Quantifying water diffusion in high-viscosity and glassy aqueous solutions using a Raman isotope tracer method

Recent research suggests that under certain temperature and relative humidity conditions atmospheric aerosol may be present in the form of a glassy solid. In order to understand the impacts that this may have on aerosol–cloud interactions and atmospheric chemistry, knowledge of water diffusion within such aerosol particles is required. Here, a method is described in which Raman spectroscopy is used to observe D2O diffusion in high-viscosity aqueous solutions, enabling a quantitative assessment of water diffusion coefficients, Dwater, as a function of relative humidity. Results for sucrose solutions compare well with literature data at 23.5 ± 0.3 °C, and demonstrate that water diffusion is slow (Dwater ~5 × 10−17 m2 s−1), but not arrested, just below the glass transition at a water activity of 0.2. Room temperature water diffusion coefficients are also presented for aqueous levoglucosan and an aqueous mixture of raffinose, dicarboxylic acids and ammonium sulphate: at low humidity, diffusion is retarded but still occurs on millisecond to second timescales in atmospherically relevant-sized particles. The effect of gel formation on diffusion in magnesium sulfate solutions is shown to be markedly different from the gradual decrease in diffusion coefficients of highly viscous liquids. We show that using the Stokes–Einstein equation to determine diffusion timescales from viscosity leads to values which are more than 5 orders of magnitude too big, which emphasises the need to make measurements of diffusion coefficients. In addition, comparison of bounce fraction data for levoglucosan with measured diffusion data reveals that even when particles bounce the diffusion timescales for water are a fraction of a second for a 100 nm particle. This suggests a high bounce fraction does not necessarily indicate retarded water diffusion

Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS)

.Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties

CAD in mammography: lesion-level versus case-level analysis of the effects of prompts on human decisions

Object: To understand decision processes in CAD-supported breast screening by analysing how prompts affect readers’ judgements of individual mammographic features (lesions). To this end we analysed hitherto unexamined details of reports completed by mammogram readers in an earlier evaluation of a CAD tool. Material and methods: Assessments of lesions were extracted from 5,839 reports for 59 cancer cases. Statistical analyses of these data focused on what features readers considered when recalling a cancer case and how readers reacted to CAD prompts. Results: About 13.5% of recall decisions were found to be caused by responses to features other than those indicating actual cancer. Effects of CAD: lesions were more likely to be examined if prompted; the presence of a prompt on a cancer increased the probability of both detection and recall especially for less accurate readers in subtler cases; lack of prompts made cancer features less likely to be detected; false prompts made non-cancer features more likely to be classified as cancer. Conclusion: The apparent lack of impact reported for CAD in some studies is plausibly due to CAD systematically affecting readers’ identification of individual features, in a beneficial way for certain combinations of readers and features and a damaging way for others. Mammogram readers do not ignore prompts. Methodologically, assessing CAD by numbers of recalled cancer cases may be misleading

Heterogeneous Ice Nucleation by Soufriere Hills Volcanic Ash Immersed in Water Droplets

Fine particles of ash emitted during volcanic eruptions may sporadically influence cloud properties on a regional or global scale as well as influencing the dynamics of volcanic clouds and the subsequent dispersion of volcanic aerosol and gases. It has been shown that volcanic ash can trigger ice nucleation, but ash from relatively few volcanoes has been studied for its ice nucleating ability. In this study we quantify the efficiency with which ash from the Soufriere Hills volcano on Montserrat nucleates ice when immersed in supercooled water droplets. Using an ash sample from the 11th February 2010 eruption, we report ice nucleating efficiencies from 246 to 265 K. This wide range of temperatures was achieved using two separate droplet freezing instruments, one employing nanolitre droplets, the other using microlitre droplets. Soufriere Hills volcanic ash was significantly more efficient than all other ash samples that have been previously examined. At present the reasons for these differences are not understood, but may be related to mineralogy, amorphous content and surface chemistry

Classifying the posture and activity of ewes and lambs using accelerometers and machine learning on a commercial flock

This is the final version. Available on open access from Elsevier via the DOI in this recordData Availability: A censored version of the data is available upon request.Early decision making in commercial livestock systems is key to maximising animal welfare and production. Detailed information on an animal’s phenotype is needed to facilitate this, but can be difficult to obtain in a commercial setting. Research into the use of bio-logging on sheep to continuously monitor individual behaviour and indirectly inform health and production has seen rapid growth in recent years. Much of this research, however, has been conducted on small numbers of animals in an experimental setting and over limited time periods. Previous studies have also focused on ewes and there has been little research on the potential of bio-logging for collecting behavioural data on lambs, despite clear potential relevance for production. The present study aimed to test the feasibility of deploying accelerometers on a commercial sheep flock at a key point in the annual production cycle (lambing), to validate the viability of automated monitoring of sheep behaviour in a commercial setting. Also, we aimed to develop robust machine learning algorithms that can classify both the posture and physical activity of adult sheep and lambs. We used a Random Forest machine learning algorithm to predict: two mutually exclusive postures in ewes and lambs (standing and lying), achieving average accuracies of 83.7% and 85.9% respectively; four mutually exclusive activities in ewes (grazing, ruminating, inactive and walking), achieving an average accuracy of 70.9%; and three mutually exclusive activities in lambs (inactive, suckling, walking), achieving an average accuracy of 80.8%. These performance accuracies on large numbers of individuals afford the opportunity to provide a detailed understanding of the daily activity budget of ewes and lambs. Monitoring changes in daily patterns across the annual production cycle while capturing changes in environmental conditions such as weather, day length, terrain and management could reveal key indicator metrics that may inform production and health and provide early warning systems for key issues in commercial flocks.Biotechnology & Biological Sciences Research Council (BBSRC

Integrating personality research and animal contest theory: aggressiveness in the green swordtail <i>Xiphophorus helleri</i>

&lt;p&gt;Aggression occurs when individuals compete over limiting resources. While theoretical studies have long placed a strong emphasis on context-specificity of aggression, there is increasing recognition that consistent behavioural differences exist among individuals, and that aggressiveness may be an important component of individual personality. Though empirical studies tend to focus on one aspect or the other, we suggest there is merit in modelling both within-and among-individual variation in agonistic behaviour simultaneously. Here, we demonstrate how this can be achieved using multivariate linear mixed effect models. Using data from repeated mirror trials and dyadic interactions of male green swordtails, &lt;i&gt;Xiphophorus helleri&lt;/i&gt;, we show repeatable components of (co)variation in a suite of agonistic behaviour that is broadly consistent with a major axis of variation in aggressiveness. We also show that observed focal behaviour is dependent on opponent effects, which can themselves be repeatable but were more generally found to be context specific. In particular, our models show that within-individual variation in agonistic behaviour is explained, at least in part, by the relative size of a live opponent as predicted by contest theory. Finally, we suggest several additional applications of the multivariate models demonstrated here. These include testing the recently queried functional equivalence of alternative experimental approaches, (e. g., mirror trials, dyadic interaction tests) for assaying individual aggressiveness.&lt;/p&gt

Inter-rater reliability of the Dysexecutive Questionnaire (DEX): comparative data from non-clinician respondents – all raters are not equal

Primary objective: The Dysexecutive Questionnaire (DEX) is used to obtain information about executive and emotional problems after neuropathology. The DEX is self-completed by the patient (DEX-S) and an independent rater such as a family member (DEX-I). This study examined the level of inter-rater agreement between either two or three non-clinician raters on the DEX-I in order to establish the reliability of DEX-I ratings. Methods and procedures: Family members and/or carers of 60 people with mixed neuropathology completed the DEX-I. For each patient, DEX-I ratings were obtained from either two or three raters who knew the person well prior to brain injury. Main outcomes and results: We obtained two independent-ratings for 60 patients and three independent-ratings for 36 patients. Intra-class correlations revealed that there was only a modest level of agreement for items, subscale and total DEX scores between raters for their particular family member. Several individual DEX items had low reliability and ratings for the emotion sub-scale had the lowest level of agreement. Conclusions: Independent DEX ratings completed by two or more non-clinician raters show only moderate correlation. Suggestions are made for improving the reliability of DEX-I ratings.</p

Implementation and Outcomes of Commercial Disease Management Programs in the United States: The Disease Management Outcomes Consolidation Survey

Despite widespread adoption of disease management (DM) programs by US health plans, gaps remain in the evidence for their benefit. The Disease Management Outcomes Consolidation Survey was designed to gather data on DM programs for commercial health plans, to assess program success and DM effectiveness. The questionnaire was mailed to 292 appropriate health plan contacts; 26 plans covering more than 14 million commercial members completed and returned the survey. Respondents reported that DM plays a significant and increasing role in their organizations. Key reasons for adopting DM were improving clinical outcomes, reducing medical costs and utilization, and improving member satisfaction. More respondents were highly satisfied with clinical results than with utilization or cost outcomes of their programs (46%, 17%, and 13%, respectively). Detailed results were analyzed for 57 DM programs with over 230,000 enrollees. Most responding plans offered DM programs for diabetes and asthma, with return on investment (ROI) ranging from 0.16:1 to 4:1. Weighted by number of enrollees per DM program, average ROI was 2.56:1 for asthma (n = 1,136 enrollees) and 1.98:1 for diabetes (n = 25,364). Most (but not all) respondents reported reduced hospital admissions, increasing rates of preventive care, and improved clinical measures. Few respondents provided detailed information about DM programs for other medical conditions, but most that did reported positive outcomes. Lack of standardized methodology was identified as a major barrier to in-house program evaluation. Although low response rate precluded drawing many general conclusions, a clear need emerged for more rigorous evaluation methods and greater standardization of outcomes measurement. (Disease Management 2005;8:253–264)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63399/1/dis.2005.8.253.pd

How Gaussian competition leads to lumpy or uniform species distributions

A central model in theoretical ecology considers the competition of a range of species for a broad spectrum of resources. Recent studies have shown that essentially two different outcomes are possible. Either the species surviving competition are more or less uniformly distributed over the resource spectrum, or their distribution is 'lumped' (or 'clumped'), consisting of clusters of species with similar resource use that are separated by gaps in resource space. Which of these outcomes will occur crucially depends on the competition kernel, which reflects the shape of the resource utilization pattern of the competing species. Most models considered in the literature assume a Gaussian competition kernel. This is unfortunate, since predictions based on such a Gaussian assumption are not robust. In fact, Gaussian kernels are a border case scenario, and slight deviations from this function can lead to either uniform or lumped species distributions. Here we illustrate the non-robustness of the Gaussian assumption by simulating different implementations of the standard competition model with constant carrying capacity. In this scenario, lumped species distributions can come about by secondary ecological or evolutionary mechanisms or by details of the numerical implementation of the model. We analyze the origin of this sensitivity and discuss it in the context of recent applications of the model.Comment: 11 pages, 3 figures, revised versio

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac