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Despite the popularity of feature importance (FI) measures in interpretable machine learning, the statistical adequacy of these methods is rarely discussed. From a statistical perspective, a major distinction is between analysing a variable’s importance before and after adjusting for covariates—i.e., between marginal and conditional measures. Our work draws attention to this rarely acknowledged, yet crucial distinction and showcases its implications. We find that few methods are available for testing conditional FI and practitioners have hitherto been severely restricted in method application due to mismatched data requirements. Most real-world data exhibits complex feature dependencies and incorporates both continuous and categorical features (i.e., mixed data). Both properties are oftentimes neglected by conditional FI measures. To fill this gap, we propose to combine the conditional predictive impact (CPI) framework with sequential knockoff sampling. The CPI enables conditional FI measurement that controls for any feature dependencies by sampling valid knockoffs—hence, generating synthetic data with similar statistical properties—for the data to be analysed. Sequential knockoffs were deliberately designed to handle mixed data and thus allow us to extend the CPI approach to such datasets. We demonstrate through numerous simulations and a real-world example that our proposed workflow controls type I error, achieves high power, and is in-line with results given by other conditional FI measures, whereas marginal FI metrics can result in misleading interpretations. Our findings highlight the necessity of developing statistically adequate, specialized methods for mixed data.

Unsupervised learning algorithms are widely used for many important statistical tasks with numerous applications in science and industry. Yet despite their prevalence, they have attracted remarkably little philosophical scrutiny to date. This stands in stark contrast to supervised and reinforcement learning algorithms, which have been widely studied and critically evaluated, often with an emphasis on ethical concerns. In this article, I analyze three canonical unsupervised learning problems: clustering, abstraction, and generative modeling. I argue that these methods raise unique epistemological and ontological questions, providing data-driven tools for discovering natural kinds and distinguishing essence from contingency. This analysis goes some way toward filling the lacuna in contemporary philosophical discourse on unsupervised learning, as well as bringing conceptual unity to a heterogeneous field more often described by what it is not (i.e., supervised or reinforcement learning) than by what it is. I submit that unsupervised learning is not just a legitimate subject of philosophical inquiry but perhaps the most fundamental branch of all AI. However, an uncritical overreliance on unsupervised methods poses major epistemic and ethical risks. I conclude by advocating for a pragmatic, error-statistical approach that embraces the opportunities and mitigates the challenges posed by this powerful class of algorithms.

Plantago ovatais cultivated for production of its seed husk (psyllium). When wet, the husk transforms into a mucilage with properties suitable for pharmaceutical industries, utilised in supplements for controlling blood cholesterol levels, and food industries for making gluten-free products. There has been limited success in improving husk quantity and quality through breeding approaches, partly due to the lack of a reference genome. Here we constructed the first chromosome-scale reference assembly ofP. ovatausing a combination of 5.98 million PacBio and 636.5 million Hi-C reads. We also used corrected PacBio reads to estimate genome size and transcripts to generate gene models. The final assembly covers ~ 500 Mb with 99.3% gene set completeness. A total of 97% of the sequences are anchored to four chromosomes with an N50 of ~ 128.87 Mb. TheP. ovatagenome contains 61.90% repeats, where 40.04% are long terminal repeats. We identified 41,820 protein-coding genes, 411 non-coding RNAs, 108 ribosomal RNAs, and 1295 transfer RNAs. This genome will provide a resource for plant breeding programs to, for example, reduce agronomic constraints such as seed shattering, increase psyllium yield and quality, and overcome crop disease susceptibility.

Background Patient navigation is an increasingly widespread intervention to address the persistent, severe, and disproportionate breast cancer (BC) burden that African Americans (AA) face. Navigation may have more widespread effects than previously estimated due to patient-driven diffusion of BC information. Methods This pilot study examined the network effects of a randomized controlled trial via recruitment of navigated and non-navigated AA BC patients as well as their network members. We estimated study arm differences in patient BC promotion (i.e., number of individuals to whom BC patients promote BC screening) and network BC screening (i.e., % BC screening among network members). Results Among our sample of 100 AA BC patients, navigated patients promoted BC screening to more individuals than non-navigated patients. BC patients were more likely to promote BC screening to children and individuals with whom they communicated more frequently. Some models further suggested more network BC screening among "navigated" network members relative to "non-navigated" network members. Conclusions Navigated AA patients promoted BC screening more widely throughout their networks than non-navigated AA BC patients. There were also suggestive findings regarding increased BC screening among their network members. Our pilot study highlights the potential for social network analysis to improve the precision of intervention effect estimates and to inform future innovations (e.g., integrating navigation and network-based interventions) with multilevel effects on cancer health disparities.

We compute the free energy and surface tension function for the five-vertex model, a model of non-intersecting monotone lattice paths on the grid in which each corner gets a positive weight. We give a variational principle for limit shapes in this setting, and show that the resulting Euler-Lagrange equation can be integrated, giving explicit limit shapes parameterized by analytic functions., 37 pages, 21 figures

Multilevel barriers can arise after a cancer diagnosis, especially in underserved racial/ethnic minority patient populations, raising the need for diverse and contextually adapted interventions. However, limited data exists on Arab American (ArA) cancer patients’ needs, partly due to their racial/ethnic misclassification as Whites. This study leveraged the perspectives of cancer survivors and community stakeholders (i.e., healthcare and community leaders) to identify ArA cancer patients’ needs, as well as their preferred intervention strategies to address them. Using a hybrid inductive-deductive content analysis approach, we analyzed qualitative data from interviews with 18 ArA community stakeholders recruited through community partners in Chicago. Participants associated cancer stigma to ArA patients’ concealment of their diagnosis and aversion to cancer support groups. Economic and language barriers to treatment were emphasized. A lack of resources for ArA cancer patients was also noted and was partly attributed to their misclassification as White. In response to these needs, participants suggested peer mentorship programs to overcome privacy concerns, hospital-based patient navigation to address language and economic barriers in healthcare, diversification of the healthcare workforce to overcome language barriers, and community coalitions to recognize ArA as an ethnic group and increase cancer support resources. Such advocacy will be essential to accurately characterize patients’ cancer burden and obtain funding to support community programs and resources. Our findings suggest that multilevel interventions at the patient, healthcare, and community levels are needed to address ArA cancer patients’ needs.

PURPOSE: Social support improves several quality of life (QOL) domains among African American breast cancer survivors. Further, how different dimensions of social support are associated with QOL among African American breast cancer survivors may differ from other populations. This study explores this hypothesis by examining associations of positive social support (supportive interactions that promote affection) and negative social support (non-supportive interactions or interactions wherein the provider of support may not have the best intended actions) with QOL among Chicago-based African American breast cancer survivors. METHODS: Study participants were eligible if they: 1) identified as being an African American female, 2) were at least 18 years of age or older, and 3) were diagnosed with breast cancer during or after navigation was implemented at the study hospital. Participants completed validated questionnaires via telephone or in-person interviews. RESULTS: Among our sample of 100 participants, positive support was associated with greater mental well-being in non-imputed (Std β=1.60, CI: 0.51, 2.69, p= 0.004) and imputed models (Std β= 1.67, CI: 0.68, 2.73, p=0.001). There was also a weaker inverse association with negative support and mental well-being when using non-imputed data (Std β=−0.82, CI: −1.65, 0.02, p= 0.05). CONCLUSIONS: Our findings suggest that positive support, in particular, is highly influential for improving mental well-being among African American breast cancer survivors. Simultaneously, negative support appears to be an independent, albeit weaker, determinant of mental well-being.

Air pollutant concentration of Trivandrum, the capital of Kerala, exceeded the limits of National Ambient Air Quality (NAAQ) standards, according to a study conducted in 2015 by NATPAC. These polluted corridors harbour vegetation on roadsides and traffic islands, planted solely for aesthetic appeal. Analysis of air pollution tolerance levels of existing plants can act as a scientific basis for efficient planning of the urban landscape. Sixty-seven species, including flowering, fruit-bearing, ornamental, shade-providing and timber-yielding species, were screened for their relative resistance to air pollution. Based on leaf pH, relative water content, chlorophyll and ascorbic acid levels, the Air Pollution Tolerance Indices (APTI) of each species were formulated and they were grouped into the following: tolerant, moderately tolerant, intermediate and sensitive groups. Agave americana (18.40), Cassia roxburghii (17.63), Anacardium occidentale (11.97), Cassia fistula (11.60), Mangifera indica (11.59) and Saraca asoca (10.88) may be considered for planting near green spaces like roundabouts and near pollution prone industrial areas, as they belong to tolerant category. Comparison of APTI during summer and monsoon also revealed the stability of Agave americana, Saraca asoca, Ficus benghalensis, Peltophorum pterocarpum, Ficus elastica, Ixora finlaysoniana, Mangifera indica, Canna indica and Delonix regia in maintaining pollution tolerance even during water disparity. Agave americana, Anacardium occidentale, Ficus elastica, Mangifera indica, Syzygium cumini, Ficus benghalensis, Nerium oleander and Ficus benjamina were found to be suited for mass planting, as was evident from their Anticipated Performance Indices (API).

This study level process design represents an economically viable method for extracting thorium dioxide and other rare earth elements from monazite ore. This paper incorporates results from the 2019 capstone project from the honors Design Internship in Green Engineering in Chemical and Biomolecular Engineering. In this activity, senior students in Chemical Engineering at the University of Tennessee (UT) focused on the development and study of a process for the recovery of thorium dioxide and P2O5 from monazite. While not mandated, the process offers rare earth oxides as attractive byproducts. The project focused on recovery of byproducts rather than the creation or addition to waste streams. Additionally, (1) the process economics relied heavily on recovery of rare earth byproducts, (2) thorium handling portions of the process could be effectively segregated from rare earth and phosphate handling portions of the process, and (3) thorium and uranium content of waste streams should be carefully managed and eliminated where possible.

In an effort to explore new knowledge and to develop meaningful collaborations for improving child health, the First Pan African Workshop on Newborn Screening was convened in June 2019 in Rabat, Morocco. Participants included an informal network of newborn screening stakeholders from across Africa and global experts in newborn screening and sickle cell disease. Over 150 attendees, representing 20 countries, were present including 11 African countries. The agenda focused on newborn screening rationale, techniques, system development, implementation barriers, ongoing research, and collaborations both globally and across Africa. We provide an overview of the workshop and a description of the newborn screening activities in the 11 African countries represented at the workshop, with a focus on sickle cell disease.

