PCR-Independent Detection of Bacterial Species-Specific 16S rRNA at 10 fM by a Pore-Blockage Sensor.

A PCR-free, optics-free device is used for the detection of Escherichia coli (E. coli) 16S rRNA at 10 fM, which corresponds to ~100-1000 colony forming units/mL (CFU/mL) depending on cellular rRNA levels. The development of a rapid, sensitive, and cost-effective nucleic acid detection platform is sought for the detection of pathogenic microbes in food, water and body fluids. Since 16S rRNA sequences are species specific and are present at high copy number in viable cells, these nucleic acids offer an attractive target for microbial pathogen detection schemes. Here, target 16S rRNA of E. coli at 10 fM concentration was detected against a total RNA background using a conceptually simple approach based on electromechanical signal transduction, whereby a step change reduction in ionic current through a pore indicates blockage by an electrophoretically mobilized bead-peptide nucleic acid probe conjugate hybridized to target nucleic acid. We investigated the concentration detection limit for bacterial species-specific 16S rRNA at 1 pM to 1 fM and found a limit of detection of 10 fM for our device, which is consistent with our previous finding with single-stranded DNA of similar length. In addition, no false positive responses were obtained with control RNA and no false negatives with target 16S rRNA present down to the limit of detection (LOD) of 10 fM. Thus, this detection scheme shows promise for integration into portable, low-cost systems for rapid detection of pathogenic microbes in food, water and body fluids

Army-NASA aircrew/aircraft integration program. Phase 5: A3I Man-Machine Integration Design and Analysis System (MIDAS) software concept document

This is the Software Concept Document for the Man-machine Integration Design and Analysis System (MIDAS) being developed as part of Phase V of the Army-NASA Aircrew/Aircraft Integration (A3I) Progam. The approach taken in this program since its inception in 1984 is that of incremental development with clearly defined phases. Phase 1 began in 1984 and subsequent phases have progressed at approximately 10-16 month intervals. Each phase of development consists of planning, setting requirements, preliminary design, detailed design, implementation, testing, demonstration and documentation. Phase 5 began with an off-site planning meeting in November, 1990. It is expected that Phase 5 development will be complete and ready for demonstration to invited visitors from industry, government and academia in May, 1992. This document, produced during the preliminary design period of Phase 5, is intended to record the top level design concept for MIDAS as it is currently conceived. This document has two main objectives: (1) to inform interested readers of the goals of the MIDAS Phase 5 development period, and (2) to serve as the initial version of the MIDAS design document which will be continuously updated as the design evolves. Since this document is written fairly early in the design period, many design issues still remain unresolved. Some of the unresolved issues are mentioned later in this document in the sections on specific components. Readers are cautioned that this is not a final design document and that, as the design of MIDAS matures, some of the design ideas recorded in this document will change. The final design will be documented in a detailed design document published after the demonstrations

Exploiting goal independence in the analysis of logic programs

This paper illustrates the use of a top-down framework to obtain goal independent analyses of logic programs, a task which is usually associated with the bottom-up approach. While it is well known that the bottomup approach can be used, through the magic set transformation, for goal dependent analysis, it is less known that the top-down approach can be used for goal independent analysis. The paper describes two ways of doing the latter. We show how the results of a goal independent analysis can be used to speed up subsequent goal dependent analyses. However this speed-up may result in a loss of precisión. The influence of domain characteristics on this precisión is discussed and an experimental evaluation using a generic top-down analyzer is described

Goal dependent vs goal independent analysis of logic programs

Goal independent analysis of logic programs is commonly discussed in the context of the bottom-up approach. However, while the literature is rich in descriptions of top-down analysers and their application, practical experience with bottom-up analysis is still in a preliminary stage. Moreover, the practical use of existing top-down frameworks for goal independent analysis has not been addressed in a practical system. We illustrate the efficient use of existing goal dependent, top-down frameworks for abstract interpretation in performing goal independent analyses of logic programs much the same as those usually derived from bottom-up frameworks. We present several optimizations for this flavour of top-down analysis. The approach is fully implemented within an existing top-down framework. Several implementation tradeoffs are discussed as well as the influence of domain characteristics. An experimental evaluation including a comparison with a bottom-up analysis for the domain Prop is presented. We conclude that the technique can offer advantages with respect to standard goal dependent analyses

