The challenge of consent in clinical genome-wide testing.

Genome-wide testing methods include array comparative genomic hybridisation (aCGH), multiple gene panels, whole exome sequencing (WE) and whole genome sequencing (WGS). Here we introduce some of the key ethical and social considerations relating to informed consent for the testing of children, particularly the management of incidental findings and variants of unknown significance.

Cognitive performance and psychosocial functioning in patients with bipolar disorder, unaffected siblings, and healthy controls.

Objective:: To assess cognitive performance and psychosocial functioning in patients with bipolar disorder (BD), in unaffected siblings, and in healthy controls.

Methods:: Subjects were patients with BD (n=36), unaffected siblings (n=35), and healthy controls (n=44). Psychosocial functioning was accessed using the Functioning Assessment Short Test (FAST).

Engaging Pacific Islanders in Research: Community Recommendations.

Background: Health disparities continue to persist among Native Hawaiian and Pacific Islander (NHPI) communities.

Objectives: This study sought to understand the perspectives of community organizations in the Ulu Network on how researchers can collaborate with communities to promote community wellness.

Methods: Key informant interviews and small group interviews were conducted with the leadership in the Ulu Network.

The Activators of Cyclin-Dependent Kinase 5 p35 and p39 Are Essential for Oligodendrocyte Maturation, Process Formation, and Myelination.

The regulation of oligodendrocyte development and myelin formation in the CNS is poorly defined. Multiple signals influence the rate and extent of CNS myelination, including the noncanonical cyclin-dependent kinase 5 (Cdk5) whose functions are regulated by its activators p35 and p39. Here we show that selective loss of either p35 or p39 perturbed specific aspects of oligodendrocyte development, whereas loss of both p35 and p39 completely inhibited the development of mature oligodendrocytes and myelination.

The rise of novelty in ecosystems.

Rapid and ongoing change creates novelty in ecosystems everywhere, both when comparing contemporary systems to their historical baselines, and predicted future systems to the present. However, the level of novelty varies greatly among places. Here we propose a formal and quantifiable definition of abiotic and biotic novelty in ecosystems, map abiotic novelty globally, and discuss the implications of novelty for the science of ecology and for biodiversity conservation.

Cerebral Microdialysis.

A variety of neuromonitoring techniques are available to aid in the care of neurocritically ill patients. However, traditional monitors lack the ability to measure brain biochemistry and may provide inadequate warning of potentially reversible deleterious conditions. Cerebral microdialysis (CMD) is a safe, novel method of monitoring regional brain biochemistry.

Massively parallel sequencing of phyllodes tumours of the breast reveals actionable mutations, and TERT promoter hotspot mutations and TERT gene amplification as likely drivers of progression.

Phyllodes tumours (PTs) are breast fibroepithelial lesions that are graded based on histological criteria as benign, borderline or malignant. PTs may recur locally. Borderline PTs and malignant PTs may metastasize to distant sites.

Improved DFT Potential Energy Surfaces via Improved Densities.

Density-corrected DFT is a method that cures several failures of self-consistent semilocal DFT calculations by using a more accurate density instead. A novel procedure employs the Hartree-Fock density to bonds that are more severely stretched than ever before. This substantially increases the range of accurate potential energy surfaces obtainable from semilocal DFT for many heteronuclear molecules.

Silk Fibroin Aqueous-Based Adhesives Inspired by Mussel Adhesive Proteins.

Silk fibroin from the domesticated silkworm Bombyx mori is a naturally occurring biopolymer with charged hydrophilic terminal regions that end-cap a hydrophobic core consisting of repeating sequences of glycine, alanine, and serine residues. Taking inspiration from mussels that produce proteins rich in L-3,4-dihydroxyphenylalanine (DOPA) to adhere to a variety of organic and inorganic surfaces, the silk fibroin was functionalized with catechol groups. Silk fibroin was selected for its high molecular weight, tunable mechanical and degradation properties, aqueous processability, and wide availability.

Using second harmonic generation to predict patient outcome in solid tumors.

Background: Over-treatment of estrogen receptor positive (ER+), lymph node-negative (LNN) breast cancer patients with chemotherapy is a pressing clinical problem that can be addressed by improving techniques to predict tumor metastatic potential. Here we demonstrate that analysis of second harmonic generation (SHG) emission direction in primary tumor biopsies can provide prognostic information about the metastatic outcome of ER+, LNN breast cancer, as well as stage 1 colorectal adenocarcinoma.

Methods: SHG is an optical signal produced by fibrillar collagen.

Uterine adenosarcomas are mesenchymal neoplasms.

Uterine adenosarcomas (UAs) are biphasic lesions composed of a malignant mesenchymal (ie stromal) component and an epithelial component. UAs are generally low-grade and have a favourable prognosis, but may display sarcomatous overgrowth (SO), which is associated with a worse outcome. We hypothesized that, akin to breast fibroepithelial lesions, UAs are mesenchymal neoplasms in which clonal somatic genetic alterations are restricted to the mesenchymal component.

Residue-by-Residue View of In Vitro FUS Granules that Bind the C-Terminal Domain of RNA Polymerase II.

