A semi-Markov model for stroke with piecewise-constant hazards in the presence of left, right and interval censoring.

This paper presents a parametric method of fitting semi-Markov models with piecewise-constant hazards in the presence of left, right and interval censoring. We investigate transition intensities in a three-state illness-death model with no recovery. We relax the Markov assumption by adjusting the intensity for the transition from state 2 (illness) to state 3 (death) for the time spent in state 2 through a time-varying covariate. This involves the exact time of the transition from state 1 (healthy) to state 2. When the data are subject to left or interval censoring, this time is unknown. In the estimation of the likelihood, we take into account interval censoring by integrating out all possible times for the transition from state 1 to state 2. For left censoring, we use an Expectation-Maximisation inspired algorithm. A simulation study reflects the performance of the method. The proposed combination of statistical procedures provides great flexibility. We illustrate the method in an application by using data on stroke onset for the older population from the UK Medical Research Council Cognitive Function and Ageing Study

Medical Help-Seeking for Sexual Concerns in Prostate Cancer Survivors.

INTRODUCTION: Although sexual dysfunction is common after prostate cancer, men's decisions to seek help for sexual concerns are not well understood. AIM: Describe predictors of actual prior help-seeking and intended future medical help-seeking for sexual dysfunction in prostate cancer survivors. METHODS: A cross-sectional survey of 510 prostate cancer survivors assessed masculine beliefs, attitudes, support/approval from partner/peer networks (subjective norm), and perceived control as predictors of medical help-seeking for sexual concerns. A theory of planned behavior (TPB) perspective was used to examine actual prior and planned future behavior and contributing factors. Statistical analyses included multiple and logistic regressions. MAIN OUTCOME MEASURES: Intention to see a doctor for sexual advice or help in the next 6 months was measured using the intention subscale adapted from the Attitudes to Seeking Help after Cancer Scale. Prior help-seeking was measured with a dichotomous yes/no scale created for the study. RESULTS: Men were Mage 71.69 years (SD = 7.71); 7.54 years (SD = 4.68) post-diagnosis; received treatment(s) (58.1% radical prostatectomy; 47.1% radiation therapy; 29.4% hormonal ablation); 81.4% reported severe ED (IIED 0-6) and 18.6% moderate-mild ED (IIED 7-24). Overall, 30% had sought sexual help in the past 6 months, and 24% intended to seek help in the following 6 months. Prior help-seeking was less frequent among men with severe ED. Sexual help-seeking intentions were associated with lower education, prior sexual help-seeking, sexual importance/ priority, emotional self-reliance, positive attitude, and subjective norm (R(2) = 0.56). CONCLUSION: The TPB has utility as a theoretical framework to understand prostate cancer survivors' sexual help-seeking decisions and may inform development of more effective interventions. Masculine beliefs were highly salient. Men who were more emotionally self-reliant and attributed greater importance to sex formed stronger help-seeking intentions. Subjective norm contributed most strongly to help-seeking intentions suggesting that health professionals/partners/peers have a key role as support mechanisms and components of psycho-sexual interventions

Active Tension Network model suggests an exotic mechanical state realized in epithelial tissues.

Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behavior remains an open problem. Here we formulate and analyze the Active Tension Network (ATN) model, which assumes that the mechanical balance of cells within a tissue is dominated by cortical tension and introduces tension-dependent active remodeling of the cortex. We find that ATNs exhibit unusual mechanical properties. Specifically, an ATN behaves as a fluid at short times, but at long times supports external tension like a solid. Furthermore, an ATN has an extensively degenerate equilibrium mechanical state associated with a discrete conformal - "isogonal" - deformation of cells. The ATN model predicts a constraint on equilibrium cell geometries, which we demonstrate to approximately hold in certain epithelial tissues. We further show that isogonal modes are observed in the fruit y embryo, accounting for the striking variability of apical areas of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, the study of which helps to understand biological phenomena

Cosmic strings from pseudo-anomalous Fayet-Iliopoulos U(1) in D3/D7 brane inflation

We examine the consequences of recent developments on Fayet-Iliopoulos (FI) terms for D-term inflationary models. There is currently no known way to couple constant FI terms to supergravity consistently; only field-dependent FI terms are allowed. These are natural in string theory and we argue that the FI term in D3/D7 inflation turns out to be of this type, corresponding to a pseudo-anomalous U(1). T he anomaly is canceled by the Green-Schwarz mechanism in 4 dimensions. Inflation proceeds as usual, except that the scale is set by the GS parameter. Cosmic strings resulting from a pseudo-anomalous U(1) have potentially interesting characteristics. Originally expected to be global, they turn out to be local in the string theory context and can support currents. We outline the nature of these strings, discuss bounds on their formation, and summarize resulting cosmological consequences.Comment: 10 pages; minor changes to match published versio

Identifying and addressing conflicting results across multiple discordant systematic reviews on the same question: protocol for a replication study of the Jadad algorithm

Introduction An increasing growth of systematic reviews (SRs) presents notable challenges for decision-makers seeking to answer clinical questions. In 1997, an algorithm was created by Jadad to assess discordance in results across SRs on the same question. Our study aims to (1) replicate assessments done in a sample of studies using the Jadad algorithm to determine if the same SR would have been chosen, (2) evaluate the Jadad algorithm in terms of utility, efficiency and comprehensiveness, and (3) describe how authors address discordance in results across multiple SRs. Methods and analysis We will use a database of 1218 overviews (2000-2020) created from a bibliometric study as the basis of our search for studies assessing discordance (called discordant reviews). This bibliometric study searched MEDLINE (Ovid), Epistemonikos and Cochrane Database of Systematic Reviews for overviews. We will include any study using Jadad (1997) or another method to assess discordance. The first 30 studies screened at the full-text stage by two independent reviewers will be included. We will replicate the authors' Jadad assessments. We will compare our outcomes qualitatively and evaluate the differences between our Jadad assessment of discordance and the authors' assessment. Ethics and dissemination No ethics approval was required as no human subjects were involved. In addition to publishing in an open-access journal, we will disseminate evidence summaries through formal and informal conferences, academic websites, and across social media platforms. This is the first study to comprehensively evaluate and replicate Jadad algorithm assessments of discordance across multiple SRs

Branch Mode Selection during Early Lung Development

Many organs of higher organisms, such as the vascular system, lung, kidney, pancreas, liver and glands, are heavily branched structures. The branching process during lung development has been studied in great detail and is remarkably stereotyped. The branched tree is generated by the sequential, non-random use of three geometrically simple modes of branching (domain branching, planar and orthogonal bifurcation). While many regulatory components and local interactions have been defined an integrated understanding of the regulatory network that controls the branching process is lacking. We have developed a deterministic, spatio-temporal differential-equation based model of the core signaling network that governs lung branching morphogenesis. The model focuses on the two key signaling factors that have been identified in experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well as the SHH receptor patched (Ptc). We show that the reported biochemical interactions give rise to a Schnakenberg-type Turing patterning mechanisms that allows us to reproduce experimental observations in wildtype and mutant mice. The kinetic parameters as well as the domain shape are based on experimental data where available. The developed model is robust to small absolute and large relative changes in the parameter values. At the same time there is a strong regulatory potential in that the switching between branching modes can be achieved by targeted changes in the parameter values. We note that the sequence of different branching events may also be the result of different growth speeds: fast growth triggers lateral branching while slow growth favours bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is sufficient to generate pattern that correspond to the observed branching modesComment: Initially published at PLoS Comput Bio

Active Electric Imaging: Body-Object Interplay and Object's “Electric Texture”

This article deals with the role of fish's body and object's geometry on determining the image spatial shape in pulse Gymnotiforms. This problem was explored by measuring local electric fields along a line on the skin in the presence and absence of objects. We depicted object's electric images at different regions of the electrosensory mosaic, paying particular attention to the perioral region where a fovea has been described. When sensory surface curvature increases relative to the object's curvature, the image details depending on object's shape are blurred and finally disappear. The remaining effect of the object on the stimulus profile depends on the strength of its global polarization. This depends on the length of the object's axis aligned with the field, in turn depending on fish body geometry. Thus, fish's body and self-generated electric field geometries are embodied in this “global effect” of the object. The presence of edges or local changes in impedance at the nearest surface of closely located objects adds peaks to the image profiles (“local effect” or “object's electric texture”). It is concluded that two cues for object recognition may be used by active electroreceptive animals: global effects (informing on object's dimension along the field lines, conductance, and position) and local effects (informing on object's surface). Since the field has fish's centered coordinates, and electrosensory fovea is used for exploration of surfaces, fish fine movements are essential to perform electric perception. We conclude that fish may explore adjacent objects combining active movements and electrogenesis to represent them using electrosensory information

Anti-müllerian hormone is not associated with cardiometabolic risk factors in adolescent females

<p>Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.</p> <p>Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes.</p> <p>Results: AMH values ranged from 0.16–35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ml (2.23, 5.05) in those classed as early pubertal (n = 460, P≤0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: −3%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives.</p> <p>Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.</p&gt

Regulation of sensory nerve conduction velocity (SCV) of human bodies responding to annual temperature variations in natural environments

The extensive research interests in environmental temperature can be linked to human productivity/performance as well as comfort and health; while the mechanisms of physiological indices responding to temperature variations remain incompletely understood. This study adopted a physiological sensory nerve conduction velocity (SCV) as a temperature-sensitive biomarker to explore the thermoregulatory mechanisms of human responding to annual temperatures. The measurements of subjects’ SCV (over 600 samples) were conducted in a naturally ventilated environment over all four seasons. The results showed a positive correlation between SCV and annual temperatures and a Boltzmann model was adopted to depict the S-shaped trend of SCV with operative temperatures from 5 °C to 40 °C. The SCV increased linearly with operative temperatures from 14.28 °C to 20.5 °C and responded sensitively for 10.19 °C - 24.59 °C, while tended to be stable beyond that. The subjects’ thermal sensations were linearly related to SCV, elaborating the relation between human physiological regulations and subjective thermal perception variations. The findings reveal the body SCV regulatory characteristics in different operative temperature intervals, thereby giving a deeper insight into human autonomic thermoregulation and benefiting for built environment designs, meantime minimizing the temperature-invoked risks to human health and well-being