Focus–specific clinical profiles in human African trypanosomiasis caused by <i>Trypanosoma brucei rhodesiense</i>

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Diverse clinical features have been reported in human African trypanosomiasis (HAT) foci caused by &lt;i&gt;Trypanosoma brucei rhodesiense&lt;/i&gt; (&lt;i&gt;T.b.rhodesiense&lt;/i&gt;) giving rise to the hypothesis that HAT manifests as a chronic disease in South-East African countries and increased in virulence towards the North. Such variation in disease severity suggests there are differences in host susceptibility to trypanosome infection and/or genetic variation in trypanosome virulence. Our molecular tools allow us to study the role of host and parasite genotypes, but obtaining matched extensive clinical data from a large cohort of HAT patients has previously proved problematic.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods/Principal Findings:&lt;/b&gt; We present a retrospective cohort study providing detailed clinical profiles of 275 HAT patients recruited in two northern foci (Uganda) and one southern focus (Malawi) in East Africa. Characteristic clinical signs and symptoms of &lt;i&gt;T.b.rhodesiense&lt;/i&gt; infection were recorded and the degree of neurological dysfunction determined on admission. Clinical observations were mapped by patient estimated post-infection time. We have identified common presenting symptoms in &lt;i&gt;T.b.rhodesiense&lt;/i&gt; infection; however, marked differences in disease progression and severity were identified between foci. HAT was characterised as a chronic haemo-lymphatic stage infection in Malawi, and as an acute disease with marked neurological impairment in Uganda. Within Uganda, a more rapid progression to meningo-encephaltic stage of infection was observed in one focus (Soroti) where HAT was characterised by early onset neurodysfunction; however, severe neuropathology was more frequently observed in patients in a second focus (Tororo).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; We have established focus-specific HAT clinical phenotypes showing dramatic variations in disease severity and rate of stage progression both between northern and southern East African foci and between Ugandan foci. Understanding the contribution of host and parasite factors in causing such clinical diversity in &lt;i&gt;T.b.rhodesiense&lt;/i&gt; HAT has much relevance for both improvement of disease management and the identification of new drug therapy.&lt;/p&gt

Long-term health outcomes after exposure to repeated concussion in elite level: rugby union players

Background: There is continuing concern about effects of concussion in athletes, including risk of the neurodegenerative disease chronic traumatic encephalopathy. However, information on long-term health and wellbeing in former athletes is limited. Method: Outcome after exposure to repeated brain injury was investigated in 52 retired male Scottish international rugby players (RIRP) and 29 male controls who were similar in age and social deprivation. Assessment included history of playing rugby and traumatic brain injury, general and mental health, life stress, concussion symptoms, cognitive function, disability and markers of chronic stress (allostatic load). Results: The estimated number of concussions in RIRP averaged 14 (median=7; IQR 5-40). Performance was poorer in RIRP than controls on a test of verbal learning (p=0.022) and of fine co-ordination of the dominant hand (p=0.038) and not significantly different on other cognitive tests (p&gt;0.05). There were no significant associations between number of concussions and performance on cognitive tests. Other than a higher incidence of cardiovascular disease in controls, no group differences were detected in general or mental health or estimates of allostatic load. In RIRP, persisting symptoms attributed to concussion were more common if reporting more than nine concussions (p=0.028), although these symptoms were not perceived to affect social or work functioning. Conclusions: Despite a high number of concussions in RIRP, differences in mental health, social or work functioning were not found late after injury. Subtle group differences were detected on two cognitive tests, the cause of which is uncertain. Prospective group comparison studies on representative cohorts are required

Using the NANA toolkit at home to predict older adults' future depression

Background: Depression is currently underdiagnosed among older adults. As part of the Novel Assessment of Nu-trition and Aging (NANA) validation study, 40 older adults self-reported their mood using a touchscreen computer over three, one-week periods. Here, we demonstrate the potential of these data to predict future depression status. Methods: We analysed data from the NANA validation study using a machine learning approach. We applied the least absolute shrinkage and selection operator with a logistic model to averages of six measures of mood, with depression status according to the Geriatric Depression Scale 10 weeks later as the outcome variable. We tested multiple values of the selection parameter in order to produce a model with low deviance. We used a cross-validation framework to avoid overspecialisation, and receiver operating characteristic curve (ROC) analysis to determine the quality of the fitted model. Results: The model we report contained coefficients for two variables: sadness and tiredness, as well as a constant. The cross-validated area under the ROC curve for this model was 0.88 (CI: 0.69–0.97). Limitations: While results are based on a small sample, the methodology for the selection of variables appears suitable for the problem at hand, suggesting promise for a wider study and ultimate deployment with older adults at increased risk of depression. Conclusions: We have identified self-reported scales of sadness and tiredness as sensitive measures which have the potential to predict future depression status in older adults, partially addressing the problem of underdiagnosis

Conformal mapping methods for interfacial dynamics

The article provides a pedagogical review aimed at graduate students in materials science, physics, and applied mathematics, focusing on recent developments in the subject. Following a brief summary of concepts from complex analysis, the article begins with an overview of continuous conformal-map dynamics. This includes problems of interfacial motion driven by harmonic fields (such as viscous fingering and void electromigration), bi-harmonic fields (such as viscous sintering and elastic pore evolution), and non-harmonic, conformally invariant fields (such as growth by advection-diffusion and electro-deposition). The second part of the article is devoted to iterated conformal maps for analogous problems in stochastic interfacial dynamics (such as diffusion-limited aggregation, dielectric breakdown, brittle fracture, and advection-diffusion-limited aggregation). The third part notes that all of these models can be extended to curved surfaces by an auxilliary conformal mapping from the complex plane, such as stereographic projection to a sphere. The article concludes with an outlook for further research.Comment: 37 pages, 12 (mostly color) figure

The parent?infant dyad and the construction of the subjective self

Developmental psychology and psychopathology has in the past been more concerned with the quality of self-representation than with the development of the subjective agency which underpins our experience of feeling, thought and action, a key function of mentalisation. This review begins by contrasting a Cartesian view of pre-wired introspective subjectivity with a constructionist model based on the assumption of an innate contingency detector which orients the infant towards aspects of the social world that react congruently and in a specifically cued informative manner that expresses and facilitates the assimilation of cultural knowledge. Research on the neural mechanisms associated with mentalisation and social influences on its development are reviewed. It is suggested that the infant focuses on the attachment figure as a source of reliable information about the world. The construction of the sense of a subjective self is then an aspect of acquiring knowledge about the world through the caregiver's pedagogical communicative displays which in this context focuses on the child's thoughts and feelings. We argue that a number of possible mechanisms, including complementary activation of attachment and mentalisation, the disruptive effect of maltreatment on parent-child communication, the biobehavioural overlap of cues for learning and cues for attachment, may have a role in ensuring that the quality of relationship with the caregiver influences the development of the child's experience of thoughts and feelings

The qualitative transparency deliberations: insights and implications

In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process—the Qualitative Transparency Deliberations (QTD)—involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups’ final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency’s promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports—the full versions of which can be found in the Supplementary Materials—offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate—as understood by relevant research communities—to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript