Dynamic skin behaviors in cephalopods.

The coleoid cephalopods (cuttlefish, octopus, and squid) are a group of soft-bodied mollusks that exhibit a wealth of complex behaviors, including dynamic camouflage, object mimicry, skin-based visual communication, and dynamic body patterns during sleep. Many of these behaviors are visually driven and engage the animals' color changing skin, a pixelated display that is directly controlled by neurons projecting from the brain. Thus, cephalopod skin provides a direct readout of neural activity in the brain.

Phased nanopore assembly with Shasta and modular graph phasing with GFAse.

Reference-free genome phasing is vital for understanding allele inheritance and the impact of single-molecule DNA variation on phenotypes. To achieve thorough phasing across homozygous or repetitive regions of the genome, long-read sequencing technologies are often used to perform phased de novo assembly. As a step toward reducing the cost and complexity of this type of analysis, we describe new methods for accurately phasing Oxford Nanopore Technologies (ONT) sequence data with the Shasta genome assembler and a modular tool for extending phasing to the chromosome scale called GFAse.

Extravasation of Non-Cytotoxic Drugs in Older People.

To describe the risk factors of extravasation, its impact on the pharmacokinetics of non-cytotoxic drugs, and management of extravasation in older individuals. Extravasation occurs when vesicants leak from blood vessels into surrounding tissue causing severe injury such as tissue necrosis while infiltration is caused by leakage of an irritant that causes injury but does not lead to tissue necrosis. Extravasation occurs in approximately 0.

Neural control of cephalopod camouflage.

In Die Another Day, James Bond receives an Aston Martin that can render itself invisible by dynamically reproducing the surroundings on the car's "polymer skin". In what is widely regarded as the worst Bond movie ever, the invisible car scene is cited as the moment the plot plunges into the truly absurd. But what if nature had actually invented such a technology, and did so hundreds of millions of years ago? The coleoid cephalopods - octopus, cuttlefish and squid - are living examples of dynamic camouflage.

Molecular mechanisms controlling the biogenesis of the TGF-β signal Vg1.

The TGF-beta signals Vg1 (Dvr1/Gdf3) and Nodal form heterodimers to induce vertebrate mesendoderm. The Vg1 proprotein is a monomer retained in the endoplasmic reticulum (ER) and is processed and secreted upon heterodimerization with Nodal, but the mechanisms underlying Vg1 biogenesis are largely elusive. Here, we clarify the mechanisms underlying Vg1 retention, processing, secretion, and signaling and introduce a Synthetic Processing (SynPro) system that enables the programmed cleavage of ER-resident and extracellular proteins.

Creation of an albino squid line by CRISPR-Cas9 and its application for in vivo functional imaging of neural activity.

Cephalopods are remarkable among invertebrates for their cognitive abilities, adaptive camouflage, novel structures, and propensity for recoding proteins through RNA editing. Due to the lack of genetically tractable cephalopod models, however, the mechanisms underlying these innovations are poorly understood. Genome editing tools such as CRISPR-Cas9 allow targeted mutations in diverse species to better link genes and function.

A brain atlas for the camouflaging dwarf cuttlefish, Sepia bandensis.

The coleoid cephalopods (cuttlefish, octopus, and squid) are a group of soft-bodied marine mollusks that exhibit an array of interesting biological phenomena, including dynamic camouflage, complex social behaviors, prehensile regenerating arms, and large brains capable of learning, memory, and problem-solving. The dwarf cuttlefish, Sepia bandensis, is a promising model cephalopod species due to its small size, substantial egg production, short generation time, and dynamic social and camouflage behaviors. Cuttlefish dynamically camouflage to their surroundings by changing the color, pattern, and texture of their skin.

Phased nanopore assembly with Shasta and modular graph phasing with GFAse.

As a step towards simplifying and reducing the cost of haplotype resolved assembly, we describe new methods for accurately phasing nanopore data with the Shasta genome assembler and a modular tool for extending phasing to the chromosome scale called GFAse. We test using new variants of Oxford Nanopore Technologies' (ONT) PromethION sequencing, including those using proximity ligation and show that newer, higher accuracy ONT reads substantially improve assembly quality.

