Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT).

A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 8 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and 2 clinicians who were representatives of ESMO. The focus of the meeting was exclusively on the intratumoral injection/delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of human intratumoral immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a blurring of the data reported from different studies. The goal was to provide a reference document, endorsed by the panel members that could provide guidance to clinical investigators, pharmaceutical companies, ethics committees, independent review boards, patient advocates and the regulatory authorities and promote an increase in the number and quality of HIT-IT clinical trials in the future. Particular emphasis was placed not only on the development of precise definitions to facilitate a better understanding between investigators but also on the importance of systematic serial biopsies as a driver for translational research and the need for the recording and reporting of data, to facilitate a better understanding of the key processes involved

The Fecal Viral Flora of Wild Rodents

The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat) collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in mammals

Surveillance of Ixodes ricinus ticks (Acari: Ixodidae) in Iceland

Background: Ixodes ricinus is a three-host tick, a principal vector of Borrelia burgdorferi (s.l.) and one of the main vectors of tick-borne encephalitis (TBE) virus. Iceland is located in the North Atlantic Ocean with subpolar oceanic climate. During the past 3–4 decades, average temperature has increased, supporting more favourable conditions for ticks. Reports of I. ricinus have increased in recent years. If these ticks were able to establish in a changing climate, Iceland may face new threats posed by tick-borne diseases. Methods: Active field surveillance by tick flagging was conducted at 111 sites around Iceland from August 2015 to September 2016. Longworth mammal traps were used to trap Apodemus sylvaticus in southwestern and southern Iceland. Surveillance on tick importation by migratory birds was conducted in southeastern Iceland, using bird nets and a Heligoland trap. Vulpes lagopus carcasses from all regions of the country were inspected for ticks. In addition, existing and new passive surveillance data from two institutes have been merged and are presented. Continental probability of presence models were produced. Boosted Regression Trees spatial modelling methods and its predictions were assessed against reported presence. Results: By field sampling 26 questing I. ricinus ticks (7 males, 3 females and 16 nymphs) were collected from vegetation from three locations in southern and southeastern Iceland. Four ticks were found on migratory birds at their arrival in May 2016. A total of 52 A. sylvaticus were live-trapped but no ticks were found nor on 315 V. lagopus carcasses. Passive surveillance data collected since 1976, reports further 214 I. ricinus ticks from 202 records, with an increase of submissions in recent years. The continental probability of presence model correctly predicts approximately 75% of the recorded presences, but fails to predict a fairly specific category of recorded presence in areas where the records are probably opportunistic and not likely to lead to establishment. Conclusions: To the best of our knowledge, this study represents the first finding of questing I. ricinus ticks in Iceland. The species could possibly be established locally in Iceland in low abundance, although no questing larvae have yet been detected to confirm established populations. Submitted tick records have increased recently, which may reflect an increase in exposure, or in interest in ticks. Furthermore, the amount of records on dogs, cats and humans indicate that ticks were acquired locally, presenting a local biting risk. Tick findings on migratory birds highlight a possible route of importation. Obtaining questing larvae is now a priority to confirm that I. ricinus populations are established in Iceland. Further surveys on wild mammals (e.g. Rangifer tarandus), livestock and migratory birds are recommended to better understand their role as potential hosts for I. ricinus.Work was carried out under VectorNet, a European network for sharing data on the geographic distribution of arthropod vectors, transmitting human and animal disease agents (framework contract OC/EFSA/AHAW/2013/02-FWC1) funded by the European Food Safety Authority (EFSA) and the European Centre for Disease prevention and Control (ECDC). JM is also partly funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Environmental Change and Health at the London School of Hygiene & Tropical Medicine in partnership with Public Health England (PHE), and in collaboration with the University of Exeter, University College London, and the Met Office; and partly funded by the NIHR HPRU on Emerging Infections and Zoonoses at the University of Liverpool in partnership with PHE and Liverpool School of Tropical Medicine.Peer Reviewe

The molecular structure of Roesky's sulfoxide - Another computational challenge

The molecular structure of 1-oxo-1,2,4,3,5-trithiadiazole (1) has been studied theoretically by a large number of computational methods. The results of calculations using different DFT functionals are compared with those obtained from HF, MP2, MP4(SDQ), QCISD and CCSD calculations. In addition, the influence of a number of basis sets on the calculated geometry was investigated. The results of the post-HF methods show that improving the level of theory from CCSD to CCSD(T) still has a considerable effect on the geometry. Taking the CCSD/cc-pVTZ geometry as a reference the DFT/B1B95/aug-cc-pVTZ combination appears to provide the most valuable description of all the examined functionals. (c) 2006 Elsevier B.V. All rights reserved.</p

Schatting van de incidentie van de klinische manifestaties van Lyme borreliose in Vlaanderen op basis van primaire surveillancegegevens en een meta-analyse, 2015-2017

Lyme borreliose (LB) is een belangrijke tekenoverdraagbare ziekte die verschillende sympto-men kan veroorzaken waarbij onder andere de huid, het zenuwstelsel of de gewrichten kunnen worden aangetast. Deze studie heeft als doel om de incidentie van de verschillen-de klinische manifestaties van LB in Vlaanderen te schatten. De incidentie van erythema migrans (EM) in Vlaanderen werd via een netwerk van huisartsenpeilpraktijken geschat op 126,0/100 000 inwoners (95% onzekerheidsinterval [OI] 101,1–150,9) voor de periode 2015-2017. Op basis van een systematisch literatuuronderzoek en een meta-analyse werden de verhoudingen van andere manifestaties ten opzichte van EM in de buurlanden van België geschat. De combinatie van deze ratio's met de EM-incidentie in Vlaanderen resulteerde in een incidentieschatting van 3,1/100 000 inwoners (95% OI 1,8–4,9) voor Lyme neuroborre-liose, 2,7/100 000 (95% OI 2,1–3,4) voor Lyme artritis en 1,8/100 000 (95% OI 1,3–2,3) voor andere minder frequente manifestaties. Gegevens over de incidentie van alle klinische manifestaties van LB, inclusief de meer zeldzame maar vaak ernstigere manifestaties, zijn belangrijk wanneer men de ziektelast of economische kost van de ziekte wil bepalen. De eigenschappen van de surveillancesystemen in België en de verschillende buurlanden kun-nen aanleiding gegeven hebben tot zowel over- als onderschatting van de verschillende manifestaties en toekomstige studies om deze resultaten te valideren zijn belangrijk

Five-membered arsenic-sulfur-nitrogen heterocycles, RAs(S2N2) (R = Me, Et, iPr, tBu, Ph, Mes)

This work was carried out with the financial support of Engineering and Physical Sciences Research Council (EPSRC), U.K.A series of 5-alkyl/aryl-1,3 lambda(4)delta(2),2,4,5-dithiadiazarsoles RAs(S2N2) (R = Me, Et, Pr-i, Bu-t, Ph, Mes) were prepared by a ligand exchange between [(Bu2Sn)-Bu-n(S2N2)](2) and the corresponding organodihalogenoarsines RAsX2 (X = Cl, I). All products were characterized by NMR, IR, and Raman spectroscopies and mass spectrometry. The crystal structures of the aryldithiadiazarsoles (R = Ph, Mes) were determined.PostprintPeer reviewe