Objective Soybean is an important plant used for food, feed and many industrial purposes. Interest in soybean breeding is growing in Central Europe, including Poland. A very large number of soybean accessions are stored in gene banks, but less than 1% of them have been used for breeding. Here, we present genotypic data as well as phenotypic data on plant and seed performance, including seed chlorophyll fluorescence traits, and on yield components within a collection of soybean accessions that are conserved in the Polish Gene Bank at the Plant Breeding and Acclimatization Institute-National Research Institute. Results The materials used consisted of sub-collections: 79 Polish genotypes, including old traditional cultivars, 24 Canadian, 21 American, 21 Swedish and 31 from Central and Eastern European Countries, 9 from France and 6 from Japan. In total, 9602 high quality SNPs were derived from DArTseq, a method utilising GBS technology. GWAS, performed with the BLINK model, revealed that a total of 41 significant SNPs were mapped for days to flowering, flower colour, plant height, days to pod formation, 100 seed weight, pod colour, seeds and hilum colour and steady-state chlorophyll fluorescence under light (Ft_Lss). This is the first report about the diversity of traditional old Polish soybean cultivars.

The design of multimedia elements used in video for online courses can increase student perceptions of their instructor’s credibility and immediacy. Credibility is the learner’s perception of the subject matter expertise of the instructor, while immediacy is the learner’s perception of the instructor’s ability to communicate and reduce physiological distance. This experiment randomly assigned research participants (N = 211) into one of five independent treatment groups, each group viewed a different design based on the same subject matter, instructor video, audio narration, and presentation slides. These presentation designs included an instructor-only, slides-only, video-switching, dual-windows, and a superimposed-slides multimedia design variation. A series of 5 × 1 Analyses of variances and Tukey post hoc calculations were conducted to test for statistically significant differences between groups. The results suggest that a balance can be established between instructor credibility and immediacy by showing both the instructor and instructional content during online classes.

PURPOSE: We explored how the number of lifetime comorbidities and treatment-related cancer symptoms were associated with quality of life (QOL) in rural cancer survivors. METHODS: Survivors (n = 125) who were rural Illinois residents aged 18+ years old were recruited from January 2017-September 2018. We conducted 4 multivariable regressions with QOL domains as outcomes (social well-being, functional well-being, mental health-MHQOL, physical health - PHQOL); the number of physical and psychological comorbidities (e.g. arthritis, high blood pressure, stroke) and treatment-related cancer symptoms (e.g. worrying, feeling sad, lack of appetite, lack of energy) as predictors; and, cancer-related and demographic factors related to these variables as covariates. RESULTS: The number of comorbidities and treatment-related symptoms were inversely associated with functional well-being (B=−0.36, p

This phenomenological study explores the ethical challenges experienced by both supervisors and supervisees in transnational settings. Thirty-two participants from sixteen countries completed an open-ended, short-answer survey of their experiences with ethical issues in supervision. Emerging themes were identified and results were sent to participants for review and additional responses. Findings revealed that multiple relationships, mandated reporting, and the lack of cultural discussions within supervisory settings were the most frequently cited ethical concerns identified by participants. The researchers propose specific practices for translating ethics in international supervision contexts that avoids a one-size-fits-all mindset through fostering ethical contextualization and acculturation.

Waste phosphatic clay presents a difficult disposal problem and a significant loss of P2O5. Recent developments make this study on the use of phosphatic clay as a feed material for H3PO4 production worthwhile. (a) New data from Florida Industrial and Phosphate Research Institute (FIPR) suggest that the “clay” waste can be effectively treated by improved solid separation coupled with flotation to produce feed material for recovering additional phosphate. (b) The use of “OLI Flowsheet” provides capability to predict performance of aqueous-based processes for a range of possible operating conditions. Using the new FIPR data and “OLI Flowsheet” enabled the design of a new process that can potentially extend the usefulness of current P2O5 ore deposits. Predictions using OLI Flowsheet were able to identify process conditions that effectively overcome the difficulty of high Mg content of phosphatic clay. Estimated manufacturing cost in the current study lead to valuation of the P2O5 content of the phosphatic clay recovered/utilized at 60 to 70% of that of the phosphate rock feed material currently used. Phosphatic clay should be considered as a valuable material that is currently given zero value. The new FIPR data and “OLI Flowsheet” enables the design of a new process that can potentially extend the usefulness of current phosphate ore deposits by extending the fraction P2O5 of recovered.

Elite wheat pollinators are critical for successful hybrid breeding. We identified Rht-B1 and Ppd-D1 loci affecting multiple pollinator traits and therefore represent major targets for improving hybrid seed production. Hybrid breeding has a great potential to significantly boost wheat yields. Ideal male pollinators would be taller in stature, contain many spikelets well-spaced along the spike and exhibit high extrusion of large anthers. Most importantly, flowering time would match with that of the female parent. Available genetic resources for developing an elite wheat pollinator are limited, and the genetic basis for many of these traits is largely unknown. Here, we report on the genetic analysis of pollinator traits using biparental mapping populations. We identified two anther extrusion QTLs of medium effect, one on chromosome 1BL and the other on 4BS coinciding with the semi-dwarfing Rht-B1 locus. The effect of Rht-B1 alleles on anther extrusion is genotype dependent, while tall plant Rht-B1a allele is consistently associated with large anthers. Multiple QTLs were identified at the Ppd-D1 locus for anther length, spikelet number and spike length, with the photoperiod-sensitive Ppd-D1b allele associated with favourable pollinator traits in the populations studied. We also demonstrated that homeoloci, Rht-D1 and Ppd-B1, influence anther length among other traits. These results suggest that combinations of Rht-B1 and Ppd-D1 alleles control multiple pollinator traits and should be major targets of hybrid wheat breeding programs.

To address locally relevant cancer-related health issues, health departments frequently need data beyond that contained in standard census area-based statistics. We describe a geographic information system-based method for calculating age-standardized cancer incidence rates in non-census defined geographical areas using publically available data. Aggregated records of cancer cases diagnosed from 2009 through 2013 in each of Chicago’s 77 census-defined community areas were obtained from the Illinois State Cancer Registry. Areal interpolation through dasymetric mapping of census blocks was used to redistribute populations and case counts from community areas to Chicago’s 50 politically defined aldermanic wards, and ward-level age-standardized 5-year cumulative incidence rates were calculated. Potential errors in redistributing populations between geographies were limited to

In order for Alzheimer’s disease (AD) to manifest, cells must communicate “pathogenic material” such as proteins, signaling molecules, or genetic material to ensue disease propagation. Small extracellular vesicles are produced via the endocytic pathways and released by nearly all cell types, including neurons. Due to their intrinsic interrelationship with endocytic processes and autophagy, there has been increased interest in studying the role of these neuronally-derived extracellular vesicles (NDEVs) in the propagation of AD. Pathologic cargo associated with AD have been found in a number of studies, and NDEVs have been shown to induce pathogenesis in vivo and in vitro. Exogenous NDEVs are also shown to reduce plaque burden in AD models. Thus, the NDEV has the potential to become a useful biomarker, a pathologic potentiator, and a therapeutic opportunity. While the field of NDEV research in AD is still in its infancy, we review the current literature supporting these three claims. Electronic supplementary material The online version of this article (10.1186/s13024-019-0317-5) contains supplementary material, which is available to authorized users.

African American men (AA) carry unequal burdens of several conditions including cancer, diabetes, hypertension, and HIV. Engagement of diverse populations including AA men in research and health promotion practice is vital to examining the health disparities that continue to plague many racially and ethnically diverse communities. To date, there is little research on best practices that indicate locations, community areas and settings to engage AA men in research and health promotion. Traditionally, the AA church has been a key area to engage AA men and women. However, changing tides in attendance of AA parishioners require additional information to identify areas where AAs, particularly, AA men congregate. The AA barbershop has been identified as a place of social cohesion, cultural immersion and solidarity for AA men but specific sub-populations of AA men may be underrepresented. To further investigate additional locales where AA men congregate, this study engaged AA barbers and clients in several urban community barbershops in Chicago, Illinois. 127 AA men over age 18y/o receiving grooming services in 25 Chicago area barbershops across 14 predominantly AA communities were consented and recruited for a quantitative survey study. The self-administered surveys were completed in ~15 min and $10 compensation was provided to men. Descriptive statistics were reported for demographic variables and for frequency of responses for locations to find AA men of specific age ranges for health promotion and screening activities. Outside of the traditionally used churches or barbershops, the top recommended recruitment sites by age were: 18–29y/o− city park or a recreational center; 30–39y/o− gym, bars or the street; 40–49y/o− various stores, especially home improvement stores, and the mall; and 50y/o+- fast food restaurants in the mornings, such as McDonalds, and individual’s homes. The study participants also reported that locations where AA men congregate vary by age. Findings from this study illustrate that AA barbers and barbershops remain a key stakeholder in health promotion among AA men. The findings also demonstrate the need for additional research to examine best practices for identifying locations where diverse groups of AA men that vary by age and sexual orientation may congregate in order to support increased health promotion among AA men.

Ethylene-vinyl acetate (EVA) is the most commonly used photovoltaic (PV) encapsulant material. As such, it is exposed to UV, thermal cycles, temperature gradients between the glass side and the silicon wafer side, and moisture ingress. The combined effect of all these may lead to different physical and chemical changes of EVA including polymer chain alignment, crystallinity, and crosslinking density, as well as the mechanical stresses resulting from coefficient of thermal expansion (CTE) and aging, thus, reducing the adhesion of EVA and eventually lead to failure of the encapsulation. Measuring the effects of UV exposure on EVA can help in understanding the failure mechanism of PV modules. In this work, we suggest a novel and non-destructive way to measure EVA degradation after UV exposure by using Raman spectroscopy (RS). Samples were exposed to NIST SPHERE with UV irradiation, moisture, and elevated temperatures. The physical and chemical changes as well as the internal stresses were monitored by RS, and the intensities of the corresponding Raman peaks ratio were analyzed. The results have indicated that Raman scattering is a sensitive tool to study EVA encapsulant degradation.

Melting/freezing points of AlCl3 in saturated chloroaluminate ionic liquids [molar ratio 2:1 AlCl3:1-ethyl-3-methyl imidazolium chloride (EMIC)] are measured by differential scanning calorimetry (DSC). A critical range of temperature data (50–130 °C) for AlCl3 dissolution and precipitation from saturated chloroaluminate ionic liquids is obtained. This range of temperature data is of significance to control phase transition of AlCl3 in saturated chloroaluminate ionic liquids. By applying the chloroaluminate ionic liquids to electrolytes for energy storage usage, solid AlCl3 can be partially dissolved and precipitated out during the charging/discharging cycle of energy storage equipment. Therefore, the energy density of the electrolytes is expected to be greatly improved.

This study examined the incorporation of generative strategies for the guided discovery of physics principles in a simulation. Participants who either paraphrased or predicted and self-explained guided discovery assignments exhibited improved performance on an achievement test as compared to a control group. Calibration accuracy (the correspondence between judgments of performance and actual performance) was also improved for the two generative strategy groups. The thoroughness of generative content and quality of self-explanations significantly predicted test performance. In regards to cognitive load, participants who predicted and self-explained reported significantly higher levels of mental effort, decreased levels of confidence, and higher levels of frustration compared to those in other treatments. The improvement in learning by the two generative strategy groups is consistent with the generative model of learning describing the importance of knowledge construction.

