Assortative mixing as a source of bias in epidemiological studies of sexually transmitted infections: the case of smoking and human papillomavirus

For studies examining risk factors of sexually transmitted infections (STIs), confounding can stem from characteristics of partners of study subjects, and persist after adjustment for the subjects’ individual-level characteristics. Two conditions that can result in confounding by the subjects’ partners are: (C1) partner choice is assortative by the risk factor examined and, (C2) sexual activity is associated with the risk factor. The objective of this paper is to illustrate the potential impact of the assortativity bias in studies examining STI risk factors, using smoking and human papillomavirus (HPV) as an example. We developed an HPV transmission-dynamic mathematical model in which we nested a cross-sectional study assessing the smoking–HPV association. In our base case, we assumed (1) no effect of smoking on HPV, and (2) conditions C1–C2 hold for smoking (based on empirical data). The assortativity bias caused an overestimation of the odds ratio (OR) in the simulated study after perfect adjustment for the subjects’ individual-level characteristics (adjusted OR 1·51 instead of 1·00). The bias was amplified by a lower basic reproductive number (R(0)), greater mixing assortativity and stronger association of smoking with sexual activity. Adjustment for characteristics of partners is needed to mitigate assortativity bias

Animal experimentation in oncology and radiobiology: Arguments for and against following a critical literature review

Despite the international 3Rs principles that recommends replacing, reducing and refining the use of animals in medical experimentation, it remains difficult to obtain funding in Canada for medical research that respects these principles, particularly with regard to replacement. This observation led our team to review the literature on the arguments for and against animal experimentation in the fields of oncology and radiobiology. This article presents a synthesis of these arguments. Using the method created by McCullough and colleagues to conduct critical reviews of the ethics literature, we analysed 25 texts discussing the arguments for and against animal experimentation in oncology and radiobiology. Six broad categories of arguments for animal experimentation and eleven categories of arguments against it emerged from our analyses. Furthermore, the arguments against animal testing are more convincing from both an empirical and normative perspective. Also, most arguments obtained are transferable in other fields of medicine. In addition to the literature review, a critical reflection was conducted and other arguments were discussed. It seems that a conservative culture persists in medical research, despite the scientific evidence and ethical arguments to the contrary. Malgré les principes internationaux des 3R qui recommande de remplacer, réduire et raffiner l’utilisation des animaux dans l’expérimentation médicale, il reste difficile d’obtenir au Canada le financement de recherches médicales qui respectent ces principes, notamment en ce qui concerne le remplacement. Ce constat a amené notre équipe à faire une revue de la littérature sur les arguments pour et contre l’expérimentation animale dans les domaines de l’oncologie et de la radiobiologie. Cet article présente une synthèse de ces arguments. En utilisant la méthode créée par McCullough et collègues pour réaliser des revues critiques de la littérature en éthique, nous avons analysé 25 écrits discutant des arguments pour et contre l’expérimentation animale en oncologie et en radiobiologie. Six grandes catégories d’arguments en faveur de l’expérimentation animale et onze catégories d’arguments contre celle-ci sont ressorties de nos analyses. En outre, les arguments contre l’expérimentation animale sont plus convaincants d’un point de vue empirique et normatif. De plus, la plupart des arguments obtenus sont transférables dans d’autres domaines de la médecine. En plus de l’analyse documentaire, une réflexion critique a été menée et d’autres arguments ont été discutés. Il semble qu’une culture conservatrice persiste dans la recherche médicale, malgré les preuves scientifiques et les arguments éthiques contraires

Potential population-level effectiveness of one-dose HPV vaccination in low-income and middle-income countries: a mathematical modelling analysis

