Pan-Plasmodium band sensitivity for Plasmodium falciparum detection in combination malaria rapid diagnostic tests and implications for clinical management

Background: Malaria rapid diagnostic tests (RDTs) are appropriate for case management, but persistent antigenaemia is a concern for HRP2-detecting RDTs in endemic areas. It has been suggested that pan-pLDH test bands on combination RDTs could be used to distinguish persistent antigenaemia from active Plasmodium falciparum infection, however this assumes all active infections produce positive results on both bands of RDTs, an assertion that has not been demonstrated. Methods: In this study, data generated during the WHO-FIND product testing programme for malaria RDTs was reviewed to investigate the reactivity of individual test bands against P. falciparum in 18 combination RDTs. Each product was tested against multiple wild-type P. falciparum only samples. Antigen levels were measured by quantitative ELISA for HRP2, pLDH and aldolase. Results: When tested against P. falciparum samples at 200 parasites/μL, 92% of RDTs were positive; 57% of these on both the P. falciparum and pan bands, while 43% were positive on the P. falciparum band only. There was a relationship between antigen concentration and band positivity; ≥4 ng/mL of HRP2 produced positive results in more than 95% of P. falciparum bands, while ≥45 ng/mL of pLDH was required for at least 90% of pan bands to be positive. Conclusions: In active P. falciparum infections it is common for combination RDTs to return a positive HRP2 band combined with a negative pan-pLDH band, and when both bands are positive, often the pan band is faint. Thus active infections could be missed if the presence of a HRP2 band in the absence of a pan band is interpreted as being caused solely by persistent antigenaemia.

Néstor-Guillermo Progeria Syndrome: a biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation

Background Premature aging syndromes recapitulate many aspects of natural aging and provide an insight into this phenomenon at a molecular and cellular level. The progeria syndromes appear to cause rapid aging through disruption of normal nuclear structure. Recently, a coding mutation (c.34G > A [p.A12T]) in the Barrier to Autointegration Factor 1 (BANF1) gene was identified as the genetic basis of Néstor-Guillermo Progeria syndrome (NGPS). This mutation was described to cause instability in the BANF1 protein, causing a disruption of the nuclear envelope structure. Results Here we demonstrate that the BANF1 A12T protein is indeed correctly folded, stable and that the observed phenotype, is likely due to the disruption of the DNA binding surface of the A12T mutant. We demonstrate, using biochemical assays, that the BANF1 A12T protein is impaired in its ability to bind DNA while its interaction with nuclear envelope proteins is unperturbed. Consistent with this, we demonstrate that ectopic expression of the mutant protein induces the NGPS cellular phenotype, while the protein localizes normally to the nuclear envelope. Conclusions Our study clarifies the role of the A12T mutation in NGPS patients, which will be of importance for understanding the development of the disease.

A semi-alternating direction method for a 2-D fractional FitzHugh–Nagumo monodomain model on an approximate irregular domain

A FitzHugh-Nagumo monodomain model has been used to describe the propagation of the electrical potential in heterogeneous cardiac tissue. In this paper, we consider a two-dimensional fractional FitzHugh-Nagumo monodomain model on an irregular domain. The model consists of a coupled Riesz space fractional nonlinear reaction-diffusion model and an ordinary differential equation, describing the ionic fluxes as a function of the membrane potential. Secondly, we use a decoupling technique and focus on solving the Riesz space fractional nonlinear reaction-diffusion model. A novel spatially second-order accurate semi-implicit alternating direction method (SIADM) for this model on an approximate irregular domain is proposed. Thirdly, stability and convergence of the SIADM are proved. Finally, some numerical examples are given to support our theoretical analysis and these numerical techniques are employed to simulate a two-dimensional fractional Fitzhugh-Nagumo model on both an approximate circular and an approximate irregular domain.

Basic personal values underlie and give coherence to political values: A cross national study in 15 countries

Do the political values of the general public form a coherent system? What might be the source of coherence? We view political values as expressions, in the political domain, of more basic personal values. Basic personal values (e.g., security, achievement, benevolence, hedonism) are organized on a circular continuum that reflects their conflicting and compatible motivations. We theorize that this circular motivational structure also gives coherence to political values. We assess this theorizing with data from 15 countries, using eight core political values (e.g., free enterprise, law and order) and ten basic personal values. We specify the underlying basic values expected to promote or oppose each political value. We offer different hypotheses for the 12 non-communist and three post-communist countries studied, where the political context suggests different meanings of a basic or political value. Correlation and regression analyses support almost all hypotheses. Moreover, basic values account for substantially more variance in political values than age, gender, education, and income. Multidimensional scaling analyses demonstrate graphically how the circular motivational continuum of basic personal values structures relations among core political values. This study strengthens the assumption that individual differences in basic personal values play a critical role in political thought.

