Intermittent bulk release of human cytomegalovirus

Human Cytomegalovirus (HCMV) can infect a variety of cell types by using virions of varying glycoprotein compositions. It is still unclear how this diversity is generated, but spatio-temporally separated envelopment and egress pathways might play a role. So far, one egress pathway has been described in which HCMV particles are individually enveloped into small vesicles and are subsequently exocytosed continuously. However, some studies have also found enveloped virus particles inside multivesicular structures but could not link them to productive egress or degradation pathways. We used a novel 3D-CLEM workflow allowing us to investigate these structures in HCMV morphogenesis and egress at high spatio-temporal resolution. We found that multiple envelopment events occurred at individual vesicles leading to multiviral bodies (MViBs), which subsequently traversed the cytoplasm to release virions as intermittent bulk pulses at the plasma membrane to form extracellular virus accumulations (EVAs). Our data support the existence of a novel bona fide HCMV egress pathway, which opens the gate to evaluate divergent egress pathways in generating virion diversity

Integrated Electro-Optic Isolator on Thin Film Lithium Niobate

Optical isolator is an indispensable component of almost any optical system and is used to protect a laser from unwanted reflections for phase-stable coherent operation. The development of chip-scale optical systems, powered by semiconductor lasers integrated on the same chip, has resulted in a need for a fully integrated optical isolator. However, conventional approaches based on application of magneto-optic materials to break the reciprocity and provide required isolation have significant challenges in terms of material processing and insertion loss. As a result, many magnetic-free approaches have been explored, including acousto-optics, optical nonlinearity, and electro-optics. However, to date, the realization of an integrated isolator with low insertion loss, high isolation ratio, broad bandwidth, and low power consumption on a monolithic material platform is still absent. Here we realize non-reciprocal traveling-wave EO-based isolator on thin-film LN, enabling maximum optical isolation of 48 dB and an on-chip insertion loss of 0.5 dB using a single-frequency microwave drive at 21-dBm RF power. The isolation ratio is verified to be larger than 37 dB across a tunable optical wavelength range from 1510 to 1630 nm. We verify that our hybrid DFB laser - LN isolator module successfully protects the single-mode operation and the linewidth of the DFB laser from reflection. Our result is a significant step towards a practical high-performance optical isolator on chip

The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics

In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”. The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept

Mauritius since the last glacial:environmental and climatic reconstruction of the last 38 000 years from Kanaka Crater

A 10 m long peat core from the Kanaka Crater (20° 25′ S, 57° 31′ E), located at 560 m elevation in Mauritius, was analyzed for microfossils. Eight radiocarbon ages show the pollen record reflects environmental and climatic change of the last ca. 38 cal ka BP. The record shows that the island was continuously covered by forest with Erica heath (Philippia) in the uplands. Cyperaceous reedswamp with Pandanus trees was abundant in the coastal lowlands as well as locally in the waterlogged crater. The record shows changes in climatic humidity (wet from 38.0 to 22.7 cal ka BP, drier from 22.7 to 10.6 cal ka BP, and wetter again from 10.6 cal ka BP to recent) as the main response to climate change. A high turnover in montane forest species is evidenced at 22.7 cal ka BP and at the start of the Holocene. The limited altitudinal ranges in the mountains of Mauritius (maximum altitude 828 m), and changing humidity being more important than changing temperature, suggests that in response to climate change a reassortment in taxonomic composition of montane forests might be equally important as displacement of forest types to new altitudinal intervals. We found weak impact of the latitudinal migration of the Intertropical Convergence Zone and data suggest that the Indian Ocean Dipole is a more important driver for climatic change in the southwest Indian Ocean

Gamma-Ray Studies of Blazars: Synchro-Compton Analysis of Flat Spectrum Radio Quasars

We extend a method for modeling synchrotron and synchrotron self-Compton radiations in blazar jets to include external Compton processes. The basic model assumption is that the blazar radio through soft X-ray flux is nonthermal synchrotron radiation emitted by isotropically-distributed electrons in the randomly directed magnetic field of outflowing relativistic blazar jet plasma. Thus the electron distribution is given by the synchrotron spectrum, depending only on the Doppler factor $\delta_{\rm D}$ and mean magnetic field $B$, given that the comoving emission region size scale R_b^\prime \lesssim c \dD t_v/(1+z), where $t_v$ is variability time and $z$ is source redshift. Generalizing the approach of Georganopoulos, Kirk, and Mastichiadis (2001) to arbitrary anisotropic target radiation fields, we use the electron spectrum implied by the synchrotron component to derive accurate Compton-scattered $\gamma$-ray spectra throughout the Thomson and Klein-Nishina regimes for external Compton scattering processes. We derive and calculate accurate $\gamma$-ray spectra produced by relativistic electrons that Compton-scatter (i) a point source of radiation located radially behind the jet, (ii) photons from a thermal Shakura-Sunyaev accretion disk and (iii) target photons from the central source scattered by a spherically-symmetric shell of broad line region (BLR) gas. Calculations of broadband spectral energy distributions from the radio through $\gamma$-ray regimes are presented, which include self-consistent $\gamma\gamma$ absorption on the same radiation fields that provide target photons for Compton scattering. Application of this baseline flat spectrum radio/$\gamma$-ray quasar model is considered in view of data from $\gamma$-ray telescopes and contemporaneous multi-wavelength campaigns.Comment: Accepted by ApJ. 22 pages, 12 figures, 2 tables. Minor revisions to figures and tex

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe"

Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10 years. We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID. At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38-63%) in 10 years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12-24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18-79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10 years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5-17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20-80%. The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe. Measuring the amount of HCV in the population of PWID is uncertain. To reduce HCV infection to minimal levels in Europe will require scale-up of both HCV treatment and other interventions that reduce injecting risk (especially OST and provision of sterile injecting equipment

RESPONDER – diagnosis of pathological complete response by vacuum-assisted biopsy after neoadjuvant chemotherapy in breast Cancer - a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial

Background: Neoadjuvant chemotherapy (NACT) is a standard approach of the multidisciplinary treatment of breast cancer. Depending on the biological subtype a pathological complete response in the breast (bpCR) can be achieved in up to 60% of the patients. However, only limited accuracy can be reached when using imaging for prediction of bpCR prior to surgery. Due to this diagnostic uncertainty, surgery after NACT is considered to be obligatory for all patients in order to either completely remove residual disease or to diagnose a bpCR histologically. The purpose of this trial is to evaluate the accuracy of a vacuum-assisted biopsy (VAB) to diagnose a bpCR after NACT prior to surgery. Methods: This study is a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial. The study will take place at 21 trial sites in Germany. Six hundred female patients with breast cancer after completed NACT showing at least a partial response to NACT treatment will be enrolled. A vacuum-assisted biopsy (VAB) guided either by ultrasound or mammography will be performed followed by histopathological evaluation of the VAB specimen before standard, guideline-adherent breast surgery. The study is designed to prove that the false negative rate of the VAB is below 10%. Discussion: As a bpCR is becoming a more frequent result after NACT, the question arises whether breast surgery is therapeutically necessary in such cases. To study this subject further, it will be crucial to develop a reliable test to diagnose a bpCR without surgery. During the study we anticipate possible problems in patient recruitment as the VAB intervention does not provide participating patients with any personal benefit. Hence, a proficient informed consent discussion with the patient and a detailed explanation of the study aim will be crucial for patient recruitment. Another critical issue is the histopathological VAB evaluation of a non-tumorous specimen as this may have been taken either from the former tumor region (bpCR) or outside of the (former) tumor region (non-representative VAB, sampling error). Trial registration: The trial has been registered at clinicaltrials.gov with the identifier NCT02948764 on October 28, 2016 and at the German Clinical Trials Register ( DRKS00011761 ) on February 20, 2017. The date of enrolment of the first participant to the trial was on March 8, 2017

The Canadian Chronic Disease Surveillance System: A model for collaborative surveillance

Chronic diseases have a major impact on populations and healthcare systems worldwide. Administrative health data are an ideal resource for chronic disease surveillance because they are population-based and routinely collected. For multi-jurisdictional surveillance, a distributed model is advantageous because it does not require individual-level data to be shared across jurisdictional boundaries. Our objective is to describe the process, structure, benefits, and challenges of a distributed model for chronic disease surveillance across all Canadian provinces and territories (P/Ts) using linked administrative data. The Public Health Agency of Canada (PHAC) established the Canadian Chronic Disease Surveillance System (CCDSS) in 2009 to facilitate standardized, national estimates of chronic disease prevalence, incidence, and outcomes. The CCDSS primarily relies on linked health insurance registration files, physician billing claims, and hospital discharge abstracts. Standardized case definitions and common analytic protocols are applied to the data for each P/T; aggregate data are shared with PHAC and summarized for reports and open access data initiatives. Advantages of this distributed model include: it uses the rich data resources available in all P/Ts; it supports chronic disease surveillance capacity building in all P/Ts; and changes in surveillance methodology can be easily developed by PHAC and implemented by the P/Ts. However, there are challenges: heterogeneity in administrative databases across jurisdictions and changes in data quality over time threaten the production of standardized disease estimates; a limited set of databases are common to all P/Ts, which hinders potential CCDSS expansion; and there is a need to balance comprehensive reporting with P/T disclosure requirements to protect privacy. The CCDSS distributed model for chronic disease surveillance has been successfully implemented and sustained by PHAC and its P/T partners. Many lessons have been learned about national surveillance involving jurisdictions that are heterogeneous with respect to healthcare databases, expertise and analytical capacity, population characteristics, and priorities

Building consensus around the assessment and interpretation of Symbiodiniaceae diversity

Within microeukaryotes, genetic variation and functional variation sometimes accumulate more quickly than morphological differences. To understand the evolutionary history and ecology of such lineages, it is key to examine diversity at multiple levels of organization. In the dinoflagellate family Symbiodiniaceae, which can form endosymbioses with cnidarians (e.g., corals, octocorals, sea anemones, jellyfish), other marine invertebrates (e.g., sponges, molluscs, flatworms), and protists (e.g., foraminifera), molecular data have been used extensively over the past three decades to describe phenotypes and to make evolutionary and ecological inferences. Despite advances in Symbiodiniaceae genomics, a lack of consensus among researchers with respect to interpreting genetic data has slowed progress in the field and acted as a barrier to reconciling observations. Here, we identify key challenges regarding the assessment and interpretation of Symbiodiniaceae genetic diversity across three levels: species, populations, and communities. We summarize areas of agreement and highlight techniques and approaches that are broadly accepted. In areas where debate remains, we identify unresolved issues and discuss technologies and approaches that can help to fill knowledge gaps related to genetic and phenotypic diversity. We also discuss ways to stimulate progress, in particular by fostering a more inclusive and collaborative research community. We hope that this perspective will inspire and accelerate coral reef science by serving as a resource to those designing experiments, publishing research, and applying for funding related to Symbiodiniaceae and their symbiotic partnerships.journal articl