Impact of physiological noise correction on detecting blood oxygenation level-dependent contrast in the breast.

Physiological fluctuations are expected to be a dominant source of noise in blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) experiments to assess tumour oxygenation and angiogenesis. This work investigates the impact of various physiological noise regressors: retrospective image correction (RETROICOR), heart rate (HR) and respiratory volume per unit time (RVT), on signal variance and the detection of BOLD contrast in the breast in response to a modulated respiratory stimulus. BOLD MRI was performed at 3 T in ten volunteers at rest and during cycles of oxygen and carbogen gas breathing. RETROICOR was optimized using F-tests to determine which cardiac and respiratory phase terms accounted for a significant amount of signal variance. A nested regression analysis was performed to assess the effect of RETROICOR, HR and RVT on the model fit residuals, temporal signal-to-noise ratio, and BOLD activation parameters. The optimized RETROICOR model accounted for the largest amount of signal variance ([Formula: see text]  =  3.3  ±  2.1%) and improved the detection of BOLD activation (P  =  0.002). Inclusion of HR and RVT regressors explained additional signal variance, but had a negative impact on activation parameter estimation (P  <  0.001). Fluctuations in HR and RVT appeared to be correlated with the stimulus and may contribute to apparent BOLD signal reactivity.This work was supported by the NIHR Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre and the CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester (C197/A16465 and C8742/A18097)

Coronavirus Disease 2019 (COVID-19) Transmission in the United States Before Versus After Relaxation of Statewide Social Distancing Measures

BACKGROUND: Weeks after issuing social distancing orders to suppress severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and reduce growth in cases of severe coronavirus disease 2019 (COVID-19), all U.S. states and the District of Columbia partially or fully relaxed these measures. METHODS: We identified all statewide social distancing measures that were implemented and/or relaxed in the U.S. between March 10-July 15, 2020, triangulating data from state government and third-party sources. Using segmented linear regression, we estimated the extent to which relaxation of social distancing affected epidemic control, as indicated by the time-varying, state-specific effective reproduction number (Rt). RESULTS: In the eight weeks prior to relaxation, mean Rt declined by 0.012 units per day (95% CI, -0.013 to -0.012), and 46/51 jurisdictions achieved Rt < 1.0 by the date of relaxation. After relaxation of social distancing, Rt reversed course and began increasing by 0.007 units per day (95% CI, 0.006-0.007), reaching a mean Rt of 1.16 eight weeks later, with only 9/51 jurisdictions maintaining Rt <1.0. Parallel models showed similar reversals in the growth of COVID-19 cases and deaths. Indicators often used to motivate relaxation at the time of relaxation (e.g. test positivity rate <5%) predicted greater post-relaxation epidemic growth. CONCLUSIONS: We detected an immediate and significant reversal in SARS-CoV-2 epidemic suppression after relaxation of social distancing measures across the U.S. Premature relaxation of social distancing measures undermined the country's ability to control the disease burden associated with COVID-19

Trends in alcohol-related injury admissions in adolescents in Western Australia and England: population-based cohort study

BACKGROUND: Alcohol-related harm in young people is now a global health priority. We examined trends in hospital admissions for alcohol-related injuries for adolescents in Western Australia (WA) and in England, identified groups most at risk and determined causes of injuries. METHODS: Annual incidence rates for alcohol-related injury rates were calculated using population-level hospital admissions data for WA and England. We compared trends in different types of alcohol-related injury by age and gender. RESULTS: Despite a decrease in the overall rate of injury admissions for people aged 13-17 years in WA, alcohol-related injuries have increased significantly from 1990 to 2009 (from 8 to 12 per 10 000). Conversely, alcohol-related injury rates have declined in England since 2007. In England, self-harm is the most frequently recorded cause of alcohol-related injury. In WA, unintentional injury is most common; however, violence-related harm is increasing for boys and girls. CONCLUSION: Alcohol-related harm of sufficient severity to require hospital admission is increasing among adolescents in WA. Declining trends in England suggest that this trend is not inevitable or irreversible. More needs to be done to address alcohol-related harm, and on-going monitoring is required to assess the effectiveness of strategies