Towards a consistent definition of a significant delta troponin with z-scores: A way out of chaos?

Aims: We assessed the diagnostic performance of z-scores to define a significant delta cardiac troponin (cTn) in a cohort of patients with well-defined clinical outcomes. Methods: We calculated z-scores, which are dependent on the analytical precision and biological variation, to report changes in cTn. We compared the diagnostic performances of a relative delta (%Δ), actual delta (Δ), and z-scores in 762 emergency department patients with symptoms of suspected acute coronary syndrome. cTn was measured with sensitive cTnI (Beckman Coulter), highly sensitive cTnI (Abbott), and highly sensitive cTnT (Roche) assays. Results: Receiver operating characteristic analysis showed no statistically significant differences in the areas under the curve (AUC) of z-scores and Δ with both superior compared to %Δ for all three assays (p<0.001). The AUCs of z-scores measured with the Abbott hs-cTnI (0.955) and Roche hs-cTnT (0.922) assays were comparable to Beckman Coulter cTnI (0.933) (p=0.272 and 0.640, respectively). The individualized Δ cut-off values that were required to emulate a z-score of 1.96 were: Beckman Coulter cTnI 30 ng/l, Abbott hs-cTnI 20 ng/l, and Roche hs-cTnT 7 ng/l. Conclusions: z-scores allow the use of a single cut-off value at all cTn levels, for both cTnI and cTnT and for sensitive and highly sensitive assays, with comparable diagnostic performances. This strategy of reporting significant changes as z-scores may obviate the need for the empirical development of assay-specific cut-off rules to define significant troponin changes.

Household food insecurity, diet, and weight status in a disadvantaged district of Ho Chi Minh City, Vietnam: A cross-sectional study

Background Food security exists when all people, at all times, have physical, economic and socially acceptable access to safe, sufficient, and adequately nutritious food in order to meet their dietary needs for an active and healthy life. For high income countries and those experiencing the nutrition transition, food security is not only about the quantity of available food but also the nutritional quality as related to over- and under-nutrition. Vietnam is currently undergoing this nutrition transition, and as a result the relationship between food insecurity, socio-demographic factors and weight status is complex. The primary objective of this study was to therefore measure the prevalence of household food insecurity in a disadvantaged urban district in Ho Chi Minh City (HCMC) in Vietnam using a more comprehensive tool. This study also aims to examine the relationships between food insecurity and socio-demographic factors, weight status, and food intakes. Methods A cross-sectional study was conducted using multi-stage sampling. Adults who were mainly responsible for cooking were interviewed in 250 households. Data was collected on socioeconomic and demographic factors using previously validated tools. Food security was assessed using the Latin American and Caribbean Household Food Security Scale (ELCSA) tool and households were categorized as food secure or mildly, moderately or severely food insecure. Questions regarding food intake were based on routinely used and validated questions in HCMC, weight status was self-reported. Results Cronbach’s alpha coefficient was 0.87, showing the ELCSA had a good internal reliability. Approximately 34.4% of households were food insecure. Food insecurity was inversely related to total household income (OR = 0.09, 95% CI = 0.04 - 0.22) and fruit intakes (OR = 2.2, 95% CI 1.31 - 4.22). There was no association between weight and food security status. Conclusions Despite rapid industrialization and modernization, food insecurity remains an important public health issue in large urban areas of HCMC, suggesting that strategies to address food insecurity should be implemented in urban settings, and not just rural locations. Fruit consumption among food insecure households may be compromised because of financial difficulties, which may lead to poorer health outcomes particularly related to non-communicable disease prevention and management.

Improving out-domain PLDA speaker verification using unsupervised inter-dataset variability compensation approach

Experimental studies have found that when the state-of-the-art probabilistic linear discriminant analysis (PLDA) speaker verification systems are trained using out-domain data, it significantly affects speaker verification performance due to the mismatch between development data and evaluation data. To overcome this problem we propose a novel unsupervised inter dataset variability (IDV) compensation approach to compensate the dataset mismatch. IDV-compensated PLDA system achieves over 10% relative improvement in EER values over out-domain PLDA system by effectively compensating the mismatch between in-domain and out-domain data.

Influencers on quality of life as reported by people living with dementia in long-term care: A descriptive exploratory approach

Background Over half of the residents in long-term care have a diagnosis of dementia. Maintaining quality of life is important, as there is no cure for dementia. Quality of life may be used as a benchmark for caregiving, and can help to enhance respect for the person with dementia and to improve care provision. The purpose of this study was to describe quality of life as reported by people living with dementia in long-term care in terms of the influencers of, as well as the strategies needed, to improve quality of life. Methods A descriptive exploratory approach. A subsample of twelve residents across two Australian states from a national quantitative study on quality of life was interviewed. Data were analysed thematically from a realist perspective. The approach to the thematic analysis was inductive and data-driven. Results Three themes emerged in relation to influencers and strategies related to quality of life: (a) maintaining independence; (b) having something to do, and; (c) the importance of social interaction. Conclusions The findings highlight the importance of understanding individual resident needs and consideration of the complexity of living in large group living situations, in particular in regard to resident decision-making.