Addressing Radiography Workforce Competence Gaps in Zambia: Insights into the Radiography Diploma Training Programme Using a Curriculum Mapping Approach

In Zambia, the radiography diploma programme has been offered since 1970 and has undergone only five reviews against an estimated ten [10] over 40 years. Such a situation can call into question the quality of radiography training. Curriculum evaluation is a key factor in ensuring quality standards of an educational training programme. The timely review ensures that curricula are in keeping with contemporary practice requirements. We analysed the 2014 radiography curriculum using a curriculum mapping approach to evaluate the stated objectives and their alignment to the educational domains and contemporary radiography practice requirements. Method: A case study design was used to explore the 2014 TEVETA radiography curriculum. Content analysis was used to identify curriculum learning objectives. A framework based on Harden’s curriculum mapping approach was developed. The first phase involved analysis of the curriculum content against the educational domains [i.e. cognitive, psychomotor, and affective domains, respectively]. The second phase involved comparing the stated learning outcomes with contemporary radiography practices. Results: A total of 90 learning outcomes were identified. The analysis revealed that 80% [N=72] of all the stated objectives were cognitive, while only 13% and 7% were psychomotor and affective, respectively. Furthermore, over 70% were pitched at the lower-order skills level of Dave’s taxonomy. In terms of radiographer competence, 55% [N=40] were attributed to technical skills. However, more than 90% of the technical competences were knowledge components and 10% actual psychomotor skills. Conclusion: A curriculum mapping approach was useful in analysing the current Zambian radiography diploma curriculum. The overemphasis on lower-order cognitive and psychomotor competence in the curriculum calls into question the technical readiness of new graduates to effectively perform at the expected level of proficiency in the workplace. Findings of this study provide valuable information that can be used for reviewing the curriculum to make the training more responsive to contemporary radiography practice demands

A Comparison of the Arbitrary Set Fifty Percent Pass Mark Standard and Grade Point Average Attainment for Pharmacy Students at the University of Zambia: Implications for High-stakes decisions in Assessments

In many higher learning institutions and Health Professions Education (HPE) programmes in particular, there exists varying standard setting methods for assessment, certification and graduation of students’ academic performance. In Zambia, the historic arbitrary set 50% pass-fail standard is predominant in most health professions’ training programmes. Scientific validation of this practice, however, remains scarce. The aim of this study was to compare the academic performance on the historic arbitrary set 50% pass-fail standard to the Grade Point Average (GPA) score attainment for pharmacy students examined between 2013 and 2017 at the University of Zambia. A cross-sectional study was conducted with a total of 445 randomly selected final examination results for undergraduate pharmacy students examined between 2013 and 2017 at the University of Zambia. The data was analysed using Stata 13 and GraphPad Prism 5.  For all the statistical tests conducted, normality of the data was checked using the Shapiro-Wilk test. There was statistically significant difference between the historic arbitrary set 50% pass-fail standard and the course-specific examination composite score attainment in all the courses (P<0.0001). Additionally, there was a statistically significant difference between the examinees’ GPA score attained and the acceptable GPA score of 3.0 (Median GPA 1.75; IQR: 0.75-2.25 and 1.67; IQR: 1.0-2.0) for the fourth and fifth-year examinees respectively). The comparison of the academic performance on the arbitrary 50% pass-fail standard and GPA score attainment for pharmacy students revealed that despite students demonstrating ability to attain high course-specific composite scores using the arbitrary set 50% pass-fail standard, the attained median GPA score was statistically significantly less than the minimum acceptable GPA score of 3.0. While the 50% pass-fail standards’ precision to detect academic performance maybe questioned, the findings suggests that the incorporation of a credit point and GPA system for making assessment decisions to rate students, certification and graduation requirements in Health Professions Education may offer better precision and prediction to detect academic performance and competency attainment

Improving abstract interpretations by combining domains

This article considers static analysis based on abstract interpretation of logic programs over combined domains. It is known that analyses over combined domains provide more information potentially than obtained by the independent analyses. However, the construction of a combined analysis often requires redefining the basic operations for the combined domain. A practical approach to maintain precision in combined analyses of logic programs which reuses the individual analyses and does not redefine the basic operations is illustrated. The advantages of the approach are that proofs of correctness for the new domains are not required and implementations can be reused. The approach is demonstrated by showing that a combined sharing analysis — constructed from "old" proposals — compares well with other "new" proposals suggested in recent literature both from the point of view of efficiency and accuracy

