayed the opposite pattern. By contrast, the CalCOFI assemblage was relatively stable through time. Depth, temperature, and zooplankton explained more of the variability in assemblage structure at the CalCOFI scale than they did at the CCA scale. CalCOFI sampling revealed that oceanic species impinged upon the CCA between 2002 and 2003 in association with warmer offshore waters, thus explaining the increased influence of these species in the CCA during the El Nino years. Multi-scale, spatially explicit sampling and analysis was necessary to interpret assemblage dynamics in the CCA and likely will be needed to evaluate other focal oceanic marine reserves throughout the world

Time-dependent failure in load-bearing polymers: a potential hazard in structural applications of polylactides

With their excellent biocompatibility and relatively high mechanical strength, polylactides are attractive candidates for application in load-bearing, resorbable implants. Pre-clinical studies provided a proof of principle for polylactide cages as temporary constructs to facilitate spinal fusion, and several cages already made it to the market. However, also failures have been reported: clinical studies reported considerable amounts of subsidence with lumbar spinal fusion cages, and in an in vivo goat study, polylactide spinal cages failed after only three months of implantation, although mechanical testing had predicted sufficient strength for at least eight months. The failures appear to be related to the long-term performance of polylactides under static loading conditions, a phenomenon which is common to all glassy polymers and finds its origin in stress-activated molecular mobility leading to plastic flow. This paper reviews the mechanical properties and deformation kinetics of amorphous polylactides. Compression tests were performed with various strain rates, and static stress experiments were done to determine time-to failure. Pure PLLA appeared to have a higher yield strength than its co-polymers with d-lactide, but the kinetic behaviour of the polymers was the same: an excellent short-term strength at higher loading rates, but lifetime under static stress is rather poor. As spinal implants need to maintain mechanical integrity for a period of at least six months, this has serious implications for the clinical application of amorphous polylactides in load bearing situations. It is recommended that standards for mechanical testing of implants made of polymers be revised in order to consider this typical time-dependent behaviour

Symptoms of Anxiety and Cardiac Hospitalizations at 12 Months in Patients with Heart Failure

OBJECTIVE: Heart failure (HF) is a leading cause of hospitalization. Clinical and socio-demographic factors have been associated with cardiac admissions, but little is known about the role of anxiety. We examined whether symptoms of anxiety were associated with cardiac hospitalizations at 12 months in HF patients. METHODS: HF outpatients (N=237) completed the Hospital Anxiety and Depression Scale (HADS) at baseline (i.e., inclusion into the study). A cutoff ≥8 was used to indicate probable clinical levels of anxiety and depression. At 12 months, a medical chart abstraction was performed to obtain information on cardiac hospitalizations. RESULTS: The prevalence of symptoms of anxiety was 24.9 % (59/237), and 27.0 % (64/237) of patients were admitted for cardiac reasons at least once during the 12-month follow-up period. Symptoms of anxiety were neither significantly associated with cardiac hospitalizations in univariable logistic analysis [OR=1.13, 95% CI (0.59–2.17), p=0.72] nor in multivariable analysi