Improving BOLD sensitivity with real-time multi-echo echo-planar imaging - Towards a cleaner neurofeedback signal

Real-time functional magnetic resonance imaging (rtfMRI) suffers from known issues related to T2*-weighted single-echo echo-planar imaging (EPI). These include image dropout in areas with increased local magnetic susceptibility susceptibility gradients; suboptimal whole-brain blood oxygen level-dependent (BOLD) contrast due to average T2*-weighting; and confounders like subject motion and physiology. During fMRI neurofeedback a metric calculated from real-time brain activity is presented visually to the subject in the scanner. To prevent sham feedback, new methods should focus on improving BOLD signal quality in real-time. In this work, presented as a poster at the 11th annual meeting of the ISMRM Benelux chapter (17 January 2019), we present our work on real-time multi-echo fMRI and its usefulness in increasing the temporal signal-to-noise ratio (tSNR) of rtfMRI

Signal processing with Levy information

Levy processes, which have stationary independent increments, are ideal for modelling the various types of noise that can arise in communication channels. If a Levy process admits exponential moments, then there exists a parametric family of measure changes called Esscher transformations. If the parameter is replaced with an independent random variable, the true value of which represents a "message", then under the transformed measure the original Levy process takes on the character of an "information process". In this paper we develop a theory of such Levy information processes. The underlying Levy process, which we call the fiducial process, represents the "noise type". Each such noise type is capable of carrying a message of a certain specification. A number of examples are worked out in detail, including information processes of the Brownian, Poisson, gamma, variance gamma, negative binomial, inverse Gaussian, and normal inverse Gaussian type. Although in general there is no additive decomposition of information into signal and noise, one is led nevertheless for each noise type to a well-defined scheme for signal detection and enhancement relevant to a variety of practical situations.Comment: 27 pages. Version to appear in: Proc. R. Soc. London

Tuberculosis patients' reasons for, and suggestions to address non-uptake of HIV testing: a cross-sectional study in the Free State Province, South Africa

<p>Abstract</p> <p>Background</p> <p>South Africa endorses the global policy shift from primarily client-initiated voluntary counselling and testing (VCT) to routine/provider-initiated testing and counselling (PITC). The reason for this policy shift has been to facilitate uptake of HIV testing amongst at-risk populations in high-prevalence settings. Despite ostensible implementation of routine/PITC, uptake amongst tuberculosis (TB) patients in this country remains a challenge. This study presents the reasons that non-tested TB patients offered for their refusal of HIV testing and reflects on all TB patients' suggestions as to how this situation may be alleviated.</p> <p>Methods</p> <p>In February-March 2008, a cross-sectional survey was conducted amongst 600 TB patients across 61 primary health care facilities in four sub-districts in the Free State. Patient selection was done proportionally to the numbers registered at each facility in 2007. Data were subjected to bivariate tests and content analysis of open-ended questions.</p> <p>Results</p> <p>Almost one-third (32.5%) of the respondents reported that they had not undertaken HIV testing, with the most often offered explanation being that they were '<it>undecided</it>' (37.0%). Other self-reported reasons for non-uptake included: fear (e.g. of testing HIV-positive, 19.0%); perception of being at low risk of HIV infection (13.4%); desire first to deal with TB 'on its own' (12.5%); and because HIV testing had not been offered to them (12.0%). Many patients expressed the need for support and motivation not only from health care workers (33.3%), but also from their significant others (56.6%). Patients further expressed a need for (increased) dissemination of TB-HIV information by health care workers (46.1%).</p> <p>Conclusions</p> <p>Patients did not undergo HIV testing for various patient-/individual-related reasons. Non-uptake of HIV testing was also due to health system limitations such as the non-offer of HIV testing. Other measures may be necessary to supplement routine/provider-initiation of HIV testing. From the TB patient's perspective, there is a need for (improved) dissemination of information on the TB-HIV link. Patients also require (repeated) motivation and support to undergo HIV testing, the onus for which rests not only on the public health authority and health care workers, but also on other people in the patients' social support networks.</p

Constraints to Implementing the Essential Health Package in Malawi

Increasingly seen as a useful tool of health policy, Essential or Minimal Health Packages direct resources to interventions that aim to address the local burden of disease and be cost-effective. Less attention has been paid to the delivery mechanisms for such interventions. This study aimed to assess the degree to which the Essential Health Package (EHP) in Malawi was available to its population and what health system constraints impeded its full implementation. The first phase of this study comprised a survey of all facilities in three districts including interviews with all managers and clinical staff. In the second and third phase, results were discussed with District Health Management Teams and national level stakeholders, respectively, including representatives of the Ministry of Health, Central Medical Stores, donors and NGOs. The EHP in Malawi is focussing on the local burden of disease; however, key constraints to its successful implementation included a widespread shortage of staff due to vacancies but also caused by frequent trainings and meetings (only 48% of expected man days of clinical staff were available; training and meetings represented 57% of all absences in health centres). Despite the training, the percentage of health workers aware of vital diagnostic and therapeutic approaches to EHP conditions was weak. Another major constraint was shortages of vital drugs at all levels of facilities (e.g. Cotrimoxazole was sufficiently available to treat the average number of patients in only 27% of health centres). Although a few health workers noted some improvement in infrastructure and working conditions, they still considered them to be widely inadequate. In Malawi, as in similar resource poor countries, greater attention needs to be given to the health system constraints to delivering health care. Removal of these constraints should receive priority over the considerable focus on the development and implementation of essential packages of interventions

