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"Thompson, Joanne"
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Poemhood, our black revival : history, folklore & the Black experience: a young adult poetry anthology
Featuring contributions from an award-winning, bestselling group of Black voices, past and present, this powerful poetry anthology elicits vital conversations about race, belonging, history and faith to highlight Black joy and pain.
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Real-time PCR assays for detection and quantification of early P. falciparum gametocyte stages
The use of quantitative qRT-PCR assays for detection and quantification of late gametocyte stages has revealed the high transmission capacity of the human malaria parasite,
Plasmodium falciparum
. To understand how the parasite adjusts its transmission in response to in-host environmental conditions including antimalarials requires simultaneous quantification of early and late gametocytes. Here, we describe qRT-PCR assays that specifically detect and quantify early-stage
P. falciparum
gametocytes. The assays are based on expression of known early and late gametocyte genes and were developed using purified stage II and stage V gametocytes and tested in natural and controlled human infections. Genes
pfpeg4
and
pfg27
are specifically expressed at significant levels in early gametocytes with a limit of quantification of 190 and 390 gametocytes/mL, respectively. In infected volunteers, transcripts of
pfpeg4
and
pfg27
were detected shortly after the onset of blood stage infection. In natural infections, both early (
pfpeg4
/
pfg27
) and late gametocyte transcripts
(pfs25
) were detected in 71.2% of individuals, only early gametocyte transcripts in 12.6%, and only late gametocyte transcripts in 15.2%. The
pfpeg4
/
pfg27
qRT-PCR assays are sensitive and specific for quantification of circulating sexually committed ring stages/early gametocytes and can be used to increase our understanding of epidemiological processes that modulate
P. falciparum
transmission.
Journal Article
Does a screening checklist for complex health and social care needs have potential clinical usefulness for predicting unplanned hospital readmissions in intensive care survivors: development and prospective cohort study
ObjectivesIntensive care (ICU) survivors are at high risk of long-term physical and psychosocial problems. Unplanned hospital readmission rates are high, but the best way to triage patients for interventions is uncertain. We aimed to develop and evaluate a screening checklist to help predict subsequent readmissions or deaths.DesignA checklist for complex health and social care needs (CHSCNs) was developed based on previous research, comprising six items: multimorbidity; polypharmacy; frequent previous hospitalisations; mental health issues; fragile social circumstances and impaired activities of daily living. Patients were considered to have CHSCNs if two or more were present. We prospectively screened all ICU discharges for CHSCNs for 12 months.SettingICU, Royal Infirmary, Edinburgh, UK.ParticipantsICU survivors over a 12-month period (1 June 2018 and 31 May 2019).InterventionsNone.Outcome measureReadmission or death in the community within 3 months postindex hospital discharge.ResultsOf 1174 ICU survivors, 937 were discharged alive from the hospital. Of these 253 (27%) were classified as having CHSCNs. In total 28% (266/937) patients were readmitted (N=238) or died (N=28) within 3 months. Among CHSCNs patients 45% (n=115) patients were readmitted (N=105) or died (N=10). Patients without CHSCNs had a 22% readmission (N=133) or death (N=18) rate. The checklist had: sensitivity 43% (95% CI 37% to 49%), specificity 79% (95% CI 76% to 82%), positive predictive value 45% (95% CI 41% to 51%), and negative predictive value 78% (95% CI 76% to 80%). Relative risk of readmission/death for patients with CHSCNs was 2.06 (95% CI 1.69 to 2.50), indicating a pretest to post-test probability change of 28%–45%. The checklist demonstrated high inter-rater reliability (percentage agreement ≥87% for all domains; overall kappa, 0.84).ConclusionsEarly evaluation of a screening checklist for CHSCNs at ICU discharge suggests potential clinical usefulness, but this requires further evaluation as part of a care pathway.
Journal Article
Objective Assessment of Cough: An Early Marker of Response to Biological Therapies in Asthma?
Cough is an important symptom of asthma. The objective assessment of chronic cough has been enhanced by the development of ambulatory cough monitoring systems. Mepolizumab has been demonstrated to reduce exacerbations in eosinophilic asthmatics long-term. We evaluate the utility of objective cough count as an outcome measure in severe eosinophilic asthma treated with mepolizumab. Consecutive, consenting patients initiated on treatment with mepolizumab had a 24-h cough count recorded at baseline; this was repeated at 1, 3 and 6 months. Asthma control questionnaire (ACQ) scores and exacerbation frequency were also recorded. The mean 24-h cough count in 11 subjects (8 females, mean age 53.6 years) was 172.4 at baseline; at 1, 3 and 6 months following initiation of treatment this decreased to 101.4, 92 and 70.8, respectively (
p
< 0.02). Significant improvements were also observed in mean ACQ score (3–1.6,
p
< 0.01) and exacerbation frequency (5.5 per year – 1.3,
p
< 0.01). Objective cough measurement could be used as an early, precise and clinically relevant endpoint in assessing response to asthma therapy.