Periodic pattern formation in reaction-diffusion systems -an introduction for numerical simulation

The aim of the present review is to provide a comprehensive explanation of Turing reaction–diffusion systems in sufficient detail to allow readers to perform numerical calculations themselves. The reaction–diffusion model is widely studied in the field of mathematical biology, serves as a powerful paradigm model for self-organization and is beginning to be applied to actual experimental systems in developmental biology. Despite the increase in current interest, the model is not well understood among experimental biologists, partly because appropriate introductory texts are lacking. In the present review, we provide a detailed description of the definition of the Turing reaction–diffusion model that is comprehensible without a special mathematical background, then illustrate a method for reproducing numerical calculations with Microsoft Excel. We then show some examples of the patterns generated by the model. Finally, we discuss future prospects for the interdisciplinary field of research involving mathematical approaches in developmental biology

An epidemiologic study of psychotropic medication and obesity-related chronic illnesses in older psychiatric patients

Objective: Adverse effects from medication vary with age. Weight gain with several psychotropics is well known in adults but less information is available related to extent and complications of psychotropic-induced weight gain in older psychiatric patients. We determined the relative incidence of 2 obesity-related conditions (diabetes and hypertension) in older psychiatric patients receiving antipsychotics, antidepressants, and mood stabilizers. Method: A population-based case-control study of all psychiatric patients aged 67 years or older in contact with either specialist services or primary care using administrative data from Nova Scotia. Results: We identified incident cases of diabetes (n = 608) and of hypertension (n = 1056), as well as an equal number of control subjects for each condition. Amitryptiline, selective serotonin reuptake inhibitors (SSRIs), and olanzapine were associated with an increased risk of presenting with hypertension 6 months after initial prescription. By contrast, conventional antipsychotics were associated with a reduced incidence of hypertension. Olanzapine was also significantly associated with diabetes after 6 months (OR = 2.58, 95% CI 1.12 to 5.92). The findings for SSRIs and olanzapine remained significant after adjusting for potential confounders such as sociodemographic characteristics, schizophrenia, beta blockers, thiazide diuretics, and corticosteroids. Conclusions: Our results suggest that the association of psychotropics and 2 obesity-related conditions, hypertension and diabetes, applies to older psychiatric patients as well as younger populations. Within drug classes, there are drugs that have a greater association than others, and this may be a factor when choosing a specific agent

The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance

Modes, mechanisms and evidence of bet hedging in rotifer diapause traits

In this contribution, we review our knowledge on bet-hedging strategies associated with rotifer diapause. First, we describe the ecological scenario under which bet hedging is likely to have evolved in three diapause-related traits in monogonont rotifer populations: (1) the timing of sex (because diapausing eggs are produced via sexual reproduction), (2) the sexual reproduction ratio (i.e. the fraction of sexually reproducing females) and (3) the timing of diapausing egg hatching. Then, we describe how to discriminate among bet-hedging modes and discuss which modes and mechanisms better fit the variability observed in these traits in rotifers. Finally, we evaluate the strength of the empirical evidence for bet hedging in the scarce studies available, and we call for the need of research at different levels of biological complexity to fully understand bet hedging in rotifer diapause

Health Data Linkage for Public Interest Research in the UK: Key Obstacles and Solutions

ntroduction: Analysis of linked health data can generate important, even life-saving, insights into populationhealth. Yet obstacles both legal and organisational in nature can impede this work. Approach: We focus on three UK infrastructures set up to link and share data for research: the AdministrativeData Research Network, NHS Digital, and the Secure Anonymised Information Linkage Databank.Bringing an interdisciplinary perspective, we identify key issues underpinning their challenges andsuccesses in linking health data for research. Results:We identify examples of uncertainty surrounding legal powers to share and link data, and around dataprotection obligations, as well as systemic delays and historic public backlash. These issues requireupdated official guidance on the relevant law, approaches to linkage which are planned for impactand ongoing utility, greater transparency between data providers and researchers, and engagementwith the patient population which is both high-profile and carefully considered.ConclusionsHealth data linkage for research presents varied challenges, to which there can be no single solution.Our recommendations would require action from a number of data providers and regulators tobe meaningfully advanced. This illustrates the scale and complexity of the challenge of health datalinkage, in the UK and beyond: a challenge which our case studies suggest no single organisation cancombat alone. Planned programmes of linkage are critical because they allow time for organisationsto address these challenges without adversely affecting the feasibility of individual research project