National and international public–private partnerships, consortia, and government initiatives are underway to collect and share genomic, personal, and healthcare data on a massive scale. Ideally, these efforts will contribute to the creation of a medical information commons (MIC), a comprehensive data resource that is widely available for both research and clinical uses. Stakeholder participation is essential in clarifying goals, deepening understanding of areas of complexity, and addressing long-standing policy concerns such as privacy and security and data ownership. This article describes eight core principles proposed by a diverse group of expert stakeholders to guide the formation of a successful, sustainable MIC. These principles promote formation of an ethically sound, inclusive, participant-centric MIC and provide a framework for advancing the policy response to data-sharing opportunities and challenges.

Assessments of watershed-based restoration efforts are rare but are essential for the science of stream restoration to advance. We conducted a watershed scale assessment of Abram Creek before and after implementation of a watershed-based plan designed to maximize ecological recovery from acid mine drainage (AMD) impairment. We surveyed water chemistry, physical habitat, benthic macroinvertebrates, and fish community structure in three stream types: AMD-impacted (14 streams), AMD-treated (13 streams), and unimpaired reference (4 streams). We used in-stream measurements to quantify ecological loss from AMD, the amount of ecological recovery expected through remediation, and the observed degree of post-treatment recovery. Sites impaired by AMD improved in water quality with AMD treatment. Dissolved metals and acidity declined significantly in treated streams, but sulfate and specific conductance did not. Likewise, sites impaired by AMD improved in bio-condition scores with AMD treatment. EPT genera increased significantly but were lower compared to unimpaired streams. We found fish at nine treated sites that had none before treatment. Community-level analyses indicated improved but altered assemblages with AMD treatment. Analysis of pre-treatment conditions indicated that only 30% of the historic fishery remained. Remediation was expected to recover 66% of the historic fishery value, and assessment of post-treatment conditions indicates that 52% of the historic fishery has been recovered after 3 years. Developing expected endpoints for restoration outcomes provides a tool to objectively evaluate successes and can guide adaptive management strategies.

We show that crossing probabilities in 2D critical site percolation on the triangular lattice in a piecewise analytic Jordan domain converge with power law rate in the mesh size to their limit given by the Cardy–Smirnov formula. We use this result to obtain new upper and lower bounds of \({e^{O(\sqrt{{\rm log}\,{\rm log} R})}\, R^{-1/3}}\) for the probability that the cluster at the origin in the half-plane has diameter R, improving the previously known estimate of R−1/3+o(1).

The majority of patients experience a significant improvement in quality of life and function after total hip replacement (THR). It has recently been shown that age and good pre-operative function are the best predictors of postoperative function. When patients fail to achieve a satisfactory outcome, a cause is often identified. Where there is no identifiable cause, advice, follow-up and management is not clear. The aim of this study was to determine the long-term outcome of patients who had early poor function, but no identifiable cause.From a regional database, we identified 1,564 patients who underwent unilateral THR between 1998 and 2004 and who were without complication or subsequent bilateral procedure at six months. These patients were divided into two groups according to their Harris hip score (HHS) at this stage: group A consisted of 270 patients with a 'poor' result (HHS less than 70). Group B consisted of 1,294 patients with a 'good' or 'excellent' result (HHS 70 or above). The patients were reviewed at five years. One hundred and ten patients from group A and 980 from group B completed five-year follow-up without further identifiable complication.Those with poor or fair function at six months were at an increased risk of developing an identified complication by five years including dislocation (OR 5.7, 95% CI 1.8-18.2), deep infection (OR 9.8, 95%CI 2.9-37.7) and death (OR 1.6, 95% CI 1.1-2.3). There was a greater rate of revision in group A versus group B (OR 5.7, 95% CI 2.9-11). The overall function measured by the Harris hip score significantly improved in group A, but never reached that of those with good or excellent function at six months (HHS 76.2 versus 90.3, P 0.001).Patients with poor function at six months, but no obvious cause, are at higher risk of developing complications by five years. This group may benefit from more regular arthroplasty review and intervention.

Susceptibility to deadly diarrheal diseases is partly due to widespread pediatric vitamin A deficiency. To increase vitamin A coverage in malnourished children, we propose to engineer a probiotic bacterium that will produce β-carotene in the intestine, which will be metabolized to vitamin A. Such a therapy has the potential to broadly stimulate mucosal immunity and simultaneously reduce the incidence and duration of diarrheal disease. To that end, a β-carotene-producing variant of the probiotic Escherichia coli strain Nissle 1917 (EcN-BETA) was generated. Notably, the strain produces β-carotene under anaerobic conditions, reflective of the gut environment. EcN-BETA also retains β-carotene production capability after lyophilization, suggesting that it may be amenable to dry formulation. Moreover, EcN-BETA activates murine dendritic cells in vitro, suggesting that the presence of β-carotene may not diminish the immunostimulatory capacity of EcN. Finally, we present a framework through which further improvements may enable approaches such as the one described in this report to yield innovative life-saving therapies for the developing world.

Background To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG) of the Clinical Genome Resource (ClinGen), in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD). MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice. Methods We developed MVLD through a consensus approach by i) reviewing clinical actionability interpretations from institutions participating in the WG, ii) conducting extensive literature search of clinical somatic interpretation schemas, and iii) survey of cancer variant web portals. A forthcoming guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP), can be incorporated into MVLD. Results Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data. Conclusions We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of somatic variants to ClinVar, all of which will enhance translation to clinical oncology practice. Electronic supplementary material The online version of this article (doi:10.1186/s13073-016-0367-z) contains supplementary material, which is available to authorized users.

