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Penelope and her Aunt Isabel make up an exciting bedtime story about the adventures of Prince Augustus and Lady Penelope.

A quality improvement project was conducted to determine the quality of telephone nursing for patients with cancer symptoms. Eligible patients were ones who telephoned the nurse about cancer symptom(s) within four weeks prior to an emergency department (ED) visit not requiring hospital admission. Experienced oncology nurses extracting data indicated appropriateness of ED visits and opportunities for improvement. The Symptom Management Analysis Tool was used to analyze nurse documentation. For 77 patients, 87% ED visits occurred within four days of calls about symptoms (e.g., pain, breathlessness, constipation, diarrhea, nausea/vomiting) and 91% could have been managed by more complete telephone assessment and/or an urgent clinic visit. Quality of nurse documentation revealed few patients were assessed adequately (38%), received any symptom-specific medication review (49%), or were guided in self-care strategies (17%). There was low-quality telephone symptom management by nurses and a need for alternative options for patients requiring urgent face-to-face assessments. Our findings highlight a gap in use of guidelines for informing telephone symptom management.

\"A classroom guinea pig learns about gardening by growing his own pumpkin\"-- Provided by publisher.

Un projet d'amélioration de la qualité a été mené afin de mesurer la qualité des interventions téléphoniques des infirmières auprès des patients présentant des symptômes associés au cancer. Les patients admissibles au projet avaient téléphoné à une infirmière pour signaler des symptômes dans les 4 semaines précédant une visite aux urgences qui n'avait pas requis d'hospitalisation. Les infirmières spécialisées en oncologie qui ont extrait les données évaluaient la pertinence des visites aux urgences et les points à améliorer. Nous avons eu recours à un outil d'analyse de la gestion des symptômes pour analyser la documentation du personnel infirmier. Sur 77 patients, 87 % des visites aux urgences ont eu lieu durant les 4 jours suivant un appel téléphonique justifié par la présence de symptômes (douleur, dyspnée, constipation, diarrhée, nausées ou vomissements, etc.). Dans 91 % des cas, une évaluation téléphonique plus exhaustive ou une consultation dans une clinique de soins d'urgence aurait suffi. Selon la documentation laissée par les infirmières, peu de patients ont été évalués adéquatement (38 %), ont bénéficié d'une révision de la médication traitant leurs symptômes (49 %) ou ont reçu des conseils sur les stratégies de soins autoadministrés (17 %). La qualité de la prise en charge des symptômes effectuée au téléphone par les infirmières laissait à désirer et il aurait fallu trouver des solutions de rechange pour les patients nécessitant une évaluation d'urgence en personne. Ces constats font ressortir des lacunes dans l'utilisation des directives sur la gestion téléphonique des symptômes.

In the Rainforest looks at the most vibrant ecosystem on our planet. The rainforest is home to millions of plant and animal species. Some animals live high up in the trees, some crawl across the forest floor, and some tunnel underground, but they all depend on one another and the rain to survive.

CRISPR–Cas9 mediated genome editing offers unprecedented opportunities for treating human diseases. There are several reports that demonstrate pre-existing immune responses to Cas9 which may have implications for clinical development of CRISPR-Cas9 mediated gene therapy. Here we use 209 overlapping peptides that span the entire sequence of Staphylococcus aureus Cas9 (SaCas9) and human peripheral blood mononuclear cells (PBMCs) from a cohort of donors with a distribution of Major Histocompatibility Complex (MHC) alleles comparable to that in the North American (NA) population to identify the immunodominant regions of the SaCas9 protein. We also use an MHC Associated Peptide Proteomics (MAPPs) assay to identify SaCas9 peptides presented by MHC Class II (MHC-II) proteins on dendritic cells. Using these two data sets we identify 22 SaCas9 peptides that are both presented by MHC-II proteins and stimulate CD4 + T-cells. There have been reports of immune responses against Cas9 which may impair clinical use. Here the authors scan a cohort comparable to the North American population vis-à-vis distribution of MHC-II variants to identify Cas9 peptides presented by MHC-II proteins and can stimulate CD4 + T-cells.

While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants. An expert panel adjudicated the indications, contraindications, efficacy, and evidence-of-efficacy of 9911 drug, device, dietary, and surgical interventions for 563 severe, childhood, genetic diseases. The 421 (75%) diseases and 1527 (15%) effective interventions retained are integrated with 13 genetic disease information resources and appended to diagnostic reports ( https://gtrx.radygenomiclab.com ). This system provided correct diagnoses in four retrospectively and two prospectively tested infants. The Genome-to-Treatment system facilitates optimal outcomes in children with rapidly progressive genetic diseases. Rapid diagnosis and implementation of treatments is crucial in many genetic conditions. Here the authors describe Genome-to-Treatment, a virtual disease management system that can achieve a rapid diagnosis by expedited whole genome sequencing in 13.5 hours and provide guidance to clinicians for possible therapies.

When B cells encounter antigens on the surface of an antigen-presenting cell (APC), B cell receptors (BCRs) are gathered into microclusters that recruit signaling enzymes. These microclusters then move centripetally and coalesce into the central supramolecular activation cluster of an immune synapse. The mechanisms controlling BCR organization during immune synapse formation, and how this impacts BCR signaling, are not fully understood. We show that this coalescence of BCR microclusters depends on the actin-related protein 2/3 (Arp2/3) complex, which nucleates branched actin networks. Moreover, in murine B cells, this dynamic spatial reorganization of BCR microclusters amplifies proximal BCR signaling reactions and enhances the ability of membrane-associated antigens to induce transcriptional responses and proliferation. Our finding that Arp2/3 complex activity is important for B cell responses to spatially restricted membrane-bound antigens, but not for soluble antigens, highlights a critical role for Arp2/3 complex-dependent actin remodeling in B cell responses to APC-bound antigens.

The Southeast accounted for most HIV diagnoses (52%) in the United States in 2015. Primary care providers (PCPs) play a vital role in HIV prevention for at-risk persons and treatment of persons living with HIV. We studied HIV-related training, knowledge, and clinical practices among PCPs in the Southeast to address knowledge gaps to inform HIV prevention strategies. Between April and August 2017, we conducted an on-line survey of a representative sample of PCPs in six Southeast jurisdictions with high rates of HIV diagnoses (Atlanta; Baltimore; Baton Rouge; District of Columbia; Miami; New Orleans). We defined HIV-related training as self-reported completion of any certified HIV/STD course or continuing education in past 24 months (prior to survey completion). We assessed associations between training and HIV testing practices, familiarity with nonoccupational post-exposure prophylaxis (nPEP) and pre-exposure prophylaxis (PrEP), and ever prescribing nPEP or PrEP. There were 820 participants after fielding 4595 surveys (29.6% adjusted response rate). In weighted analyses, 36.3% reported HIV-related training. Using adjusted prevalence ratio (aPR) and confidence intervals (CI), we found that PCPs with HIV-related training (compared to those with no training) were more likely to be familiar with nPEP (aPR = 1.32, 95% CI 1.05, 1.67) and PrEP (aPR = 1.67, 95% CI 1.19, 2.38); and to have ever prescribed PrEP to patients (aPR = 1.75, 95% CI 1.10, 2.78). Increased HIV-related trainings among PCPs in high HIV prevalence Southeast jurisdictions may be warranted. Strengthening nPEP and PrEP familiarity among PCPs in Southeast may advance national HIV prevention goals.

Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups. In this multicentre, double-blind, response-adaptive, randomised controlled trial, we recruited patients from 58 hospital emergency departments across the USA. Patients were eligible for inclusion if they were aged 2 years or older, had been treated for a generalised convulsive seizure of longer than 5 min duration with adequate doses of benzodiazepines, and continued to have persistent or recurrent convulsions in the emergency department for at least 5 min and no more than 30 min after the last dose of benzodiazepine. Patients were randomly assigned in a response-adaptive manner, using Bayesian methods and stratified by age group (<18 years, 18–65 years, and >65 years), to levetiracetam, fosphenytoin, or valproate. All patients, investigators, study staff, and pharmacists were masked to treatment allocation. The primary outcome was absence of clinically apparent seizures with improved consciousness and without additional antiseizure medication at 1 h from start of drug infusion. The primary safety outcome was life-threatening hypotension or cardiac arrhythmia. The efficacy and safety outcomes were analysed by intention to treat. This study is registered in ClinicalTrials.gov, NCT01960075. Between Nov 3, 2015, and Dec 29, 2018, we enrolled 478 patients and 462 unique patients were included: 225 children (aged <18 years), 186 adults (18–65 years), and 51 older adults (>65 years). 175 (38%) patients were randomly assigned to levetiracetam, 142 (31%) to fosphenyltoin, and 145 (31%) were to valproate. Baseline characteristics were balanced across treatments within age groups. The primary efficacy outcome was met in those treated with levetiracetam for 52% (95% credible interval 41–62) of children, 44% (33–55) of adults, and 37% (19–59) of older adults; with fosphenytoin in 49% (38–61) of children, 46% (34–59) of adults, and 35% (17–59) of older adults; and with valproate in 52% (41–63) of children, 46% (34–58) of adults, and 47% (25–70) of older adults. No differences were detected in efficacy or primary safety outcome by drug within each age group. With the exception of endotracheal intubation in children, secondary safety outcomes did not significantly differ by drug within each age group. Children, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus. National Institute of Neurological Disorders and Stroke, National Institutes of Health.