Turbulence and Mixing in the Environment: Multi-Device Study in a Sub-tropical Estuary

In an estuary, mixing and dispersion result from a combination of large-scale advection and smallscale turbulence, which are complex to estimate. The predictions of scalar transport and mixing are often inferred and rarely accurate, due to inadequate understanding of the contributions of these difference scales to estuarine recirculation. A multi-device field study was conducted in a small sub-tropical estuary under neap tide conditions with near-zero fresh water discharge for about 48 hours. During the study, acoustic Doppler velocimeters (ADV) were sampled at high frequency (50 Hz), while an acoustic Doppler current profiler (ADCP) and global positioning system (GPS) tracked drifters were used to obtain some lower frequency spatial distribution of the flow parameters within the estuary. The velocity measurements were complemented with some continuous measurement of water depth, conductivity, temperature and some other physiochemical parameters. Thorough quality control was carried out by implementation of relevant error removal filters on the individual data set to intercept spurious data. A triple decomposition (TD) technique was introduced to access the contributions of tides, resonance and ‘true’ turbulence in the flow field. The time series of mean flow measurements for both the ADCP and drifter were consistent with those of the mean ADV data when sampled within a similar spatial domain. The tidal scale fluctuation of velocity and water level were used to examine the response of the estuary to tidal inertial current. The channel exhibited a mixed type wave with a typical phase-lag between 0.035π– 0.116π. A striking feature of the ADV velocity data was the slow fluctuations, which exhibited large amplitudes of up to 50% of the tidal amplitude, particularly in slack waters. Such slow fluctuations were simultaneously observed in a number of physiochemical properties of the channel. The ensuing turbulence field showed some degree of anisotropy. For all ADV units, the horizontal turbulence ratio ranged between 0.4 and 0.9, and decreased towards the bed, while the vertical turbulence ratio was on average unity at z = 0.32 m and approximately 0.5 for the upper ADV (z = 0.55 m). The result of the statistical analysis suggested that the ebb phase turbulence field was dominated by eddies that evolved from ejection type process, while that of the flood phase contained mixed eddies with significant amount related to sweep type process. Over 65% of the skewness values fell within the range expected of a finite Gaussian distribution and the bulk of the excess kurtosis values (over 70%) fell within the range of -0.5 and +2. The TD technique described herein allowed the characterisation of a broader temporal scale of fluctuations of the high frequency data sampled within the durations of a few tidal cycles. The study provides characterisation of the ranges of fluctuation required for an accurate modelling of shallow water dispersion and mixing in a sub-tropical estuary.

Investigating in-domain data requirements for PLDA training

This paper analyzes the limitations upon the amount of in- domain (NIST SREs) data required for training a probabilistic linear discriminant analysis (PLDA) speaker verification system based on out-domain (Switchboard) total variability subspaces. By limiting the number of speakers, the number of sessions per speaker and the length of active speech per session available in the target domain for PLDA training, we investigated the relative effect of these three parameters on PLDA speaker verification performance in the NIST 2008 and NIST 2010 speaker recognition evaluation datasets. Experimental results indicate that while these parameters depend highly on each other, to beat out-domain PLDA training, more than 10 seconds of active speech should be available for at least 4 sessions/speaker for a minimum of 800 speakers. If further data is available, considerable improvement can be made over solely out-domain PLDA training.

Dataset-invariant covariance normalization for out-domain PLDA speaker verification

In this paper we introduce a novel domain-invariant covariance normalization (DICN) technique to relocate both in-domain and out-domain i-vectors into a third dataset-invariant space, providing an improvement for out-domain PLDA speaker verification with a very small number of unlabelled in-domain adaptation i-vectors. By capturing the dataset variance from a global mean using both development out-domain i-vectors and limited unlabelled in-domain i-vectors, we could obtain domain- invariant representations of PLDA training data. The DICN- compensated out-domain PLDA system is shown to perform as well as in-domain PLDA training with as few as 500 unlabelled in-domain i-vectors for NIST-2010 SRE and 2000 unlabelled in-domain i-vectors for NIST-2008 SRE, and considerable relative improvement over both out-domain and in-domain PLDA development if more are available.

