Kinematics and Hydrodynamics of Undulatory Locomotion in Hagfishes (Myxinidae) and Hagfish-like Robotic Models

Hagfishes have both intrigued and confused biologists since Linnaeus first mistakenly classified one as an "intestinal worm." Modern hagfishes (Myxinidae) are elongate, marine fishes often described by what they lack: jaws, scales, paired fins, or a vertebral column. Accompanying this reduced morphology was a long-held view that hagfish are lazy animals that mostly lay about on the ocean floor, but more recent research has revealed them to be active hunters and scavengers in the benthic community. Routine swimming is a requisite part of these activities, yet knowledge of how these exceptionally flexible fishes swim is limited. Here, I use an integrative experimental approach to provide a more comprehensive, quantitative understanding of locomotory mechanisms in hagfishes. In Chapters 1 and 2, I use high-speed videography to quantify whole-body kinematics of steady and unsteady swimming in Eptatretus stoutii and Myxine glutinosa, representing the two main lineages within Myxinidae. Both species generally swim with high amplitude head movements and use tail beat frequency to control swim speed, but inter- and intra-specific variation in other undulatory wave variables suggests multiple mechanisms to modulate speed. Changes in the shape of the body wave characterize the observed unsteady swimming behaviors. During positive linear accelerations, hagfish transiently adopt a larger, longer body wave. During lateral maneuvers, hagfish approximate “sidewinding” behavior as anterior body regions interact with the substrate while posterior body regions propagate waves of lateral bending toward the tail tip. Chapter 3 integrates kinematics with hydrodynamics, using particle image velocimetry to visualize the flow field around swimming E. stoutii. The steady swimming wake consists of caudolateral fluid jets, which turn caudally during linear accelerations. Wake jets orient asymmetrically during lateral swimming, contributing both forward and lateral thrust over a complete tail beat. The hydrodynamic patterns observed reinforce kinematics-based hypotheses on how hagfishes enact their various swimming behaviors. In Chapter 4, I use simple robotically-controlled physical models to examine functional relationships between body flexural stiffness, shape, kinematics, hydrodynamics, and swimming performance. I relate model swim performance to characteristics of hagfish swimming, and describe lessons that passively undulating models impart for understanding locomotion by live elongate undulatory swimmers

"I think it is right": a qualitative exploration of the acceptability and desired future use of oral swab and finger-prick HIV self-tests by lay users in KwaZulu-Natal, South Africa.

The uptake of HIV testing has increased in sub-Saharan Africa over the past three decades. However, the proportion of people aware of their HIV status remains lower than required to change the pandemic. HIV self-testing (HIVST) may meet this gap. Assessment of readiness for and the acceptability of HIVST by lay users in South Africa is limited. This paper presents results from a formative study designed to assess the perceived usability and acceptability of HIVST among lay users using several self-test prototypes. Fifty lay users were purposively selected from rural and peri-urban KwaZulu-Natal, South Africa. Acceptability of HIVST was assessed using a simple post-test quantitative assessment tool addressing confidence, ease-of-use, intended future use and willingness to pay. In-depth qualitative interviews explored what participants felt about the HIVST and why, their willingness to recommend and how much they would pay for a test. The key finding is that there is high acceptability regardless of self-test prototype. Acceptability is framed by two domains: usability and perceived need. Perceived usability was explored through perceived ease of use, which, regardless of actual correct usage, was reported by many of the respondents. Acceptability is influenced by perceived need, expressed by many who felt that the need for the self-test to protect privacy and autonomy. Ease of access and widespread availability of the test, not at a significant cost, were also important factors. Many participants would recommend self-test use to others and also indicated that they would choose to conduct the test again if it was free while some also indicated being willing to buy a test. The positive response and readiness amongst lay users for an HIVST in this context prototype suggests that there would be a ready and willing market for HIVST. For scalability and sustainability usability, including access and availability that are here independent indications of acceptability, should be considered. So too should the desire for future use, as an additional factor pointing to acceptability. The results show high acceptability in all of these areas domains and a general interest in HIVST amongst lay users in a community in KwaZulu-Natal

Acceptability of self-collection sampling for HPV-DNA testing in low-resource settings: a mixed methods approach.

BACKGROUND: Vaginal self-sampling with HPV-DNA tests is a promising primary screening method for cervical cancer. However, women's experiences, concerns and the acceptability of such tests in low-resource settings remain unknown. METHODS: In India, Nicaragua, and Uganda, a mixed-method design was used to collect data from surveys (N = 3,863), qualitative interviews (N = 72; 20 providers and 52 women) and focus groups (N = 30 women) on women's and providers' experiences with self-sampling, women's opinions of sampling at home, and their future needs. RESULTS: Among surveyed women, 90% provided a self- collected sample. Of these, 75% reported it was easy, although 52% were initially concerned about hurting themselves and 24% were worried about not getting a good sample. Most surveyed women preferred self-sampling (78%). However it was not clear if they responded to the privacy of self-sampling or the convenience of avoiding a pelvic examination, or both. In follow-up interviews, most women reported that they didn't mind self-sampling, but many preferred to have a provider collect the vaginal sample. Most women also preferred clinic-based screening (as opposed to home-based self-sampling), because the sample could be collected by a provider, women could receive treatment if needed, and the clinic was sanitary and provided privacy. Self-sampling acceptability was higher when providers prepared women through education, allowed women to examine the collection brush, and were present during the self-collection process. Among survey respondents, aids that would facilitate self-sampling in the future were: staff help (53%), additional images in the illustrated instructions (31%), and a chance to practice beforehand with a doll/model (26%). CONCLUSION: Self-and vaginal-sampling are widely acceptable among women in low-resource settings. Providers have a unique opportunity to educate and prepare women for self-sampling and be flexible in accommodating women's preference for self-sampling

Evaluating empowerment in genetic counseling using patient-reported outcomes

Data about patient reported outcomes from cancer genetics services (CGS) are lacking but are essential to guide service evaluation and improvements. We measured improvement in empowerment, following genetic counseling in Singapore using a culturally‐adapted version of the Genetic Counseling Outcome Scale (GCOS‐24); and sought to identify factors associated with change in empowerment. The GCOS‐24 was administered to 155 patients of the CGS, at pre‐ and post‐counseling or testing timepoints. Of which, 110 patients underwent genetic testing. Individual pre‐ and post‐counseling responses were subjected to Rasch analysis; the scale was subsequently split into cognitive control (CC) and emotional control (EC) domains. Associations of baseline characteristics with changes in pre‐ and post‐CC and EC scores were assessed using multiple regression analysis. Both CC and EC scores showed significant improvement following genetic counseling and testing. While all items in the CC domain of being showed increases at follow‐up, aspects of EC related to alleviating negative emotions (P = .88) and hopelessness (P = .2) did not show significant improvement. Our study revealed significant improvement in empowerment in patients who have received cancer genetic counseling, while revealing a need to cultivate hope and facilitate the alleviation of negative emotions in patients during genetic counseling

Challenges Associated with Estimating Utility in Wet Age-Related Macular Degeneration : A Novel Regression Analysis to Capture the Bilateral Nature of the Disease

INTRODUCTION: The estimation of utility values for the economic evaluation of therapies for wet age-related macular degeneration (AMD) is a particular challenge. Previous economic models in wet AMD have been criticized for failing to capture the bilateral nature of wet AMD by modelling visual acuity (VA) and utility values associated with the better-seeing eye only. METHODS: Here we present a de novo regression analysis using generalized estimating equations (GEE) applied to a previous dataset of time trade-off (TTO)-derived utility values from a sample of the UK population that wore contact lenses to simulate visual deterioration in wet AMD. This analysis allows utility values to be estimated as a function of VA in both the better-seeing eye (BSE) and worse-seeing eye (WSE). RESULTS: VAs in both the BSE and WSE were found to be statistically significant (p < 0.05) when regressed separately. When included without an interaction term, only the coefficient for VA in the BSE was significant (p = 0.04), but when an interaction term between VA in the BSE and WSE was included, only the constant term (mean TTO utility value) was significant, potentially a result of the collinearity between the VA of the two eyes. The lack of both formal model fit statistics from the GEE approach and theoretical knowledge to support the superiority of one model over another make it difficult to select the best model. CONCLUSION: Limitations of this analysis arise from the potential influence of collinearity between the VA of both eyes, and the use of contact lenses to reflect VA states to obtain the original dataset. Whilst further research is required to elicit more accurate utility values for wet AMD, this novel regression analysis provides a possible source of utility values to allow future economic models to capture the quality of life impact of changes in VA in both eyes. FUNDING: Novartis Pharmaceuticals UK Limited

Long-term exposure to air pollution and stroke incidence:A Danish Nurse cohort study

Ambient air pollution has been linked to stroke, but few studies have examined in detail stroke subtypes and confounding by road traffic noise, which was recently associated with stroke. Here we examined the association between long-term exposure to air pollution and incidence of stroke (overall, ischemic, hemorrhagic), adjusting for road traffic noise. In a nationwide Danish Nurse Cohort consisting of 23,423 nurses, recruited in 1993 or 1999, we identified 1,078 incident cases of stroke (944 ischemic and 134 hemorrhagic) up to December 31, 2014, defined as first-ever hospital contact. The full residential address histories since 1970 were obtained for each participant and the annual means of air pollutants (particulate matter with diameter < 2.5 μm and < 10 μm (PM2.5 and PM10), nitrogen dioxide (NO2), nitrogen oxides (NOx)) and road traffic noise were determined using validated models. Time-varying Cox regression models were used to estimate hazard ratios (HR) (95% confidence intervals (CI)) for the associations of one-, three, and 23-year running mean of air pollutants with stroke adjusting for potential confounders and noise. In fully adjusted models, the HRs (95% CI) per interquartile range increase in one-year running mean of PM2.5 and overall, ischemic, and hemorrhagic stroke were 1.12 (1.01–1.25), 1.13 (1.01–1.26), and 1.07 (0.80–1.44), respectively, and remained unchanged after adjustment for noise. Long-term exposure to ambient PM2.5 was associated with the risk of stroke independent of road traffic noise

A multicountry evaluation of careHPV testing, visual inspection with acetic acid, and papanicolaou testing for the detection of cervical cancer.