With the long-term goal of developing a gene-based treatment for osteoarthritis (OA), we performed studies to evaluate the equine joint as a model for adeno-associated virus (AAV)-mediated gene transfer to large, weight-bearing human joints. A self-complementary AAV2 vector containing the coding regions for human interleukin-1-receptor antagonist (hIL-1Ra) or green fluorescent protein was packaged in AAV capsid serotypes 1, 2, 5, 8 and 9. Following infection of human and equine synovial fibroblasts in culture, we found that both were only receptive to transduction with AAV1, 2 and 5. For these serotypes, however, transgene expression from the equine cells was consistently at least 10-fold higher. Analyses of AAV surface receptor molecules and intracellular trafficking of vector genomes implicate enhanced viral uptake by the equine cells. Following delivery of 1 × 10(11) vector genomes of serotypes 2, 5 and 8 into the forelimb joints of the horse, all three enabled hIL-1Ra expression at biologically relevant levels and effectively transduced the same cell types, primarily synovial fibroblasts and, to a lesser degree, chondrocytes in articular cartilage. These results provide optimism that AAV vectors can be effectively adapted for gene delivery to large human joints affected by OA.

The service life and durability of nanocomposites containing fillers are affected by photocatalytic properties of these fillers, particularly narrow band gap metal oxides (NBMOs) such as titanium dioxide (TiO2). When irradiated with ultraviolet flux, NBMOs produce electrons and other species that are capable of causing rapid degradation of organic materials with which they are in contact. Electrons and holes (positively charged species) migrate to the surface and react with species to generate various free radicals. Measurement science tools for characterizing TiO2 photoreactivity using electron paramagnetic resonance (EPR) methods have been developed by the Engineering Laboratory (EL) at the National Institute of Standards and Technology (NIST) and a linkage between EPR measurements and current industrial methods has been established. A database of TiO2 photoreactivity values and other data measured via the EPR methods and industrial assays has been compiled and will be accessed through a searchable software database in the NIST Standard Reference Database program— http://www.nist.gov/srd/index.cfm . The database provides fundamental photoreactivity data that can be used for product selection and development purposes to enable more reliable assessments of end-performance.

Nanoparticle-filled polymeric coatings have attracted great interest in recent years because the incorporation of nanofillers can significantly enhance the mechanical, electrical, optical, thermal, and antimicrobial properties of coatings. Due to the small size of the fillers, the volume fraction of the nanoparticle/polymer interfacial area in nano-filled systems is drastically increased, and the interfacial region becomes important in the performance of the nano-filled system. However, techniques used for characterizing nanoparticle/polymer interfaces are limited, and thus, the mechanism by which interfacial properties affect the photostability and the long-term performance of nano-filled polymeric coatings is not well understood. In this study, the role of the nanoparticle/polymer interface on the ultraviolet (UV) stability of a nano-ZnO-filled polyurethane (PU) coating system was investigated. The effects of parameters influencing the particle/polymer interfacial properties, such as size, loading, surface modification of the nanoparticles, on photodegradation of ZnO/PU films were evaluated. The nature of the interfacial regions before and after UV exposures were characterized by atomic force microscopy (AFM)-based techniques. Results have shown that the interfacial properties strongly affect chemical, thermo-mechanical, and morphological properties of the UV-exposed ZnO/PU films. By combining tapping mode AFM and novel electric force microscopy (EFM), the particle/polymer interfacial regions have been successfully detected directly from the surface of the ZnO/PU films. Further, our results indicate that ZnO nanoparticles can function as a photocatalyst or a photostabilizer, depending on the UV exposure conditions. A hypothesis is proposed that the polymers in the vicinity of the ZnO/PU interface are preferentially degraded or protected, depending on whether ZnO nanoparticles act as a photocatalyst or a photostabilizer in the polymers. This study clearly demonstrates that the particle/polymer interface plays a critical role in the photostability of nano-filled polymeric coatings.

Metal oxide nanoparticles are small but easily form agglomerates in suspension, depending on the strength of particle–particle and particle–media interactions. To understand the agglomeration behavior of nanoparticles in media and relate to it to product performance testing, measurement methods are desired to characterize highly scattering metal oxide nanoparticle suspensions without dilution. In this article, we describe the advantages of using photocorrelation spectroscopy (PCS) in a backscattering detection configuration to carry out a realistic agglomerate size measurement in multiple scattering media found in most metal oxide nanoparticle suspensions. The dynamic behavior of nano-titanium dioxide (TiO2) particles in buffer solutions of different chemical composition and pH values was investigated as a sample system using PCS. The resulting autocorrelation functions (AFs) at different time intervals, particle concentrations, and pH values were measured at several detection angles. The AF exhibits a multi-mode relaxation time feature and the calculated hydrodynamic diameters strongly depended on media composition and detection angle. This result indicates that the size and dispersion of nano-TiO2 agglomerates are significantly affected by solution media. A measurement protocol for determining size and dispersion of metal oxide particles in media is proposed and related to a performance test found in industry.

