An Antimethanogenic Nutritional Intervention in Early Life of Ruminants Modifies Ruminal Colonization by Archaea

The aim of this work was to study whether feeding a methanogen inhibitor from birth of goat kids and their does has an impact on the archaeal population colonizing the rumen and to what extent the impact persists later in life. Sixteen goats giving birth to two kids were used. Eight does were treated (D+) with bromochloromethane after giving birth and over 2 months. The other 8 goats were not treated (D−). One kid per doe in both groups was treated with bromochloromethane (k+) for 3 months while the other was untreated (k−), resulting in four experimental groups: D+/k+, D+/k−, D−/k+, and D−/k−. Rumen samples were collected from kids at weaning and 1 and 4 months after (3 and 6 months after birth) and from does at the end of the treating period (2 months). Pyrosequencing analyses showed a modified archaeal community composition colonizing the rumen of kids, although such effect did not persist entirely 4 months after; however, some less abundant groups remained different in treated and control animals. The different response on the archaeal community composition observed between offspring and adult goats suggests that the competition occurring in the developing rumen to occupy different niches offer potential for intervention

Analysis of the rumen microbiome and metabolome to study the effect of an antimethanogenic treatment applied in early life of kid goats

This work aimed to gain insight into the transition from milk to solid feeding at weaning combining genomics and metabolomics on rumen contents from goat kids treated with a methanogenic inhibitor (bromochloromethane, BCM). Sixteen goats giving birth to two kids were used. Eight does were treated (D+) with BCM after giving birth and over 2 months. One kid per doe in both groups was treated with BCM (k+) for 3 months while the other was untreated (k–). Rumen samples were collected from kids at weaning (W) and 1 (W + 1) and 4 (W + 4) months after and from does at weaning and subjected to 16S pyrosequencing and metabolomics analyses combining GC/LC-MS. Results from pyrosequencing showed a clear effect of age of kids, with more diverse bacterial community as solid feed becomes more important after weaning. A number of specific OTUs were significantly different as a result of BCM treatment of the kid at W while at W + 1 and W + 4 less OTUs were significantly changed. At W + 1, Prevotella was increased and Butyrivibrio decreased in BCM treated kids. At W + 4 only the effect of treating mothers resulted in significant changes in the abundance of some OTUs: Ruminococcus, Butyrivibrio and Prevotella. The analysis of the OTUs shared by different treatments revealed that kids at weaning had the largest number of unique OTUs compared with kids at W + 1 (137), W + 4 (238), and does (D) (23). D + k+ kids consistently shared more OTUs with mothers than the other three groups at the three sampling times. The metalobomic study identified 473 different metabolites. In does, lipid super pathway included the highest number of metabolites that were modified by BCM, while in kids all super-pathways were evenly affected. The metabolomic profile of samples from kids at W was different in composition as compared to W + 1 and W + 4, which may be directly ascribed to the process of rumen maturation and changes in the solid diet. This study shows the complexity of the bacterial community and metabolome in the rumen before weaning, which clearly differ from that after weaning and highlight the importance of the dam in transmitting the primary bacterial community after birth.</p

Use of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer: a multidisciplinary perspective for daily practice

Background: Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; and a good relationship between the specialist, patients, and caregivers. Methods: With the aim of providing suggestions that can be useful in ev eryday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiat ed thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events. Conclusions: It is essential to provide guidance for the management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. Whil e the therapeutic landscape in RAI-R DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as the management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed

SELIMETRY- a multicentre I-131 dosimetry trial: a clinical perspective

Treatment options for patients with thyroid cancer that is no longer sensitive to iodine therapy are limited. Those treatments which currently exist are associated with significant toxicity. The SELIMETRY trial (EudraCT No 2015-002269-47) aims to investigate the role of the MEK inhibitor Selumetinib in resensitizing advanced iodine refractory differentiated thyroid cancer to radioiodine therapy. Patients deemed to have sufficient iodine uptake in previously iodine refractory lesions after 4 weeks of Selumetinib therapy will be given an empirical activity of 5.5 GBq I-131, and response to therapy will be assessed. The trial presents an opportunity to investigate the dosimetric aspects of radioiodine therapy for advanced thyroid cancer. Patients will undergo serial I-123 single-photon emission CT (SPECT)/CT scans following Selumetinib therapy to determine whether there has been a change in the degree of iodine uptake to justify further I-131 therapy, and to allow dosimetric calculations to predict absorbed dose to target lesions following therapy. Patients receiving I-131 therapy will undergo a further series of post-therapy SPECT/CT scans to allow dosimetric calculations. We describe the challenges in setting up a multicentre trial in a relatively underinvestigated field, describing the work that has been carried out to calibrate and validate measurements to ensure that standardized image data are collected at each site. We hope that this trial will lead to individualization and optimization of therapy for patients with advanced thyroid cancer and that the ground work carried out in setting up a network of centres capable of standardized molecular radiotherapy dosimetry will lead to further clinical trials in this field

