A Four-Biomarker Blood Signature Discriminates Systemic Inflammation Due to Viral Infection Versus Other Etiologies.

The innate immune system of humans and other mammals responds to pathogen-associated molecular patterns (PAMPs) that are conserved across broad classes of infectious agents such as bacteria and viruses. We hypothesized that a blood-based transcriptional signature could be discovered indicating a host systemic response to viral infection. Previous work identified host transcriptional signatures to individual viruses including influenza, respiratory syncytial virus and dengue, but the generality of these signatures across all viral infection types has not been established.

Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels.

The spatial presentation of mechanical information is a key parameter for cell behavior. We have developed a method of polymerization control in which the differential diffusion distance of unreacted cross-linker and monomer into a prepolymerized hydrogel sink results in a tunable stiffness gradient at the cell-matrix interface. This simple, low-cost, robust method was used to produce polyacrylamide hydrogels with stiffness gradients of 0.

Vaccine-based immunotherapeutic approaches to gliomas and beyond.

Astrocytic and oligodendroglial gliomas are intrinsic brain tumours characterized by infiltrative growth and resistance to classic cancer therapies, which renders them inevitably lethal. Glioblastoma, the most common type of glioma, also exhibits neoangiogenesis and profound immunosuppressive properties. Accordingly, strategies to revert glioma-associated immunosuppression and promote tumour-directed immune responses have been extensively explored in rodent models and in large clinical trials of tumour immunotherapy.

Long-term Survival in Glioblastoma with Cytomegalovirus pp65-Targeted Vaccination.

Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can extend survival and, in a separate study, that dose-intensified temozolomide (DI-TMZ) and adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) potentiate tumor-specific immune responses in patients with glioblastoma. Here, we evaluated pp65-specific cellular responses following DI-TMZ with pp65-DCs and determined the effects on long-term progression-free survival (PFS) and overall survival (OS).

Development of an interface-focused educational complex intervention.

Background: In many countries, the medical primary-secondary care interface is central to the delivery of quality patient care. There is prevailing interest in developing initiatives to improve interface working for the benefit of health care professionals and their patients.

Aim: To describe the development of an educational intervention designed to improve working at the primary-secondary care interface in NHS Scotland (United Kingdom) within the context of the Medical Research Council framework for the development and evaluation of complex interventions.

Directional Limits on Persistent Gravitational Waves from Advanced LIGO's First Observing Run.

We employ gravitational-wave radiometry to map the stochastic gravitational wave background expected from a variety of contributing mechanisms and test the assumption of isotropy using data from the Advanced Laser Interferometer Gravitational Wave Observatory's (aLIGO) first observing run. We also search for persistent gravitational waves from point sources with only minimal assumptions over the 20-1726 Hz frequency band. Finding no evidence of gravitational waves from either point sources or a stochastic background, we set limits at 90% confidence.

Upper Limits on the Stochastic Gravitational-Wave Background from Advanced LIGO's First Observing Run.

A wide variety of astrophysical and cosmological sources are expected to contribute to a stochastic gravitational-wave background. Following the observations of GW150914 and GW151226, the rate and mass of coalescing binary black holes appear to be greater than many previous expectations. As a result, the stochastic background from unresolved compact binary coalescences is expected to be particularly loud.

Erythritol and Lufenuron Detrimentally Alter Age Structure of Wild Drosophila suzukii (Diptera: Drosophilidae) Populations in Blueberry and Blackberry.

We report on the efficacy of 0.5 M (61,000 ppm) erythritol (E) in Truvia Baking Blend, 10 ppm lufenuron (L), and their combination (LE) to reduce egg and larval densities of wild populations of Drosophila suzukii (Matsumura) infesting fields of rabbiteye blueberries (Vaccinium virgatum) and blackberries (Rubus sp.).

Loss-of-Function Mutations in LGI4, a Secreted Ligand Involved in Schwann Cell Myelination, Are Responsible for Arthrogryposis Multiplex Congenita.

Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through genetic mapping of disease loci and whole-exome sequencing in four unrelated multiplex families presenting with severe AMC, we identified biallelic loss-of-function mutations in LGI4 (leucine-rich glioma-inactivated 4). LGI4 is a ligand secreted by Schwann cells that regulates peripheral nerve myelination via its cognate receptor ADAM22 expressed by neurons.

Prospect of rindopepimut in the treatment of glioblastoma.