The objective of this study was to investigate the effect of the photoreactivity of titanium dioxide (TiO2) pigments on the photodegradation of polymeric coatings used in exterior applications. Two polymer matrices, an amine-cured epoxy (EP) and an acrylic urethane (AU), containing three types of TiO2 pigments, classified by different levels of photoreactivity, were studied. Specimens were exposed on an ultraviolet (UV) weathering chamber, the Simulated Photodegradation by High Energy Radiant Exposure device at the National Institute of Standards and Technology. Two exposure conditions were used: ambient, dry condition [25°C and 0% relative humidity (RH)] and high temperature, wet condition (55°C and 75% RH), which is similar to more severe outdoor exposures. The physical and chemical degradations of the filled coatings were monitored at periodic intervals using a combination of laser scanning confocal microscopy (LSCM) and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). Progression of degradation on the coating surfaces was characterized by LSCM in terms of changes in surface roughness and morphology, pigment agglomerate size, and the occurrence of pits or holes in the coatings. The observed physical changes were correlated to the chemical changes measured by ATR-FTIR as a function of UV exposure time. Both EP and AU systems showed less degradation in terms of surface roughness and morphological changes under the dry conditions compared to the wet exposure conditions. It was observed that both the pigment type (and hence photoreactivity) and particle dispersion strongly affected the degradation of both EP and AU systems.

Objective This study was designed to test whether established post-total knee arthroplasty (TKA) bone loss at over 2 years post-surgery could be improved by 6 months of alendronate administration.

The purpose of this study was to investigate whether intraperitoneal instillation of Hartmann’s Solution reduces postoperative pain after diagnostic laparoscopy. The study design involved of a pilot, prospective randomised controlled trial. Location and participants included women attending day case unit in the gynaecology department of a district general hospital for elective laparoscopies. Whether or not instillation of 1,000 ml of Hartmann’s Solution was given intraperitonealy via the 5 mm insufflator port of laparoscopes at the end of the procedure was monitored. Pain scores at 4 h, 24 h, and 72 h after surgery were evaluated. There was no significant difference in the pain scores. 95% confidence intervals were determined for the differences between means assuming equal variance at 4 h (−1.7 to 1.8), 24 h (−1.9 to 1.9), and 72 h (−2.1 to 0.8) postoperatively. This small study suggests that the instillation of Hartmann’s Solution does not significantly reduce postoperative pain.

Four experiments investigated the acoustical correlates of similarity and categorization judgments of environmental sounds. In Experiment 1, similarity ratings were obtained from pairwise comparisons of recordings of 50 environmental sounds. A three-dimensional multidimensional scaling (MDS) solution showed three distinct clusterings of the sounds, which included harmonic sounds, discrete impact sounds, and continuous sounds. Furthermore, sounds from similar sources tended to be in close proximity to each other in the MDS space. The orderings of the sounds on the individual dimensions of the solution were well predicted by linear combinations of acoustic variables, such as harmonicity, amount of silence, and modulation depth. The orderings of sounds also correlated significantly with MDS solutions for similarity ratings of imagined sounds and for imagined sources of sounds, obtained in Experiments 2 and 3--as was the case for free categorization of the 50 sounds (Experiment 4)--although the categorization data were less well predicted by acoustic features than were the similarity data.

It has been known for some time that the immune system can recognise growing tumours, and that tumours may respond by modulation of molecules, which make them resistant to further attack. Expression, over-expression, or loss of these molecules may function as markers of tumour progression and prognosis. Among such molecules are the membrane-bound complement regulatory proteins (mCRP), which protect cells from bystander attack by autologous complement. These include CD59 (protectin), which prevents formation of the MAC complex in the terminal stages of complement activation. In the present study, we evaluated immunohistochemical expression of CD59 in a series of over 460 well-characterised colorectal cancers using tissue microarrays (TMA), and related this information to known tumour and patient variables and to survival. The CD59 expression was observed in 69 (15%) of cases overall, and was significantly associated with tumour grade. In contrast, no associations were noted with tumour site, stage or histological type. On survival analysis, a further correlation was observed between expression of CD59 by the colorectal tumours and a reduction in disease-specific patient survival. This observation was strongest for patients with early stage disease. However, a negative impact on survival was also seen in those patients with late stage disease. These results indicate that TMA linked to good clinicopathological databases with good long term follow up are useful tools for determining new prognostic indicators that can be used in future patient management. Immune surveillance may result in immune-editing that induces variable expression of a range of target antigens, and these may be useful prognostic markers. This study has identified CD59 expression as a marker of poor prognosis in colorectal cancer patients.

Tip-induced oxidative manipulation of conducting surfaces, e.g., Si and some metals, has conventionally been described by a field-induced anodic mechanism. Likewise, in the case of electrically conducting graphitic and diamond-like carbon (DLC) films, tip-induced conversion of carbon to CO2 was initially thought to be due to an ionisation process. There is now mounting evidence for thermal activation playing an important role. The state of the tip is a critical, but largely disregarded, factor in such experiments. The present project has been prepared and characterized by I–V analysis, tips with different initial characteristics (e.g., H-termination , Au-coating, native oxide). Likewise, several surfaces have been prepared (e.g., Si plus termination by either native or thermal oxide, or plus H-termination, DLC and Au), and also subjected to I–V analysis. The resultant point-contact characteristics were found to range from ohmic to non-ohmic (the latter due to either direct or Fowler–Nordheim tunnelling). The various combinations were tested with respect to oxidative yield and tip durability. It was found that the presence of a tunnelling barrier at the point of contact is essential for enhancing yield. Tip durability, on the other hand, is promoted by the barrier being located in the surface thus localizing thermal deposition in the surface rather than in the tip.