Journal Article
STABLE trial of spectacle provision and driving safety among myopic motorcycle users in Vietnam: study protocol for a stepped-wedge, cluster randomised trial
Background
Traffic crashes are the leading cause of death globally for people aged 5–29 years, with 90% of mortality occurring in low- and middle-income countries (LMICs). The STABLE (Slashing Two-wheeled Accidents by Leveraging Eyecare) trial was designed to determine whether providing spectacles could reduce risk among young myopic motorcycle users in Vietnam.
Methods
This investigator-masked, stepped-wedge, cluster randomised naturalistic driving trial will recruit 625 students aged 18–23 years, driving ≥ 50 km/week, with ≥ 1-year driving experience and using motorcycles as their primary means of transport, in 25 clusters of 25 students in Ho Chi Minh City, Vietnam. Motorcycles of consenting students who have failed self-testing on the WHOeyes app will be fitted with Data Acquisition Systems (DAS) with video cameras and accelerometers. Video clips (± 30 s) of events flagged by the accelerometer will be reviewed for crash and near-crash events per 1000 km driven (main outcome). Five clusters of 25 students will be randomly selected every 12 weeks to undergo ocular examination and an estimated 40% of these will have bilateral spherical equivalent < − 0.5 D, and better-eye presenting distance visual acuity < 6/12, correctable bilaterally to ≥ 6/7.5. They will be given free distance spectacles and their driving data before receiving spectacles will be analysed as the control condition and subsequent data as the intervention condition. Secondary outcomes include visual function, cost-effectiveness and self-reported crash events.
Discussion
STABLE will be the first randomised trial of vision interventions and driving safety in a LMIC.
Trial registration
ClinicalTrials.gov,
NCT05466955
. Initial registration: 20 July 2022, most recent update: 9 July 2024.
Journal Article
A Conserved TCRβ Signature Dominates a Highly Polyclonal T-Cell Expansion During the Acute Phase of a Murine Malaria Infection
CD4 + αβ T-cells are key mediators of the immune response to a first Plasmodium infection, undergoing extensive activation and splenic expansion during the acute phase of an infection. However, the clonality and clonal composition of this expansion has not previously been described. Using a comparative infection model, we sequenced the splenic CD4 + T-cell receptor repertoires generated over the time-course of a Plasmodium chabaudi infection. We show through repeat replicate experiments, single-cell RNA-seq, and analyses of independent RNA-seq data, that following a first infection - within a highly polyclonal expansion - T-effector repertoires are consistently dominated by TRBV3 gene usage. Clustering by sequence similarity, we find the same dominant clonal signature is expanded across replicates in the acute phase of an infection, revealing a conserved pathogen-specific T-cell response that is consistently a hallmark of a first infection, but not expanded upon re-challenge. Determining the host or parasite factors driving this conserved response may uncover novel immune targets for malaria therapeutic purposes.
Journal Article
Identification of candidate transmission-blocking antigen genes in Theileria annulata and related vector-borne apicomplexan parasites
Background
Vector-borne apicomplexan parasites are a major cause of mortality and morbidity to humans and livestock globally. The most important disease syndromes caused by these parasites are malaria, babesiosis and theileriosis. Strategies for control often target parasite stages in the mammalian host that cause disease, but this can result in reservoir infections that promote pathogen transmission and generate economic loss. Optimal control strategies should protect against clinical disease, block transmission and be applicable across related genera of parasites. We have used bioinformatics and transcriptomics to screen for transmission-blocking candidate antigens in the tick-borne apicomplexan parasite,
Theileria annulata
.
Results
A number of candidate antigen genes were identified which encoded amino acid domains that are conserved across vector-borne Apicomplexa (
Babesia
,
Plasmodium
and
Theileria
), including the Pfs48/45 6-cys domain and a novel cysteine-rich domain. Expression profiling confirmed that selected candidate genes are expressed by life cycle stages within infected ticks. Additionally, putative B cell epitopes were identified in the
T. annulata
gene sequences encoding the 6-cys and cysteine rich domains, in a gene encoding a putative papain-family cysteine peptidase, with similarity to the
Plasmodium
SERA family, and the gene encoding the
T. annulata
major merozoite/piroplasm surface antigen,
Tams1
.
Conclusions
Candidate genes were identified that encode proteins with similarity to known transmission blocking candidates in related parasites, while one is a novel candidate conserved across vector-borne apicomplexans and has a potential role in the sexual phase of the life cycle. The results indicate that a ‘One Health’ approach could be utilised to develop a transmission-blocking strategy effective against vector-borne apicomplexan parasites of animals and humans.
