Knowledge, attitudes and practices towards malaria diagnostics among healthcare providers and healthcare-seekers in Kondoa district, Tanzania: a multi-methodological situation analysis.

BACKGROUND Despite the large-scale rollout of malaria rapid diagnostic tests (RDTs) in Tanzania, many healthcare providers (HCPs) continue using blood film microscopy (BFM) and clinical examination to diagnose malaria, which can increase the risk of mal-diagnosis and over-prescribing of anti-malarials. Patients disregarding negative test results and self-treating exacerbate the problem. This study explored the knowledge, attitudes and practices of HCPs and healthcare-seekers regarding RDTs in comparison to BFM testing. METHODS A situational analysis was, therefore, conducted in Kondoa District, Dodoma Region, Tanzania. A multi-methodological approach was adopted including (i) a health facility inventory and screening of logbooks from May 2013 to April 2014 with 77,126 patient entries from 33 health facilities; (ii) a survey of 40 HCPs offering malaria services; and iii) a survey of 309 randomly selected household members from the facilities' catchment area. Surveys took place in April and May 2014. RESULTS Health facility records revealed that out of 77,126 patient entries, 22% (n = 17,235) obtained a malaria diagnosis. Of those, 45% were made with BFM, 33% with RDT and 22% with clinical diagnosis. A higher rate of positive diagnoses was observed with BFM compared with RDT (71% vs 14%). In the HCP survey, 48% preferred using BFM for malaria testing, while 52% preferred RDT. Faced with a negative RDT result for a patient presenting with symptoms typical for malaria, 25% of HCPs stated they would confirm the result with a microscopy test, 70% would advise or perform a clinical diagnosis and 18% would prescribe anti-malarials. Interviews with household members revealed a preference for microscopy testing (58%) over RDT (23%), if presented with malaria symptoms. For participants familiar with both tests, a second opinion was desired in 45% after a negative microscopy result and in 90% after an RDT. CONCLUSIONS Non-adherence to negative diagnostics by HCPs and patients continues to be a concern. Frequent training and supportive supervision for HCPs diagnosing and treating malaria and non-malaria febrile illnesses is essential to offer quality services that can instil confidence in HCPs and patients alike. The introduction of new diagnostic devices should be paired with context-specific behaviour change interventions targeting healthcare-seekers and healthcare providers

Orbital Magnetic Dipole Mode in Deformed Clusters: A Fully Microscopic Analysis

The orbital M1 collective mode predicted for deformed clusters in a schematic model is studied in a self-consistent random-phase-approximation approach which fully exploits the shell structure of the clusters. The microscopic mechanism of the excitation is clarified and the close correlation with E2 mode established. The study shows that the M1 strength of the mode is fragmented over a large energy interval. In spite of that, the fraction remaining at low energy, well below the overwhelming dipole plasmon resonance, is comparable to the strength predicted in the schematic model. The importance of this result in view of future experiments is stressed.Comment: 10 pages, 3 Postscript figures, uses revte

T-cell epitopes of the major peach allergen, Pru p 3: Identification and differential T-cell response of peach-allergic and non-allergic subjects

Lipid transfer proteins (LTPs), particularly peach Pru p 3, are the most relevant plant food allergens in the South of Europe, and, therefore, their allergic properties have been extensively studied. However, neither T-cell epitopes nor their effect on the patients’ T-cell response has been investigated in any member of the LTP panallergen family. The objective of the present study was to map the major T-cell epitopes of Pru p 3, as well as to evaluate their induced T-cell response in peach-allergic versus control subjects. Thus, peripheral blood mononuclear cells (PBMCs) from 18 peach-allergic patients and Pru p 3-specific T-cell lines (TCLs) from 9 of them were cultured with Pru p 3 and with a panel of 17 derived peptides (10-mer overlapping in 5 amino acids representing the full sequence of Pru p 3). Proliferation in 5-day assays was carried out via tritiated-thymidine incorporation, while IL4 and IFNγ production was assessed via sandwich enzyme-linked immunosorbent tests (ELISA) of TCL culture supernatants. The results were compared to those obtained from 10 non-peach allergic control volunteers. Two consecutive peptides showed the highest activation capacity. About 74% of PBMCs and TCLs recognized them, forming a single T-epitope: Pru p 365–80. Additionally, other specific T-cell epitopes were observed. Pru p 325–35 was detected by more than 60% of TCLs from peach-allergic patients, and Pru p 345–55 only activated PBMCs from control subjects. Interestingly, TCLs from patients were associated with a Th2-type, whereas control TCLs presented a Th1-type cytokine response. The major immunogenic T-cell epitope identified in Pru p 3, Pru p 365–80, is a good candidate to develop new vaccines for hypersensitivity reactions associated with LTP allergens from Rosaceae fruits

Correlation of sensitizing capacity and T-cell recognition within the Bet v 1 family

BackgroundBet v 1 is the main sensitizing allergen in birch pollen. Like many other major allergens, it contains an immunodominant T cell–activating region (Bet v 1142-156). Api g 1, the Bet v 1 homolog in celery, lacks the ability to sensitize and is devoid of major T-cell epitopes.ObjectiveWe analyzed the T-cell epitopes of Mal d 1, the nonsensitizing Bet v 1 homolog in apple, and assessed possible differences in uptake and antigen processing of Bet v 1, Api g 1, and Mal d 1.MethodsFor epitope mapping, Mal d 1–specific T-cell lines were stimulated with overlapping synthetic 12-mer peptides. The surface binding, internalization, and intracellular degradation of Bet v 1, Api g 1, and Mal d 1 by antigen-presenting cells were compared by using flow cytometry. All proteins were digested with endolysosomal extracts, and the resulting peptides were identified by means of mass spectrometry. The binding of Bet v 1142-156 and the homologous region in Mal d 1 by HLA class II molecules was analyzed in silico.ResultsLike Api g 1, Mal d 1 lacked dominant T-cell epitopes. The degree of surface binding and the kinetics of uptake and endolysosomal degradation of Bet v 1, Api g 1, and Mal d 1 were comparable. Endolysosomal degradation of Bet v 1 and Mal d 1 resulted in very similar fragments. The Bet v 1142-156 and Mal d 1141-155 regions showed no striking difference in their binding affinities to the most frequent HLA-DR alleles.ConclusionThe sensitizing activity of different Bet v 1 homologs correlates with the presence of immunodominant T-cell epitopes. However, the presence of Bet v 1142-156 is not conferred by differential antigen processing

Constrained Willmore Surfaces

Constrained Willmore surfaces are conformal immersions of Riemann surfaces that are critical points of the Willmore energy $W=\int H^2$ under compactly supported infinitesimal conformal variations. Examples include all constant mean curvature surfaces in space forms. In this paper we investigate more generally the critical points of arbitrary geometric functionals on the space of immersions under the constraint that the admissible variations infinitesimally preserve the conformal structure. Besides constrained Willmore surfaces we discuss in some detail examples of constrained minimal and volume critical surfaces, the critical points of the area and enclosed volume functional under the conformal constraint.Comment: 17 pages, 8 figures; v2: Hopf tori added as an example, minor changes in presentation, numbering changed; v3: new abstract and appendix, several changes in presentatio

Universality of Symmetry and Mixed-symmetry Collective Nuclear States

The global correlation in the observed variation with mass number of the $E2$ and summed $M1$ transition strengths is examined for rare earth nuclei. It is shown that a theory of correlated $S$ and $D$ fermion pairs with a simple pairing plus quadrupole interaction leads naturally to this universality. Thus a unified and quantitative description emerges for low-lying quadrupole and dipole strengths.Comment: In press, Phys. Rev. Lett. 199

Investment case for two-year post university speciality training in family medicine in Tajikistan: how much is needed for continuing and scaling up the improved education of family doctors?

Background: A new two-year Post University Specialty Training (PUST) programme in family medicine was introduced to improve the quality of postgraduate speciality medical education in Tajikistan. Postgraduate education of family doctors (FDs) needs to be urgently scaled up, as 38% of FD positions in Tajikistan remained unfilled in 2018. Moreover, the international financial support for the PUST programme is ending. This investment case assesses the minimum funding needed for the continuation and scale-up of PUST and establishes the rationale for the investment in the light of a recent evaluation. Methods: The costs of the programme were calculated for 2018 and a scale-up forecast made for the period 2019-2023. The impact of the scale-up on the shortage of FDs was assessed. An evaluation using a Multiple Choice Questionnaire and Objective Structured Clinical Examination (OSCE) assessed and compared theoretical knowledge, clinical skills and competencies of PUST trained and conventionally trained FDs. Results: The annual costs of the programme were US$228,000 in 2018. The total investment needed for scaling up PUST from 31 new FDs in 2018 to 100 FD graduates each year by 2023 was US$ 802,000.However, when the retirement of FDs and population growth are considered, the scale-up will result only in maintaining the current level of FDs working and not solve the country's FD shortage. The PUST FDs demonstrated significantly better clinical skills than the conventionally trained interns, scoring 60 and 45% of OSCE points, respectively. Theoretical knowledge showed a similar trend; PUST FDs answered 44% and interns 38% of the questions correctly. Conclusions: The two-year PUST programme has clearly demonstrated it produces better skilled family doctors than the conventional one-year internship, albeit some enduring quality concerns do still prevail. The discontinuation of international support for PUST would be a major setback and risks potentially losing the benefits of the programme for family medicine and also other specialities. To guarantee the supply of adequately trained FDs and address the FD shortage, the PUST should be continued and scaled up. Therefore, it is essential that international support is extended and a gradual transition to sustainable national financing gets underway