"Most of what they do, we cannot do!" How lay health workers respond to barriers to uptake and retention in HIV care among pregnant and breastfeeding mothers in Malawi

Background: In the era of Option B+ and 'treat all' policies for HIV, challenges to retention in care are well documented. In Malawi, several large community-facility linkage (CFL) models have emerged to address these challenges, training lay health workers (LHW) to support the national prevention of mother-to-child transmission (PMTCT) programme. This qualitative study sought to examine how PMTCT LHW deployed by Malawi's three most prevalent CFL models respond to known barriers to access and retention to antiretroviral therapy (ART) and PMTCT. Methods: We conducted a qualitative study, including 43 semi-structured interviews with PMTCT clients; 30 focus group discussions with Ministry of Health (MOH)-employed lay and professional providers and PMTCT LHWs; a facility CFL survey and 2–4 hours of onsite observation at each of 8 sites and in-depth interviews with 13 programme coordinators and MOH officials. Thematic analysis was used, combining inductive and deductive approaches. Results: Across all three models, PMTCT LHWs carried out a number of 'targeted' activities that respond directly to a range of known barriers to ART uptake and retention. These include: (i) fulfilling counselling and educational functions that responded to women's fears and uncertainties; (ii) enhancing women's social connectedness and participation in their own care and (iii) strengthening service function by helping clinic-based providers carry out duties more efficiently and effectively. Beyond absorbing workload or improving efficiency, however, PMTCT LHWs supported uptake and retention through foundational but often intangible work to strengthen CFL, including via efforts to strengthen facility-side responsiveness, and build community members' recognition of and trust in services. Conclusion: PMTCT LHWs in each of the CFL models examined, addressed social, cultural and health system factors influencing client access to, and engagement with, HIV care and treatment. Findings underscore the importance of person-centred design in the 'treat-all' era and the contribution LHWs can make to this, but foreground the challenges of achieving person-centredness in the context of an under-resourced health system. Further work to understand the governance and sustainability of these project-funded CFL models and LHW cadres is now urgently required

Prevalence of Transmitted HIV Drug Resistance Among Newly Diagnosed Antiretroviral Therapy-Naive Pregnant Women in Lilongwe and Blantyre, Malawi

In 2006, a survey of transmitted human immunodeficiency virus (HIV) drug resistance (TDR) was conducted in Lilongwe, Malawi. The survey followed the World Health Organization method to classify TDR to nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) among primigravid women aged <25 years. Results of the 2006 survey showed <5% TDR in all drug classes. In 2009, TDR surveys using the same method were repeated in Lilongwe and expanded to Blantyre. Findings show that in Lilongwe TDR to NRTIs and PIs was <5%, whereas TDR to NNRTIs was 5%-15%. In Blantyre, TDR was <5% to all drug classes. Observed moderate TDR in Lilongwe is cause for concern and signals the need for closer monitoring of Malawi's antiretroviral therapy progra

Activation of Human Complement System by Dextran-Coated Iron Oxide Nanoparticles Is Not Affected by Dextran/Fe Ratio, Hydroxyl Modifications, and Crosslinking

While having tremendous potential as therapeutic and imaging tools, the clinical use of engineered nanoparticles has been associated with serious safety concerns. Activation of the complement cascade and release of proinflammatory factors C3a and C5a may contribute to infusion-related reactions, whereas opsonization with C3 fragments promotes rapid recognition and clearance of nanomaterials by mononuclear phagocytes. We used dextran-coated superparamagnetic iron oxide nanoparticles (SPIO), which are potent activators of the complement system, to study the role of nanoparticle surface chemistry in inciting complement in human serum. Using complement inhibitors and measuring levels of fluid phase markers (sC5b-9, C5a and Bb), we found that the majority of human complement activation by SPIO is through the alternative pathway (AP). SPIO prepared with high dextran/iron ratio showed some complement activation via calcium-sensitive pathways, but the AP was responsible for the bulk of complement activation and amplification. Activation via the AP required properdin, the positive regulator of the alternative C3bBb convertase. Modification of sugar alcohols of dextran with alkylating, acylating, or crosslinking agents did not overcome complement activation and C3 opsonization. These data demonstrate that human complement activation is independent of dextran modification of SPIO and suggest a crucial role of the AP in immune recognition of nano-assemblies in human serum