BACKGROUND: Given the accumulating evidence that one-dose vaccination could provide high and sustained protection against human papillomavirus (HPV) infection and related diseases, we examined the population-level effectiveness and efficiency of one-dose HPV vaccination of girls compared with two-dose vaccination, using mathematical modelling. METHODS: In this mathematical modelling study, we used HPV-ADVISE LMIC, an individual-based transmission-dynamic model independently calibrated to four epidemiologically diverse low-income and middle-income countries (LMICs; India, Nigeria, Uganda, and Viet Nam). We parameterised and calibrated the model using sexual behaviour and epidemiological data identified from international population-based datasets and the literature. All base-case vaccination scenarios start in 2023 with the nonavalent vaccine and assumed 80% vaccination coverage with one or two doses. We assumed that two doses of vaccine provide 100% efficacy against vaccine-type infections and a lifelong duration of protection. We examined a non-inferior vaccination scenario for one dose compared with two doses, pessimistic scenarios of lower one-dose vaccine efficacy (85%) or a shorter duration of protection (ie, 20 or 30 years), and the effectiveness of a mitigation scenario in which schedules would switch from one dose to two doses. We also did sensitivity analyses by varying vaccination coverage. We used three outcomes: the relative reduction in cervical cancer incidence, the number of cervical cancers averted, and the number of vaccine doses needed to prevent one cervical cancer. FINDINGS: Assuming non-inferior vaccine characteristics for one dose compared with two doses, the model projections show that two-dose or one-dose routine vaccination of girls aged 9 years (with a multi-age cohort vaccination of girls aged 10-14 years) would avert 12·0 million (80% UI 9·5-14·5) cervical cancers in India, 4·7 million (3·4-5·8) in Nigeria, 2·3 million (1·9-2·6) in Uganda, and 0·4 million (0·2-0·5) in Viet Nam over 100 years. Under pessimistic assumptions of lower one-dose efficacy (85%) or a shorter duration of protection (ie, 30 years), one-dose routine vaccination would avert 69% (61-80) to 94% (92-96) of the cervical cancers averted with two-dose routine vaccination. However, when assuming a duration of protection of 20 years, one-dose routine vaccination would avert substantially fewer cervical cancers (ie, 35% [26-44] to 69% [65-71] of the cervical cancers averted with two-dose routine vaccination). A switch from one-dose to two-dose routine vaccination of girls aged 9 years, with a one-dose catch-up of girls aged 10-14 years, 5 years after the start of the vaccination programme, could mitigate potential losses in cervical cancer prevention from a short one-dose duration of protection (averting 92% [83-98] to 99% [97-100]) of the cervical cancers averted with two-dose routine vaccination). One-dose routine vaccination would result in fewer doses needed to prevent one cervical cancer than two-dose routine vaccination, even if the duration of protection is as low as 20 years. Finally, for countries with two-dose routine vaccination, adding one-dose multi-age cohort vaccination in the first year would provide similar benefits as a two-dose multi-age cohort vaccination, and would be more efficient even under the pessimistic assumptions of lower one-dose vaccine efficacy or duration of protection. INTERPRETATION: One-dose routine vaccination could avert most of the cervical cancers averted with two-dose vaccination while being more efficient, provided the duration of one-dose protection is greater than 20-30 years (depending on the LMIC). The doses saved by introducing one-dose routine vaccination could offer the opportunity to vaccinate girls before they age out of the vaccination window of 9-14 years and, potentially, to vaccinate boys or older age groups. FUNDING: Fonds de recherche du Québec-Santé, Digital Research Alliance of Canada, Bill & Melinda Gates Foundation

Neurodevelopmental abnormalities in children with PHACE syndrome.

Prior case reports have identified neurodevelopmental abnormalities in children with PHACE syndrome, a neurocutaneous disorder first characterized in 1996. In this multicenter, retrospective study of a previously identified cohort of 93 children diagnosed with PHACE syndrome from 1999 to 2010, 29 children had neurologic evaluations at ≥ 1 year of age (median age: 4 years, 2 months). In all, 44% had language delay, 36% gross motor delay, and 8% fine motor delay; 52% had an abnormal neurological exam, with speech abnormalities as the most common finding. Overall, 20 of 29 (69%) had neurodevelopmental abnormalities. Cerebral, but not posterior fossa, structural abnormalities were identified more often in children with abnormal versus normal neurodevelopmental outcomes (35% vs. 0%, P = .04). Neurodevelopmental abnormalities in young children with PHACE syndrome referred to neurologists include language and gross motor delay, while fine motor delay is less frequent. Prospective studies are needed to understand long-term neurodevelopmental outcomes

Conceptualising ethical issues in the conduct of research: Results from a critical and systematic literature review

This article concerns  the ways in which authors from various fields conceptualise the ethical issues arising in the conduct of research. We reviewed critically and systematically the literature concerning the ethics of conducting research in order to engage in a reflection about the vocabulary and conceptual categories used in the publications reviewed. To understand better how the ethical issues involved in conducting research are conceptualised in the publications reviewed, we 1) established an inventory of the conceptualisations reviewed, and 2) we critically assessed them. We found that the publications reviewed mostly showed examples of descriptive ethics, in that most authors describe ethical issues without reflecting much on them, which could be explained both by 1) a lack of ethical education in research contexts, and 2) by the fact that we do not know what researchers know (or do not) about ethical issues. Additionally, the definitions identified in the publications are scarce and at times imprecise, but this seems more to point out the ethical vocabulary’s difficulties in certain contexts. Further, very few authors offer proper conceptualisations of the ethical issues arising in conducting research. When dealing with vast arrays of ethical issues to conceptualise, perhaps one ought to remember that some typologies already exist that could guide further reflection and help understand other realities for which the current ethical vocabulary may be lacking. We believe that combining the reviewed typologies, both with other well-developed typologies and critical reflection, could help support better ethical practice in conducting research

