International travel between global urban centres vulnerable to yellow fever transmission.

OBJECTIVE: To examine the potential for international travel to spread yellow fever virus to cities around the world. METHODS: We obtained data on the international flight itineraries of travellers who departed yellow fever-endemic areas of the world in 2016 for cities either where yellow fever was endemic or which were suitable for viral transmission. Using a global ecological model of dengue virus transmission, we predicted the suitability of cities in non-endemic areas for yellow fever transmission. We obtained information on national entry requirements for yellow fever vaccination at travellers' destination cities. FINDINGS: In 2016, 45.2 million international air travellers departed from yellow fever-endemic areas of the world. Of 11.7 million travellers with destinations in 472 cities where yellow fever was not endemic but which were suitable for virus transmission, 7.7 million (65.7%) were not required to provide proof of vaccination upon arrival. Brazil, China, India, Mexico, Peru and the United States of America had the highest volumes of travellers arriving from yellow fever-endemic areas and the largest populations living in cities suitable for yellow fever transmission. CONCLUSION: Each year millions of travellers depart from yellow fever-endemic areas of the world for cities in non-endemic areas that appear suitable for viral transmission without having to provide proof of vaccination. Rapid global changes in human mobility and urbanization make it vital for countries to re-examine their vaccination policies and practices to prevent urban yellow fever epidemics

Naturally occurring diacetyl and 2,3-pentanedione concentrations associated with roasting and grinding unflavored coffee beans in a commercial setting

AbstractOver the last decade, concerns have been raised about potential respiratory health effects associated with occupational exposure to the flavoring additives diacetyl and 2,3-pentanedione. Both of these diketones are also natural components of many foods and beverages, including roasted coffee. To date, there are no published studies characterizing workplace exposures to these diketones during commercial roasting and grinding of unflavored coffee beans. In this study, we measured naturally occurring diacetyl, 2,3-pentanedione, and respirable dust at a facility that roasts and grinds coffee beans with no added flavoring agents. Sampling was conducted over the course of three roasting batches and three grinding batches at varying distances from a commercial roaster and grinder. The three batches consisted of lightly roasted soft beans, lightly roasted hard beans, and dark roasted hard beans. Roasting occurred for 37 to 41min, and the grinding process took between 8 and 11min. Diacetyl, 2,3-pentanedione, and respirable dust concentrations measured during roasting ranged from less than the limit of detection (<LOD) to 0.0039ppm, <LOD to 0.018ppm, and <LOD to 0.31mg/m3, respectively. During grinding, diacetyl, 2,3-pentanedione, and respirable dust concentrations ranged from 0.018 to 0.39ppm, 0.0089 to 0.21ppm, and <LOD to 1.7mg/m3, respectively. For any given bean/roast combination and sample location, diketone concentrations during grinding were higher than those measured during roasting. During grinding, concentrations decreased with increased distance from the source. Measured concentrations of both diketones were higher during grinding of soft beans than hard beans. The results indicate that airborne concentrations of naturally occurring diacetyl and 2,3-pentanedione associated with unflavored coffee processing: (1) are similar to the concentrations that have been measured in food flavoring facilities; (2) are likely to exceed some recommended short-term occupational exposure limits, but; (3) based on previous analyses of exposure response relationships in animal studies, are far below the concentrations that are expected to cause even minimal responses in the human respiratory tract

Finishing a whole-genome shotgun: Release 3 of the Drosophila melanogaster euchromatic genome sequence

BACKGROUND: The Drosophila melanogaster genome was the first metazoan genome to have been sequenced by the whole-genome shotgun (WGS) method. Two issues relating to this achievement were widely debated in the genomics community: how correct is the sequence with respect to base-pair (bp) accuracy and frequency of assembly errors? And, how difficult is it to bring a WGS sequence to the accepted standard for finished sequence? We are now in a position to answer these questions. RESULTS: Our finishing process was designed to close gaps, improve sequence quality and validate the assembly. Sequence traces derived from the WGS and draft sequencing of individual bacterial artificial chromosomes (BACs) were assembled into BAC-sized segments. These segments were brought to high quality, and then joined to constitute the sequence of each chromosome arm. Overall assembly was verified by comparison to a physical map of fingerprinted BAC clones. In the current version of the 116.9 Mb euchromatic genome, called Release 3, the six euchromatic chromosome arms are represented by 13 scaffolds with a total of 37 sequence gaps. We compared Release 3 to Release 2; in autosomal regions of unique sequence, the error rate of Release 2 was one in 20,000 bp. CONCLUSIONS: The WGS strategy can efficiently produce a high-quality sequence of a metazoan genome while generating the reagents required for sequence finishing. However, the initial method of repeat assembly was flawed. The sequence we report here, Release 3, is a reliable resource for molecular genetic experimentation and computational analysis

Management of toxic ingestions with the use of renal replacement therapy

Although rare, renal replacement therapy (RRT) for the treatment of the metabolic, respiratory and hemodynamic complications of intoxications may be required. Understanding the natural clearance of the medications along with their volume of distribution, protein binding and molecular weight will help in understanding the benefit of commencing RRT. This information will aid in choosing the optimal forms of RRT in an urgent setting. Overdose of common pediatric medications are discussed with suggestions on the type of RRT within this educational review

Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study

Background Cyclin-dependent kinases (CDK) 4 and 6 regulate G1 to S cell cycle progression and are often altered in cancers. Abemaciclib is a selective inhibitor of CDK4 and CDK6 approved for administration on a continuous dosing schedule as monotherapy or as combination therapy with an aromatase inhibitor or fulvestrant in patients with advanced or metastatic breast cancer. This Phase 1b study evaluated the safety and tolerability, pharmacokinetics, and antitumor activity of abemaciclib in combination with endocrine therapy for metastatic breast cancer (MBC), including aromatase inhibitors (letrozole, anastrozole, or exemestane) or tamoxifen. Patients and Methods Women ≥18 years old with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) MBC were eligible for enrollment. Eligibility included measurable disease or non-measurable but evaluable bone disease by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, Eastern Cooperative Oncology Group performance status 0–1, and no prior chemotherapy for metastatic disease. Adverse events were graded by the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 and tumor response were assessed by RECIST v1.1. Results Sixty-seven patients were enrolled and received abemaciclib 200 mg every 12 hours in combination with letrozole (Part A, n=20), anastrozole (Part B, n=16), tamoxifen (Part C, n=16), or exemestane (Part D, n=15). The most common treatment-emergent adverse events (TEAE) were diarrhea, fatigue, nausea, and abdominal pain. Grade 4 TEAEs were reported in five patients (one each with hyperglycemia, hypertension, neutropenia, procedural hemorrhage, and sepsis). There was no effect of abemaciclib or endocrine therapy on the pharmacokinetics of any combination study drug. Across all treated patients, the median progression-free survival was 25.4 months (95% confidence interval: 18.0, 35.8). The objective response rate was 38.9% in 36 patients with measurable disease. Conclusions Abemaciclib in combination with multiple endocrine therapy options exhibited manageable safety and promising antitumor activity in patients with HR+, HER2- MBC. Clinical Trial Registration https://clinicaltrials.gov/, identifier NCT0205713

Brown marmorated stink bug, Halyomorpha halys (Stål), genome: putative underpinnings of polyphagy, insecticide resistance potential and biology of a top worldwide pest

Background Halyomorpha halys (Stål), the brown marmorated stink bug, is a highly invasive insect species due in part to its exceptionally high levels of polyphagy. This species is also a nuisance due to overwintering in human-made structures. It has caused significant agricultural losses in recent years along the Atlantic seaboard of North America and in continental Europe. Genomic resources will assist with determining the molecular basis for this species’ feeding and habitat traits, defining potential targets for pest management strategies. Results Analysis of the 1.15-Gb draft genome assembly has identified a wide variety of genetic elements underpinning the biological characteristics of this formidable pest species, encompassing the roles of sensory functions, digestion, immunity, detoxification and development, all of which likely support H. halys’ capacity for invasiveness. Many of the genes identified herein have potential for biomolecular pesticide applications. Conclusions Availability of the H. halys genome sequence will be useful for the development of environmentally friendly biomolecular pesticides to be applied in concert with more traditional, synthetic chemical-based controls

Genomic and epidemiological characterisation of a dengue virus outbreak among blood donors in Brazil.

Outbreaks caused by Dengue, Zika and Chikungunya viruses can spread rapidly in immunologically naïve populations. By analysing 92 newly generated viral genome sequences from blood donors and recipients, we assess the dynamics of dengue virus serotype 4 during the 2012 outbreak in Rio de Janeiro. Phylogenetic analysis indicates that the outbreak was caused by genotype II, although two isolates of genotype I were also detected for the first time in Rio de Janeiro. Evolutionary analysis and modelling estimates are congruent, indicating a reproduction number above 1 between January and June, and at least two thirds of infections being unnoticed. Modelling analysis suggests that viral transmission started in early January, which is consistent with multiple introductions, most likely from the northern states of Brazil, and with an increase in within-country air travel to Rio de Janeiro. The combination of genetic and epidemiological data from blood donor banks may be useful to anticipate epidemic spread of arboviruses