To determine the patterns of patellar motion in subjects without knee symptoms using dynamic magnetic resonance imaging (MRI). Patellar tracking MR examinations were performed on 50 asymptomatic volunteers. The presence and degree of lateral subluxation and tilt of the patella was assessed independently by three radiologists, and discrepancies resolved by consensus. Using the same criteria, the tracking pattern in 50 consecutive patients, recently referred for imaging assessment of anterior knee pain, was studied. Fifty volunteers (22 male, mean age 37 years) and 50 unmatched patients (15 male, mean age 25.5 years) were examined. Forty-one per cent of a total of 97 knees in the volunteer group showed evidence of lateral subluxation, which was either minimal (grade 1, 32%) or minor (grade 2, 9%). No volunteer demonstrated major (grade 3) subluxation; lateral tilt without translation of the patella was also seen (2%). In the patient group, higher grades of lateral subluxation were more common. Minimal (grade 1) lateralization is a common movement pattern of the patella on knee extension, and should be regarded as normal.

Nanocrystalline titanium dioxide (TiO2) particles were prepared by a modified alkoxide method under acidic conditions at temperatures ranging from 60°C to 90°C. The reaction temperature was used to control the crystalline phase of the TiO2 particles. At 60°C and 75°C rutile was formed whilst at 90°C anatase and brookite were formed.

Biopolymers in a confined solution environment will be subject to long-range electrostatic and short-range van der Waals interactions. The interactions between two model poly(amino acids), poly-l-lysine and poly-l-glutamic acid, in solution with a Si-oxide surface have been investigated. The model amino acids were adsorbed, or covalently coupled, to colloidal probes consisting of a micro-sphere attached to a force-sensing lever. The methodology was based on sensing interaction between the probe and a flat surface through carrying out force versus distance analysis with a scanning force microscope. The framework of the conventional DLVO theory was used to arrive at a qualitative description. The outcomes illustrate both repulsive and attractive long-range interactions that will hinder, or promote, transport of colloidal biospecies into the region of attractive short-range interactions at the physical interface. Large 'snap-on' distances were observed for some systems and were ascribed to compression of the 'soft' functionalised layers. Those observations and measurements of adhesion provided insights into conformation of the adsorbed species and strength of attachment. The results are relevant to design and functionality of Si-based microfluidics technology.

First-generation antihistamines are well-known to cause subjective drowsiness. A myriad of studies has also been published that suggest a clear relationship between the use of these drugs and objective performance impairment. Although not all of the tests used in these studies have been validated, the data are fairly consistent, and suggest a difference between earlier (first-generation) sedating antihistamines and the newer (second-generation) nonsedating antihistamines.

In a previous phase II trial of the synthetic topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), given as a 72-h infusion, we identified modest single agent activity of 9% in patients with previously untreated advanced non-small cell lung cancer (NSCLC). Preclinical studies suggested that a more prolonged continuous infusion of the drug might lead to greater antitumor activity. A phase I study recommended a phase II dose of 25 microg/m2/hr for 120 h (3000 microg/m2 over 5 days), administered for 2 consecutive weeks of a 3-week cycle. We utilized this schedule and enrolled 13 chemotherapy-naïve patients with Stage IIIB and IV NSCLC in this trial: median age 67 (range 57-74); 46% male; 92% stage IV; and median performance status 1. Twelve patients are available for response and toxicity evaluation after 2 cycles of therapy. One patient achieved a partial response. Four patients had stable disease while seven patients had progressive disease. Patients with stable or progressive disease after two cycles received no additional 9-AC, and were offered conventional chemotherapy. The median survival time was 10.2 months and the one-year survival rate 28% (95% confidence interval, 5-58%). Significant toxicities included myelosuppression, fatigue, and anorexia. One patient had grade 4 neutropenia following the first week of cycle 2, and did not receive additional therapy. There were no neutropenia-related infections. These data suggest that this prolonged schedule is unlikely to increase 9-AC's very modest activity in NSCLC above that seen with the simpler 72-h administration schedule. Further evaluation of 9-AC in NSCLC is not recommended.

Medicarpin and maackiain are antifungal pterocarpan phytoalexins produced by many legumes, and are thought to be important components of the defense response of these legumes to certain fungal pathogens. The Mak1 gene from the fungal pathogen Nectria haematococca encodes an FAD-dependent mono-oxygenase, known to specifically hydroxylate the phytoalexins medicarpin and maackiain, converting them to less fungitoxic derivatives. Two binary vector constructs were made containing the coding regions from two fungal clones, a Mak1 cDNA (intronless) and a genomic (including three fungal introns) clone, regulated by an enhanced cauliflower mosaic virus 35S promoter. The constructs were introduced into tobacco to check for expression of active fungal enzyme in plant cells and for splicing of fungal introns. Leaves of tobacco plants transformed with the Mak1 cDNA construct readily metabolized infiltrated medicarpin to 1a-hydroxymedicarpin, indicating high levels of active enzyme. RT-PCR analysis of tobacco plants transformed with the Mak1 genomic construct indicated no processing of Mak1 introns, and no Mak1 activity was detected in these plants. When using plants containing the Mak1 cDNA construct, immunolocalization with a Mak1-specific antibody together with cellular fractionation indicated that Mak1 protein accumulated in the plant cytoplasm, associated with endoplasmic reticulum membranes; medicarpin biosynthetic enzymes have been localized to the same subcellular region. The Mak1 cDNA construct is therefore suitable for use in studies to selectively eliminate medicarpin accumulation to assess the relative importance of medicarpin in the antifungal defense mechanisms of alfalfa and other legumes.