Phase-separated states of proteins underlie ribonucleoprotein (RNP) granules and nuclear RNA-binding protein assemblies that may nucleate protein inclusions associated with neurodegenerative diseases. We report that the N-terminal low-complexity domain of the RNA-binding protein Fused in Sarcoma (FUS LC) is structurally disordered and forms a liquid-like phase-separated state resembling RNP granules. This state directly binds the C-terminal domain of RNA polymerase II.

Phase I Study of the Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (TAK-924/MLN4924) in Patients with Advanced Solid Tumors.

Purpose: To determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the investigational NEDD8-activating enzyme (NAE) inhibitor pevonedistat (TAK-924/MLN4924) and to investigate pevonedistat pharmacokinetics and pharmacodynamics in patients with advanced nonhematologic malignancies.

Experimental Design: Pevonedistat was administered via 60-minute intravenous infusion on days 1 to 5 (schedule A, n = 12), or days 1, 3, and 5 (schedules B, n = 17, and C, n = 19) of 21-day cycles. Schedule B included oral dexamethasone 8 mg before each pevonedistat dose.

Delivery of cognitive behavioural therapy to workers: a systematic review.

Background: Cognitive behavioural therapy (CBT) is a key intervention, enabling workers on sick leave with common mental health problems to return to work. It can be delivered by a variety of methods including face-to-face therapy and the Internet. It is not known which is the optimal method of delivery.

The Hubbard dimer: a density functional case study of a many-body problem.

This review explains the relationship between density functional theory and strongly correlated models using the simplest possible example, the two-site Hubbard model. The relationship to traditional quantum chemistry is included. Even in this elementary example, where the exact ground-state energy and site occupations can be found analytically, there is much to be explained in terms of the underlying logic and aims of density functional theory.

Enzymatically-responsive pro-angiogenic peptide-releasing poly(ethylene glycol) hydrogels promote vascularization in vivo.

Therapeutic angiogenesis holds great potential for a myriad of tissue engineering and regenerative medicine approaches. While a number of peptides have been identified with pro-angiogenic behaviors, therapeutic efficacy is limited by poor tissue localization and persistence. Therefore, poly(ethylene glycol) hydrogels providing sustained, enzymatically-responsive peptide release were exploited for peptide delivery.

Fe en Accion/Faith in Action: Design and implementation of a church-based randomized trial to promote physical activity and cancer screening among churchgoing Latinas.

Objectives: To describe both conditions of a two-group randomized trial, one that promotes physical activity and one that promotes cancer screening, among churchgoing Latinas. The trial involves promotoras (community health workers) targeting multiple levels of the Ecological Model. This trial builds on formative and pilot research findings.

Community Health Workers Promoting Physical Activity: Targeting Multiple Levels of the Social Ecological Model.

The effectiveness of community health workers (CHWs) as health educators and health promoters among Latino populations is widely recognized. The Affordable Care Act created important opportunities to increase the role of CHWs in preventive health. This article describes the implementation of CHW-led, culturally specific, faith-based program to increase physical activity among churchgoing Latinas.

Parent distress reactions following a serious illness or injury in their child: a protocol paper for the take a Breath Cohort Study.

Background: Diagnosis of life threatening childhood illness or injury can lead to significant distress reactions in parents, with many experiencing clinically significant levels of post-traumatic stress symptoms. These symptoms can have long-term adverse impacts on parent mental health, family functioning, and the adjustment of the ill child. Independent studies have found such reactions in several different illness groups.

Temporally tunable, enzymatically responsive delivery of proangiogenic peptides from poly(ethylene glycol) hydrogels.

Proangiogenic drugs hold great potential to promote reperfusion of ischemic tissues and in tissue engineering applications, but efficacy is limited by poor targeting and short half-lives. Methods to control release duration or provide enzymatically responsive drug delivery have independently improved drug efficacy. However, no material has been developed to temporally control the rate of enzymatically responsive drug release.

Lyophilized Silk Sponges: A Versatile Biomaterial Platform for Soft Tissue Engineering.

We present a silk biomaterial platform with highly tunable mechanical and degradation properties for engineering and regeneration of soft tissues such as, skin, adipose, and neural tissue, with elasticity properties in the kilopascal range. Lyophilized silk sponges were prepared under different process conditions and the effect of silk molecular weight, concentration and crystallinity on 3D scaffold formation, structural integrity, morphology, mechanical and degradation properties, and cell interactions in vitro and in vivo were studied. Tuning the molecular weight distribution (via degumming time) of silk allowed the formation of stable, highly porous, 3D scaffolds that held form with silk concentrations as low as 0.

Developing an educational dvd on the use of hand massage in the care of people with dementia: An innovation.

The world's population is ageing and while the vast majority of older people live independently, a significant number will develop dementia. Communication and interpersonal skills are essential in developing relationships. People with dementia may have complex health needs and may have limited language capacity and therefore the use of presence and touch and more specifically hand massage gains greater significance for their wellbeing.

Can a secondary isotope effect be larger than a primary?

Primary and secondary (18)O equilibrium isotope effects on the acidities of a variety of Brønsted and Lewis acids centered on carbon, boron, nitrogen, and phosphorus were computed by density-functional theory. For many of these acids, the secondary isotope effect was found to be larger than the primary isotope effect. This is a counterintuitive result, because the H atom that is lost is closer to the (18)O atom that is responsible for the primary isotope effect.