Journal Article
Genetic Diversity and Population Structure of Theileria annulata in Oman
Theileriosis, caused by a number of species within the genus Theileria, is a common disease of livestock in Oman. It is a major constraint to the development of the livestock industry due to a high rate of morbidity and mortality in both cattle and sheep. Since little is currently known about the genetic diversity of the parasites causing theileriosis in Oman, the present study was designed to address this issue with specific regard to T. annulata in cattle.
Blood samples were collected from cattle from four geographically distinct regions in Oman for genetic analysis of the Theileria annulata population. Ten genetic markers (micro- and mini-satellites) representing all four chromosomes of T. annulata were applied to these samples using a combination of PCR amplification and fragment analysis. The resultant genetic data was analysed to provide a first insight into the structure of the T. annulata population in Oman.
We applied ten micro- and mini-satellite markers to a total of 310 samples obtained from different regions (174 [56%] from Dhofar, 68 [22%] from Dhira, 44 [14.5%] from Batinah and 24 [8%] from Sharqia). A high degree of allelic diversity was observed among the four parasite populations. Expected heterozygosity for each site ranged from 0.816 to 0.854. A high multiplicity of infection was observed in individual hosts, with an average of 3.3 to 3.4 alleles per locus, in samples derived from Batinah, Dhofar and Sharqia regions. In samples from Dhira region, an average of 2.9 alleles per locus was observed. Mild but statistically significant linkage disequilibrium between pairs of markers was observed in populations from three of the four regions. In contrast, when the analysis was performed at farm level, no significant linkage disequilibrium was observed. Finally, no significant genetic differentiation was seen between the four populations, with most pair-wise FST values being less than 0.03. Slightly higher FST values (GST' = 0.075, θ = 0.07) were detected when the data for T. annulata parasites in Oman was compared with that previously generated for Turkey and Tunisia.
Genetic analyses of T. annulata samples representing four geographical regions in Oman revealed a high level of genetic diversity in the parasite population. There was little evidence of genetic differentiation between parasites from different regions, and a high level of genetic diversity was maintained within each sub-population. These findings are consistent with a high parasite transmission rate and frequent movement of animals between different regions in Oman.
Journal Article
Developing Medical Students’ Broad Clinical Diagnostic Reasoning Through GP-Facilitated Teaching in Hospital Placements
Graduating medical students need broad clinical diagnostic reasoning skills that integrate learning across clinical specialties to deal with undifferentiated patient problems. The opportunity to acquire these skills may be limited during clinical placements on increasingly specialized hospital wards. We developed an intervention of regular general practitioner (GP) facilitated teaching in hospital placements to enable students to develop broad clinical diagnostic reasoning. The intervention was piloted, refined and delivered to a whole cohort of medical students at the start of their third year. This paper examines whether students perceived opportunities to improve their broad diagnostic clinical reasoning through our intervention.
GP-facilitated teaching sessions were delivered weekly in hospital placements to small groups of 6-8 students for 90 mins over 6 weeks. Students practiced clinical reasoning with real patient cases that they encountered on their placements. Evaluation of learning outcomes was conducted through a student questionnaire using Likert scales with free-text boxes for additional explanation. Focus groups were conducted to gain a more in-depth understanding of student perspectives.
As high as 87% of students agreed that their broad clinical diagnostic reasoning ability had improved. Thematic analysis of the qualitative data revealed four factors supporting this improvement: practicing the hypothetico-deductive method, using real patient cases, composing student groups from different speciality placements and the breadth of the facilitators' knowledge. Students additionally reported enhanced person-centredness in terms of understanding the patient's perspective and journey. Students perceived that the added value of general practitioner facilitators lay in their broad knowledge base and knowledge of patient needs in the community.
Our results suggest that medical students can develop broad clinical diagnostic reasoning skills in hospital settings through regular GP-facilitated teaching. Our approach has the advantage of working within the established curricular format of hospital placements and being deliverable at scale to whole student cohorts.
Journal Article
Transformation of the rodent malaria parasite Plasmodium chabaudi
The rodent malaria parasite
Plasmodium chabaudi chabaudi
shares many features with human malaria species, including
P. falciparum
, and is the
in vivo
model of choice for many aspects of malaria research in the mammalian host, from sequestration of parasitized erythrocytes, to antigenic variation and host immunity and immunopathology. This protocol describes an optimized method for the transformation of mature blood-stage
P.c. chabaudi
and a description of a vector that targets efficient, single crossover integration into the
P.c. chabaudi
genome. Transformed lines are reproducibly generated and selected within 14–20 d, and show stable long-term protein expression even in the absence of drug selection. This protocol, therefore, provides the scientific community with a robust and reproducible method to generate transformed
P.c. chabaudi
parasites expressing fluorescent, bioluminescent and model antigens that can be used
in vivo
to dissect many of the fundamental principles of malaria infection.
Journal Article