Embryonic development of the camouflaging dwarf cuttlefish, Sepia bandensis.

Background: The dwarf cuttlefish Sepia bandensis, a camouflaging cephalopod from the Indo-Pacific, is a promising new model organism for neuroscience, developmental biology, and evolutionary studies. Cuttlefish dynamically camouflage to their surroundings by altering the color, pattern, and texture of their skin. The skin's "pixels" (chromatophores) are controlled by motor neurons projecting from the brain.

Access and quality of health care in Canada: Insights from 1998 to the present.

This article reviews perceptions of Canada's public and health professionals regarding access and quality of healthcare. Principal data sources were 13 sequential Health Care in Canada (HCIC) surveys, from 1998 to 2018. Over time, the data series reveals that an increasing majority of the public report receiving quality care, rising from a national average of 53% in 2002 to 61% in 2018.

Canada's Evolving Medicare: End-of-Life Care.

A challenging issue in contemporary Canadian Medicare is the evolution of end-of-life care. Utilizing data from the 2016 and 2018 Health Care in Canada (HCIC) surveys, this paper compares the support and priorities of the adult public (n = 1500), health professionals (n = 400), and administrators (n = 100) regarding key components for end-of-life care just prior to and post legalization of medical assistance in dying (MAiD) in Canada. In 2016 and 2018, the public, health professionals and administrators strongly supported enhanced availability of all proposed end-of-life care options: pain management, hospice and palliative care, home care supports, and medically assisted death.

Randomized Trials of Retosiban Versus Placebo or Atosiban in Spontaneous Preterm Labor.

Objective: The aim of this study is to assess the efficacy and safety of retosiban in spontaneous preterm labor (sPTL).

Study Design: Two multicenter, randomized, and double-blind trials compared retosiban with placebo and retosiban with atosiban in women with a singleton pregnancy and intact membranes in sPTL at 24 to 33 weeks' gestation. Coprimary endpoints in the placebo-controlled trial were time to delivery (TTD) or treatment failure (whichever occurred first) and neonatal composite morbidity and mortality.

Canada's Evolving Medicare: Patient-Centred Care.

Canada's universal healthcare program, medicare, continues to evolve. An area of care that has gained increasing attention over the past several years is the general concept and specific components of patient centricity in healthcare delivery. This paper compares key measures of patient-centred care practices recorded in the 2013 and 2016 Health Care in Canada (HCIC) surveys, with the most recent preferences of the public and health professionals obtained in the 2018 HCIC survey, including priorities for improved future care.

Non-Adherence to Prescribed Therapies: Pharmacare's Existential Challenge.

Pharmacare, a recently proposed addition to Canada's universal medicare program, has become a prominent topic in the public discourse, but funding and leadership have not been established. Repeated Health Care in Canada (HCIC) surveys of the adult public and a broad spectrum of health professionals reveal very strong support for a national system that is easy to access and covers all prescribed pharmaceuticals. Although the practical details of universal pharmacare remain to be established, there is strong support among the public and professionals as well as increasing federal government interest in moving forward and ultimately implementing pharmacare.

Medicare's Evolution: National Pharmacare and Shared Leadership.

Repeated Health Care in Canada (HCIC) surveys over the past two decades have consistently reported that the adult public and clinical and administrative health professionals consider medicare to be successful in terms of quality of care, despite a growing concern that timely access to care remains challenging. These key stakeholders have also recently signalled that major change strategies are likely necessary for continuing success. In the 2018 survey, both the public and professionals ranked highest the creation of a national comprehensive pharmacare plan, entirely funded by the federal government, or with federal funding for those not currently covered by existing pharmaceutical plans.

CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing.

The CRISPR-Cas system is a powerful genome editing tool that functions in a diverse array of organisms and cell types. The technology was initially developed to induce targeted mutations in DNA, but CRISPR-Cas has now been adapted to target nucleic acids for a range of purposes. CHOPCHOP is a web tool for identifying CRISPR-Cas single guide RNA (sgRNA) targets.