An Antimethanogenic Nutritional Intervention in Early Life of Ruminants Modifies Ruminal Colonization by Archaea

The aim of this work was to study whether feeding a methanogen inhibitor from birth of goat kids and their does has an impact on the archaeal population colonizing the rumen and to what extent the impact persists later in life. Sixteen goats giving birth to two kids were used. Eight does were treated (D+) with bromochloromethane after giving birth and over 2 months. The other 8 goats were not treated (D−). One kid per doe in both groups was treated with bromochloromethane (k+) for 3 months while the other was untreated (k−), resulting in four experimental groups: D+/k+, D+/k−, D−/k+, and D−/k−. Rumen samples were collected from kids at weaning and 1 and 4 months after (3 and 6 months after birth) and from does at the end of the treating period (2 months). Pyrosequencing analyses showed a modified archaeal community composition colonizing the rumen of kids, although such effect did not persist entirely 4 months after; however, some less abundant groups remained different in treated and control animals. The different response on the archaeal community composition observed between offspring and adult goats suggests that the competition occurring in the developing rumen to occupy different niches offer potential for intervention

ORCC UKRN Primer on Working in Research Data Management

This is an introductory guide for those working and considering working in the area of research data management. It was drafted by members of the Open Research Competencies Coalition. Research Data Management (RDM) refers to the storage, access, and preservation of data produced by a given investigation. Data management practices cover the entire lifecycle of a project, from planning the investigation, conducting it, backing up data as it is created and used, to long term preservation of data deliverables after the research investigation has concluded

ORCC UKRN Primer on Working in Open Research

This is an introductory guide for those working and considering working in the area of open research. It was drafted by members of the Open Research Competencies Coalition. There are many resources available on the topic of open research either aimed at those working in open research roles or more generally on open research practices. A list is included in the document

Population structure and history of the Welsh sheep breeds determined by whole genome genotyping

BACKGROUND: One of the most economically important areas within the Welsh agricultural sector is sheep farming, contributing around £230 million to the UK economy annually. Phenotypic selection over several centuries has generated a number of native sheep breeds, which are presumably adapted to the diverse and challenging landscape of Wales. Little is known about the history, genetic diversity and relationships of these breeds with other European breeds. We genotyped 353 individuals from 18 native Welsh sheep breeds using the Illumina OvineSNP50 array and characterised the genetic structure of these breeds. Our genotyping data were then combined with, and compared to, those from a set of 74 worldwide breeds, previously collected during the International Sheep Genome Consortium HapMap project. RESULTS: Model based clustering of the Welsh and European breeds indicated shared ancestry. This finding was supported by multidimensional scaling analysis (MDS), which revealed separation of the European, African and Asian breeds. As expected, the commercial Texel and Merino breeds appeared to have extensive co-ancestry with most European breeds. Consistently high levels of haplotype sharing were observed between native Welsh and other European breeds. The Welsh breeds did not, however, form a genetically homogeneous group, with pairwise F(ST) between breeds averaging 0.107 and ranging between 0.020 and 0.201. Four subpopulations were identified within the 18 native breeds, with high homogeneity observed amongst the majority of mountain breeds. Recent effective population sizes estimated from linkage disequilibrium ranged from 88 to 825. CONCLUSIONS: Welsh breeds are highly diverse with low to moderate effective population sizes and form at least four distinct genetic groups. Our data suggest common ancestry between the native Welsh and European breeds. These findings provide the basis for future genome-wide association studies and a first step towards developing genomics assisted breeding strategies in the UK. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-015-0216-x) contains supplementary material, which is available to authorized users