Grain boundary pinning and glassy dynamics in stripe phases

We study numerically and analytically the coarsening of stripe phases in two spatial dimensions, and show that transient configurations do not achieve long ranged orientational order but rather evolve into glassy configurations with very slow dynamics. In the absence of thermal fluctuations, defects such as grain boundaries become pinned in an effective periodic potential that is induced by the underlying periodicity of the stripe pattern itself. Pinning arises without quenched disorder from the non-adiabatic coupling between the slowly varying envelope of the order parameter around a defect, and its fast variation over the stripe wavelength. The characteristic size of ordered domains asymptotes to a finite value $R_g \sim \lambda_0\ \epsilon^{-1/2}\exp(|a|/\sqrt{\epsilon})$, where$\epsilon\ll 1$is the dimensionless distance away from threshold,$\lambda_0$the stripe wavelength, and$a$ a constant of order unity. Random fluctuations allow defect motion to resume until a new characteristic scale is reached, function of the intensity of the fluctuations. We finally discuss the relationship between defect pinning and the coarsening laws obtained in the intermediate time regime.Comment: 17 pages, 8 figures. Corrected version with one new figur

Phase diagram for diblock copolymer melts under cylindrical confinement

We extensively study the phase diagram of a diblock copolymer melt confined in a cylindrical nanopore using real-space self-consistent mean-field theory. We discover a rich variety of new two-dimensional equilibrium structures that have no analog in the unconfined system. These include non-hexagonally coordinated cylinder phases and structures intermediate between lamellae and cylinders. We map the stability regions and phase boundaries for all the structures we find. As the pore radius is decreased, the pore accommodates fewer cylindrical domains and structural transitions occur as cylinders are eliminated. Our results are consistent with experiments, but we also predict phases yet to be observed.Comment: 12 pages, 3 figures. submitted to Physical Review Letter

Laugh Like You Mean It:Authenticity Modulates Acoustic, Physiological and Perceptual Properties of Laughter

Several authors have recently presented evidence for perceptual and neural distinctions between genuine and acted expressions of emotion. Here, we describe how differences in authenticity affect the acoustic and perceptual properties of laughter. In an acoustic analysis, we contrasted spontaneous, authentic laughter with volitional, fake laughter, finding that spontaneous laughter was higher in pitch, longer in duration, and had different spectral characteristics from volitional laughter that was produced under full voluntary control. In a behavioral experiment, listeners perceived spontaneous and volitional laughter as distinct in arousal, valence, and authenticity. Multiple regression analyses further revealed that acoustic measures could significantly predict these affective and authenticity judgements, with the notable exception of authenticity ratings for spontaneous laughter. The combination of acoustic predictors differed according to the laughter type, where volitional laughter ratings were uniquely predicted by harmonics-to-noise ratio (HNR). To better understand the role of HNR in terms of the physiological effects on vocal tract configuration as a function of authenticity during laughter production, we ran an additional experiment in which phonetically trained listeners rated each laugh for breathiness, nasality, and mouth opening. Volitional laughter was found to be significantly more nasal than spontaneous laughter, and the item-wise physiological ratings also significantly predicted affective judgements obtained in the first experiment. Our findings suggest that as an alternative to traditional acoustic measures, ratings of phonatory and articulatory features can be useful descriptors of the acoustic qualities of nonverbal emotional vocalizations, and of their perceptual implications

Sharp interface limits of phase-field models

The use of continuum phase-field models to describe the motion of well-defined interfaces is discussed for a class of phenomena, that includes order/disorder transitions, spinodal decomposition and Ostwald ripening, dendritic growth, and the solidification of eutectic alloys. The projection operator method is used to extract the ``sharp interface limit'' from phase field models which have interfaces that are diffuse on a length scale $\xi$. In particular,phase-field equations are mapped onto sharp interface equations in the limits $\xi \kappa \ll 1$ and $\xi v/D \ll 1$, where $\kappa$ and $v$ are respectively the interface curvature and velocity and $D$ is the diffusion constant in the bulk. The calculations provide one general set of sharp interface equations that incorporate the Gibbs-Thomson condition, the Allen-Cahn equation and the Kardar-Parisi-Zhang equation.Comment: 17 pages, 9 figure