Differential interaction between the C2B domain of synaptotagmin-I and the Drosophila stonedA and stonedB proteins

The stoned locus in Drosophila encodes two proteins StonedA (STNA) and StonedB (STNB), both of which have been suggested to act as adaptins in mediating synaptic vesicle recycling. A combination of immunological, genetic and biochemical studies have shown an interaction of STNA and STNB with the C2B domain of Synaptotagmin-I (SYT-1), an integral synaptic vesicle protein that mediates Ca2+-dependent exocytosis, as well as endocytosis. The C2B domain of SYT-1 contains an AP-2 binding site that controls the size of recycled vesicles, and a C-terminal tryptophan-containing motif that acts as an internalization signal. Investigation of SYT-1 mutations in Drosophila has shown that altering the Ca2+ binding region of the C2B domain, results in a reduction in the rate of vesicle recycling, implicating this region in SYT-I endocytosis. In this poster, we report the molecular dissection of the interactions between the STNA and STNB proteins and the C2B domain of SYT-1. Deletion of the AP-2 binding site decreased the binding of both STNA and STNB. However, C-terminal deletions of the C2B domain significantly increased STNB binding. In contrast, the same C-terminal deletions reduced the affinity of the C2B domain for STNA. The possible interactions of both STNB and STNA with the Ca2+ binding region of SYT-1 will be also investigated.

The dead poets society: The copyright term and the public domain

In a victory for corporate control of cultural heritage, the Supreme Court of the United States has rejected a constitutional challenge to the Sonny Bono Copyright Term Extension Act 1998 (U.S.) by a majority of seven to two. This paper evaluates the litigation in terms of policy debate in a number of discourses — history, intellectual property law, constitutional law and freedom of speech, cultural heritage, economics and competition policy, and international trade. It argues that the extension of the copyright term will inhibit the dissemination of cultural works through the use of new technologies — such as Eric Eldred's Eldritch Press and Project Gutenberg. It concludes that there is a need to resist the attempts of copyright owners to establish the Sonny Bono Copyright Term Extension Act 1998 (U.S.) as an international model for other jurisdictions — such as Australia.

Parameterization and reliability of single-leg balance test assessed with inertial sensors in stroke survivors: a cross-sectional study

Background and purpose There are no published studies on the parameterisation and reliability of the single-leg stance (SLS) test with inertial sensors in stroke patients. Purpose: to analyse the reliability (intra-observer/inter-observer) and sensitivity of inertial sensors used for the SLS test in stroke patients. Secondary objective: to compare the records of the two inertial sensors (trunk and lumbar) to detect any significant differences in the kinematic data obtained in the SLS test. Methods Design: cross-sectional study. While performing the SLS test, two inertial sensors were placed at lumbar (L5-S1) and trunk regions (T7–T8). Setting: Laboratory of Biomechanics (Health Science Faculty - University of Málaga). Participants: Four chronic stroke survivors (over 65 yrs old). Measurement: displacement and velocity, Rotation (X-axis), Flexion/Extension (Y-axis), Inclination (Z-axis); Resultant displacement and velocity (V): RV=(Vx2+Vy2+Vz2)−−−−−−−−−−−−−−−−−√ Along with SLS kinematic variables, descriptive analyses, differences between sensors locations and intra-observer and inter-observer reliability were also calculated. Results Differences between the sensors were significant only for left inclination velocity (p = 0.036) and extension displacement in the non-affected leg with eyes open (p = 0.038). Intra-observer reliability of the trunk sensor ranged from 0.889-0.921 for the displacement and 0.849-0.892 for velocity. Intra-observer reliability of the lumbar sensor was between 0.896-0.949 for the displacement and 0.873-0.894 for velocity. Inter-observer reliability of the trunk sensor was between 0.878-0.917 for the displacement and 0.847-0.884 for velocity. Inter-observer reliability of the lumbar sensor ranged from 0.870-0.940 for the displacement and 0.863-0.884 for velocity. Conclusion There were no significant differences between the kinematic records made by an inertial sensor during the development of the SLS testing between two inertial sensors placed in the lumbar and thoracic regions. In addition, inertial sensors. Have the potential to be reliable, valid and sensitive instruments for kinematic measurements during SLS testing but further research is needed.

The development and refinement of the practice domain framework as a conceptual tool for understanding and guiding social care practice

This study identified the common factors that influence social care practice across disciplines (such as social work and psychology), practice fields, and geographical contexts and further developed the Practice Domain Framework as an empirically-based conceptual framework to assist practitioners in understanding practice complexities. The framework has application in critical reflection, professional supervision, interdisciplinary understanding, teamwork, management, teaching and research. A mixed-methods design was used to identify the components and structure of the refined framework. Eighteen influential factors were identified and organised into eight domains: the Societal, Structural, Organisational, Practice Field, Professional Practice, Accountable Practice, Community of Place, and Personal.