Outer membrane utilisomes mediate glycan uptake in gut Bacteroidetes

Bacteroidetes are abundant members of the human microbiota, utilizing a myriad of diet- and host-derived glycans in the distal gut1. Glycan uptake across the bacterial outer membrane of these bacteria is mediated by SusCD protein complexes, comprising a membrane-embedded barrel and a lipoprotein lid, which is thought to open and close to facilitate substrate binding and transport. However, surface-exposed glycan-binding proteins and glycoside hydrolases also play critical roles in the capture, processing and transport of large glycan chains. The interactions between these components in the outer membrane are poorly understood, despite being crucial for nutrient acquisition by our colonic microbiota. Here we show that for both the levan and dextran utilization systems of Bacteroides thetaiotaomicron, the additional outer membrane components assemble on the core SusCD transporter, forming stable glycan-utilizing machines that we term utilisomes. Single-particle cryogenic electron microscopy structures in the absence and presence of substrate reveal concerted conformational changes that demonstrate the mechanism of substrate capture, and rationalize the role of each component in the utilisome

Integrating innovations:a qualitative analysis of referral non-completion among rapid diagnostic test-positive patients in Uganda's human African trypanosomiasis elimination programme

BACKGROUND: The recent development of rapid diagnostic tests (RDTs) for human African trypanosomiasis (HAT) enables elimination programmes to decentralise serological screening services to frontline health facilities. However, patients must still undertake multiple onwards referral steps to either be confirmed or discounted as cases. Accurate surveillance thus relies not only on the performance of diagnostic technologies but also on referral support structures and patient decisions. This study explored why some RDT-positive suspects failed to complete the diagnostic referral process in West Nile, Uganda. METHODS: Between August 2013 and June 2015, 85% (295/346) people who screened RDT-positive were examined by microscopy at least once; 10 cases were detected. We interviewed 20 RDT-positive suspects who had not completed referral (16 who had not presented for their first microscopy examination, and 4 who had not returned for a second to dismiss them as cases after receiving discordant [RDT-positive, but microscopy-negative results]). Interviews were analysed thematically to examine experiences of each step of the referral process. RESULTS: Poor provider communication about HAT RDT results helped explain non-completion of referrals in our sample. Most patients were unaware they were tested for HAT until receiving results, and some did not know they had screened positive. While HAT testing and treatment is free, anticipated costs for transportation and ancillary health services fees deterred many. Most expected a positive RDT result would lead to HAT treatment. RDT results that failed to provide a definitive diagnosis without further testing led some to question the expertise of health workers. For the four individuals who missed their second examination, complying with repeat referral requests was less attractive when no alternative diagnostic advice or treatment was given. CONCLUSIONS: An RDT-based surveillance strategy that relies on referral through all levels of the health system is inevitably subject to its limitations. In Uganda, a key structural weakness was poor provider communication about the possibility of discordant HAT test results, which is the most common outcome for serological RDT suspects in a HAT elimination programme. Patient misunderstanding of referral rationale risks harming trust in the whole system and should be addressed in elimination programmes

Identification of d -arabinan-degrading enzymes in mycobacteria

Bacterial cell growth and division require the coordinated action of enzymes that synthesize and degrade cell wall polymers. Here, we identify enzymes that cleave the D-arabinan core of arabinogalactan, an unusual component of the cell wall of Mycobacterium tuberculosis and other mycobacteria. We screened 14 human gut-derived Bacteroidetes for arabinogalactan-degrading activities and identified four families of glycoside hydrolases with activity against the D-arabinan or D-galactan components of arabinogalactan. Using one of these isolates with exo-D-galactofuranosidase activity, we generated enriched D-arabinan and used it to identify a strain of Dysgonomonas gadei as a D-arabinan degrader. This enabled the discovery of endo- and exo-acting enzymes that cleave D-arabinan, including members of the DUF2961 family (GH172) and a family of glycoside hydrolases (DUF4185/GH183) that display endo-D-arabinofuranase activity and are conserved in mycobacteria and other microbes. Mycobacterial genomes encode two conserved endo-D-arabinanases with different preferences for the D-arabinan-containing cell wall components arabinogalactan and lipoarabinomannan, suggesting they are important for cell wall modification and/or degradation. The discovery of these enzymes will support future studies into the structure and function of the mycobacterial cell wall