OBJECTIVE: This study evaluates the feasibility and performance of careHPV, a novel human papillomavirus (HPV) DNA test, when used for screening women for cervical cancer in low-resource settings. METHODS AND MATERIALS: Clinician-collected (cervical) and self-collected (vaginal) careHPV specimens, visual inspection with acetic acid (VIA), and Papanicolaou test were evaluated among 16,951 eligible women in India, Nicaragua, and Uganda. Women with positive screening results received colposcopy and histologic follow-up as indicated. The positivity of each screening method was calculated overall, by site, and age. In addition, the clinical performance of each screening test was determined for detection of cervical intraepithelial neoplasia (CIN) grade 2 (CIN2+) and CIN grade 3. RESULTS: Moderate or severe dysplasia or cancer (taken together as CIN2+) was diagnosed in 286 women. The positivity rate ranged between 2.4% to 19.6% for vaginal careHPV, 2.9% to 20.2% for cervical careHPV, 5.5% to 34.4% for VIA, and 2.8% to 51.8% for Papanicolaou test. Cervical careHPV was the most sensitive for CIN2+ (81.5%; 95% confidence interval [CI], 76.5-85.8) and CIN grade 3 (85.3%; 95% CI, 78.6-90.6) at all sites, followed by vaginal careHPV (69.6% and 71.3%, respectively). The sensitivity of VIA ranged from 21.9% to 73.6% and Papanicolaou test from 40.7% to 73.7%. The pooled specificities of cervical careHPV, vaginal careHPV, VIA, and Papanicolaou test were 91.6%, 90.6%, 84.2%, and 87.7%, respectively. CONCLUSIONS: careHPV performed well in large multicountry demonstration studies conducted in resource-limited settings that have not previously been conducted this type of testing; its sensitivity using cervical samples or vaginal self-collected samples was better than VIA or Papanicolaou test. The feasibility of using careHPV in self-collected vaginal samples opens the possibility of increasing coverage and early detection in resource-constrained areas

Trait impulsivity in Juvenile Myoclonic Epilepsy

Impulsivity is a multidimensional construct that can predispose to psychopathology. Meta‐analysis demonstrates an association between response impulsivity and Juvenile Myoclonic Epilepsy (JME), a common genetic generalized epilepsy. Here, we test the hypotheses that trait impulsivity is (i) elevated in JME compared to controls; (ii) moderated by specific seizure characteristics; and (iii) associated with psychiatric adverse effects of antiepileptic drugs (AEDs)

Long-term exposure to transportation noise and risk of incident stroke:A pooled study of nine scandinavian cohorts

BACKGROUND: Transportation noise is increasingly acknowledged as a cardiovascular risk factor, but the evidence base for an association with stroke is sparse. OBJECTIVE: We aimed to investigate the association between transportation noise and stroke incidence in a large Scandinavian population. METHODS: We harmonized and pooled data from nine Scandinavian cohorts (seven Swedish, two Danish), totaling 135,951 participants. We identified residential address history and estimated road, railway, and aircraft noise for all addresses. Information on stroke incidence was acquired through link-age to national patient and mortality registries. We analyzed data using Cox proportional hazards models, including socioeconomic and lifestyle con-founders, and air pollution. RESULTS: During follow-up (median = 19:5 y), 11,056 stroke cases were identified. Road traffic noise (Lden ) was associated with risk of stroke, with a hazard ratio (HR) of 1.06 [95% confidence interval (CI): 1.03, 1.08] per 10-dB higher 5-y mean time-weighted exposure in analyses adjusted for indi-vidual-and area-level socioeconomic covariates. The association was approximately linear and persisted after adjustment for air pollution [particulate matter (PM) with an aerodynamic diameter of ≤2:5 lm (PM2:5 ) and NO2 ]. Stroke was associated with moderate levels of 5-y aircraft noise exposure (40–50 vs. ≤40 dB) (HR = 1:12; 95% CI: 0.99, 1.27), but not with higher exposure (≥50 dB, HR = 0:94; 95% CI: 0.79, 1.11). Railway noise was not associated with stroke. DISCUSSION: In this pooled study, road traffic noise was associated with a higher risk of stroke. This finding supports road traffic noise as an important cardiovascular risk factor that should be included when estimating the burden of disease due to traffic noise. https://doi.org/10.1289/EHP8949