The dynamic mosaic phenotypes of flowering plants

Ecological interaction and adaptation both depend on phenotypic characteristics. In contrast with the common conception of the ‘adult’ phenotype, plant bodies develop continuously during their lives. Furthermore, the different units (metamers) that comprise plant bodies are not identical copies, but vary extensively within individuals. These characteristics foster recognition of plant phenotypes as dynamic mosaics. We elaborate this conception based largely on a wide‐ranging review of developmental, ecological and evolutionary studies of plant reproduction, and identify its utility in the analysis of plant form, function and diversification. An expanded phenotypic conception is warranted because dynamic mosaic features affect plant performance and evolve. Evidence demonstrates that dynamic mosaic phenotypes enable functional ontogeny, division of labour, resource and mating efficiency. In addition, dynamic mosaic features differ between individuals and experience phenotypic selection. Investigation of the characteristics and roles of dynamic and mosaic features of plant phenotypes benefits from considering within‐individual variation as a function‐valued trait that can be analysed with functional data methods. Phenotypic dynamics and within‐individual variation arise despite an individual's genetic uniformity, and develop largely by heterogeneous gene expression and associated hormonal control. These characteristics can be heritable, so that dynamic mosaic phenotypes can evolve and diversify by natural selection.Fil: Harder, Lawrence. University of Calgary; CanadáFil: Strelin, Marina Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Universidad Nacional Autónoma de México. Departamento de Ecología Evolutiva. Instituto de Ecología; MéxicoFil: Clocher, Ilona C.. University of Calgary; CanadáFil: Kulbaba, Mason. University of Calgary; CanadáFil: Aizen, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentin

Mechanically activated Piezo1 channels of cardiac fibroblasts stimulate p38 mitogen-activated protein kinase activity and interleukin-6 secretion

Piezo1 is a mechanosensitive cation channel with widespread physiological importance; however, its role in the heart is poorly understood. Cardiac fibroblasts help preserve myocardial integrity and play a key role in regulating its repair and remodeling following stress or injury. Here we investigated Piezo1 expression and function in cultured human and mouse cardiac fibroblasts. RT-PCR experiments confirmed that Piezo1 mRNA in cardiac fibroblasts is expressed at levels similar to those in endothelial cells. The results of a Fura-2 intracellular Ca2+ assay validated Piezo1 as a functional ion channel that is activated by its agonist, Yoda1. Yoda1-induced Ca2+ entry was inhibited by Piezo1 blockers (gadolinium and ruthenium red) and was reduced proportionally by siRNA-mediated Piezo1 knockdown or in murine Piezo1+/− cells. Results from cell-attached patch clamp recordings on human cardiac fibroblasts established that they contain mechanically activated ion channels and that their pressure responses are reduced by Piezo1 knockdown. Investigation of Yoda1 effects on selected remodeling genes indicated that Piezo1 activation increases both mRNA levels and protein secretion of IL-6, a pro-hypertrophic and profibrotic cytokine, in a Piezo1-dependent manner. Moreover, Piezo1 knockdown reduced basal IL-6 expression from cells cultured on softer collagen-coated substrates. Multiplex kinase activity profiling combined with kinase inhibitor experiments and phosphospecific immunoblotting established that Piezo1 activation stimulates IL-6 secretion via the p38 mitogen-activated protein kinase downstream of Ca2+ entry. In summary, cardiac fibroblasts express mechanically activated Piezo1 channels coupled to secretion of the paracrine signaling molecule IL-6. Piezo1 may therefore be important in regulating cardiac remodeling