Dissolution and Translational Modeling Strategies Toward Establishing an In Vitro-In Vivo Link-a Workshop Summary Report.

This publication summarizes the proceedings of day 2 of a 3-day workshop on "Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development." Patient-centric drug product development from a drug product quality perspective necessitates the establishment of clinically relevant drug product specifications via an in vitro-in vivo link. Modeling and simulation offer a path to establish this link; in this regard, physiologically based modeling has been implemented successfully to support regulatory decision-making and drug product labeling.

Conserved regulation of Nodal-mediated left-right patterning in zebrafish and mouse.

Nodal is the major effector of left-right axis development. In mice, Nodal forms heterodimers with Gdf1 and is inhibited by Cerl2/Dand5 at the node, and by Lefty1 in the lateral plate mesoderm (LPM). Studies in zebrafish have suggested some parallels, but also differences, between left-right patterning in mouse and zebrafish.

Gene expression studies using a miniaturized thermal cycler system on board the International Space Station.

The distance and duration of human spaceflight missions is set to markedly increase over the coming decade as we prepare to send astronauts to Mars. However, the health impact of long-term exposure to cosmic radiation and microgravity is not fully understood. In order to identify the molecular mechanisms underpinning the effects of space travel on human health, we must develop the capacity to monitor changes in gene expression and DNA integrity in space.

Healthcare in Canada: Choices Going Forward.

The overarching purpose of serial Health Care in Canada (HCIC) surveys of the adult Canadian public and a broad spectrum of healthcare professionals over the past two decades has been the development of an evidence-based map to inform strategic and clinical decisions to improve care and outcomes for Canadians. Recent surveys reveal a growing concern that medicare may require complete rebuilding or major strategic repairs. On the other hand, a majority of stakeholders perceive continuing underlying quality in our clinical care and look forward to both system- and patient-centred initiatives to improve future care.

Better decision making in drug development through adoption of formal prior elicitation.

With the continued increase in the use of Bayesian methods in drug development, there is a need for statisticians to have tools to develop robust and defensible informative prior distributions. Whilst relevant empirical data should, where possible, provide the basis for such priors, it is often the case that limitations in data and/or our understanding may preclude direct construction of a data-based prior. Formal expert elicitation methods are a key technique that can be used to determine priors in these situations.

A Retrospective Database Analysis of Neonatal Morbidities to Evaluate a Composite Endpoint for Use in Preterm Labor Clinical Trials.

 To propose and assess a composite endpoint (CE) of neonatal benefit based on neonatal mortality and morbidities by gestational age (GA) for use in preterm labor clinical trials.  A descriptive, retrospective analysis of the Medical University of South Carolina Perinatal Information System database was conducted. Neonatal morbidities were assessed for inclusion in the CE based on clinical significance/risk of childhood neurodevelopmental impairment, frequency, and association with GA in a mother-neonate linked cohort, comprising women with uncomplicated singleton pregnancies delivered at ≥24 weeks' GA.

Assessing a composite end point for new tocolytics in clinical trials: Data from 4 US integrated delivery networks.

Purpose: A composite end point (CE) measuring neonatal benefit was created for use in tocolytic randomized controlled trials with rates assessed using data from one referral hospital. The goal of this study was to assess wider generalizability of the CE, using data from multiple integrated delivery networks, creating a cohort of linked mother-neonate pairs to understand neonatal outcomes in a broad population.

Methods: Retrospective data on births (2001-2012) were collected from 4 US integrated delivery networks in the COMparative effectiveness PAtient Safety and Surveillance (COMPASS) Research Network, and linked mother-neonate pairs were identified.

Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm.

Nodal is considered the key inducer of mesendoderm in vertebrate embryos and embryonic stem cells. Other TGF-beta-related signals, such as Vg1/Dvr1/Gdf3, have also been implicated in this process but their roles have been unclear or controversial. Here we report that zebrafish embryos without maternally provided fail to form endoderm and head and trunk mesoderm, and closely resemble loss-of-function mutants.