Rindopepimut (CDX-110) is a peptide vaccine that targets epidermal growth factor receptor variant III (EGFRvIII), a tumor-specific epitope expressed in the most common and lethal primary malignant neoplasm of the brain - glioblastoma (GBM). Areas covered: The EGFRvIII mutation introduces an 801 base pair in-frame deletion of the extracellular domain of the transmembrane tyrosine kinase, resulting in constitutive kinase activity, amplification of cell growth, and inhibition of apoptosis. Rindopepimut contains a 14mer amino acid peptide spanning the EGFRvIII mutation site that is conjugated to keyhole limpet hemocyanin (KLH).

Poorer Arthroscopic Outcomes of Mild Dysplasia With Cam Femoroacetabular Impingement Versus Mixed Femoroacetabular Impingement in Absence of Capsular Repair.

Purpose: To compare outcomes of mild dysplasia with cam femoroacetabular impingement (FAI) vs mixed FAI with hip arthroscopy without capsular repair.

Methods: A retrospective review of a 2009 to 2010 multicenter prospective outcome study was performed comparing a cohort with mild dysplasia and cam femoroacetabular impingement (cohort D) to a cohort with mixed FAI (cohort M). Outcome measures included Nonarthritic Hip Score (NAHS) and satisfaction with minimum 2-year follow-up.

A pilot validation study of crowdsourcing systematic reviews: update of a searchable database of pediatric clinical trials of high-dose vitamin D.

Background: Completing large systematic reviews and maintaining them up to date poses significant challenges. This is mainly due to the toll required of a small group of experts to screen and extract potentially eligible citations. Automated approaches have failed so far in providing an accessible and adaptable tool to the research community.

Heat exposure and productivity in orchards: Implications for climate change research.

Recent studies suggest that heat exposure degrades work productivity, but such studies have not considered individual- and workplace-level factors. Forty-six tree-fruit harvesters (98% Latino/a) from 6 orchards participated in a cross-sectional study in central/eastern Washington in 2015. The association between maximum measured work-shift wet-bulb globe temperature (WBGT) and productivity (total weight of fruit bins collected per time worked) was estimated using linear mixed-effects models, adjusting for relevant confounders.

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome.

Background: The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown.

Clinical practice with anti-dementia drugs: A revised (third) consensus statement from the British Association for Psychopharmacology.

The British Association for Psychopharmacology coordinated a meeting of experts to review and revise its previous 2011 guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A-D, with A having the strongest evidence base (from randomised controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and both structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography and single photon emission computerised tomography) brain imaging can improve diagnostic accuracy in particular situations (B).

Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults.

Background: Peanut allergy is common, life-threatening, and without therapeutic options. We evaluated peanut epicutaneous immunotherapy (EPIT) by using Viaskin Peanut for peanut allergy treatment.

Objective: We sought to evaluate the clinical, safety, and immunologic effects of EPIT for the treatment of peanut allergy.

Improving the care of people with dementia in general hospitals: evaluation of a whole-system train-the-trainer model.

Background: There are concerns about the quality of care that people with dementia receive in the general hospital. Staff report a lack of confidence and inadequate training in dementia care.

Methods: A train-the-trainer model was implemented across eight acute hospital trusts in London via a large academic health and science network.

An Evaluation of Accelerometer-derived Metrics to Assess Daily Behavioral Patterns.

Introduction: The way physical activity (PA) and sedentary behavior (SB) are accumulated throughout the day (i.e., patterns) may be important for health, but identifying measurable and meaningful metrics of behavioral patterns is challenging.

Mobile Health Technology Can Objectively Capture Physical Activity (PA) Targets Among African-American Women Within Resource-Limited Communities-the Washington, D.C. Cardiovascular Health and Needs Assessment.

Background: Little is understood about using mobile health (mHealth) technology to improve cardiovascular (CV) health among African-American women in resource-limited communities.

Methods: We conducted the Washington, D.C.

Undertreatment of people with major depressive disorder in 21 countries.

Background: Major depressive disorder (MDD) is a leading cause of disability worldwide.

Aims: To examine the: (a) 12-month prevalence of DSM-IV MDD; (b) proportion aware that they have a problem needing treatment and who want care; (c) proportion of the latter receiving treatment; and (d) proportion of such treatment meeting minimal standards.

Method: Representative community household surveys from 21 countries as part of the World Health Organization World Mental Health Surveys.

A Novel Strategy for Continuation ECT in Geriatric Depression: Phase 2 of the PRIDE Study.

Objective: The randomized phase (phase 2) of the Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy and tolerability of continuation ECT plus medication compared with medication alone in depressed geriatric patients after a successful course of ECT (phase 1).

Method: PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, augmented with venlafaxine.