H2O maser emission from bright rimmed clouds in the southern hemisphere

Water maser emission is a powerful tracer of the presence of embedded sources in dense clouds since it requires elevated temperatures (>100 K) and densities (>107 cm−3) that can be found in circumstellar disks and/or jets/outflows associated with Young Stellar Objects. Bright rimmed clouds compressed by ionization fronts from nearby massive stars are considered good examples of externally triggered star formation, possibly resulting in the formation of massive stars. Aims. We aim to determine the water maser emission frequency and characteristics of 45 bright rimmed clouds in the southern hemisphere identified by Sugitani & Ogura (1994, ApJS, 92, 163). Methods. We have used the Tidbinbilla 70-m radiotelescope to perform a high sensitivity survey at 22.2 GHz of the maser emission from the 616−523 rotational transition of H2O molecules. Results. We found 7 water maser sources out of 44 (16% detection rate), 5 being new detections. With the exception of the maser associated with BRC 68, all the other maser are characterized by low integrated fluxes and luminosities. Conclusions. Most maser sources fall below the correlation between the H2O and far-infrared luminosity found in other studies towards a variety of star forming regions. These results are similar to those found in the companion survey of BRCs in the northern hemisphere by Valdettaro et al. (2005, A&A, 443, 535). The low detection frequency and the properties of water maser emission from BRCs indicate that low-mass star formation is the most natural outcome of the external compression induced by the ionization front from nearby massive stars

Emerging Approaches and Issues in Regulation and Governance of Infrastructure Based Services

The fragmented, complex, and disconnected nature of arrangements within and between infrastructure sectors, along with increasing interdependence between sectors, is reshaping business models of infrastructure based services, prompting the emergence of new approaches to regulation and governance. Drawing on research experience in several infrastructure sectors and reflecting upon a series of workshops, the discussion focuses on emerging issues for the regulation and governance of infrastructure based services. A series of observations from across UK infrastructure are presented, and discussed within an international context. Three emerging areas of change in infrastructure delivery are highlighted: 1) a shift from asset-focused to service-focused delivery, 2) increased cross-sector interaction and 3) changing relationships with(in) the supply chain. The presented argument is that while regulatory changes are gradually pushing the boundaries of existing arrangements, infrastructure governance has seen more extensive changes through the introduction of more and non-traditional actors; and platforms and means for coordination between (public and private) actors. The shift in focus to infrastructure service provision supports the case for improved cross-sector co-ordination, recognising infrastructure services as a bundled consumer good, and address challenges that are common across sectors, such as climate change. Digital platforms provide opportunities to engage directly with consumers and understand the aggregate value and impacts of bundled infrastructure services. Across sectors, there are opportunities and requirements for closer, more open and responsive relationships between infrastructure providers and regulators, which challenge existing imperatives for regulatory independence and certainty. Focusing on infrastructure provision, policy-making and regulation in the UK and internationally, we bring to light recent innovations, tensions and opportunities for the future of infrastructure provision in the UK

The evolution of nutritional care in children and young people with acute lymphoblastic leukaemia: a narrative review

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: Data sharing is not applicable to this article as no new data were created or analysed in this study.Background: Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy in the world. Advances in treatment protocols have resulted in survival rates of >80% in most high‐income countries (HIC); however, children and young people (CYP) with ALL continue to face significant nutrition‐related challenges during treatment. Methods: This narrative review outlines the changing landscape of treatment and survivorship for CYP with ALL and the advances in nutrition knowledge that call for changes to clinical nutrition practice. Results: The incidence of ALL has remained stable in HIC; however, there have been significant advances in survival over the past 30 years. Overweight and obesity are increasingly prevalent in CYP with ALL at diagnosis, during treatment and in survivorship. Coupled with poor diet quality, high‐energy and saturated fat intakes, altered eating behaviours and inactivity, this necessitates the need for a shift in nutrition intervention. Undernutrition remains a concern for CYP with high‐risk treatment protocols where oral or enteral nutrition support remains a cornerstone of maintaining nutrition status. Conclusions: With improved treatment protocols and high survival rates, a shift to focusing on diet quality, prevention of excessive weight gain and obesity during treatment and survivorship is necessary

Autofix for backward-fit sidechains: using MolProbity and real-space refinement to put misfits in their place

Misfit sidechains in protein crystal structures are a stumbling block in using those structures to direct further scientific inference. Problems due to surface disorder and poor electron density are very difficult to address, but a large class of systematic errors are quite common even in well-ordered regions, resulting in sidechains fit backwards into local density in predictable ways. The MolProbity web site is effective at diagnosing such errors, and can perform reliable automated correction of a few special cases such as 180° flips of Asn or Gln sidechain amides, using all-atom contacts and H-bond networks. However, most at-risk residues involve tetrahedral geometry, and their valid correction requires rigorous evaluation of sidechain movement and sometimes backbone shift. The current work extends the benefits of robust automated correction to more sidechain types. The Autofix method identifies candidate systematic, flipped-over errors in Leu, Thr, Val, and Arg using MolProbity quality statistics, proposes a corrected position using real-space refinement with rotamer selection in Coot, and accepts or rejects the correction based on improvement in MolProbity criteria and on χ angle change. Criteria are chosen conservatively, after examining many individual results, to ensure valid correction. To test this method, Autofix was run and analyzed for 945 representative PDB files and on the 50S ribosomal subunit of file 1YHQ. Over 40% of Leu, Val, and Thr outliers and 15% of Arg outliers were successfully corrected, resulting in a total of 3,679 corrected sidechains, or 4 per structure on average. Summary Sentences: A common class of misfit sidechains in protein crystal structures is due to systematic errors that place the sidechain backwards into the local electron density. A fully automated method called “Autofix” identifies such errors for Leu, Val, Thr, and Arg and corrects over one third of them, using MolProbity validation criteria and Coot real-space refinement of rotamers

RNA Oxidation Adducts 8-OHG and 8-OHA Change with Aβ42 Levels in Late-Stage Alzheimer's Disease

While research supports amyloid-β (Aβ) as the etiologic agent of Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adducts by gas chromatography/mass spectroscopy across five brain regions from AD cases and age-matched controls. We then used a reductive directed analysis to compare the RNA adducts to common indices of AD neuropathology and various pools of Aβ. Using data from four disease-affected brain regions (Brodmann's Area 9, hippocampus, inferior parietal lobule, and the superior and middle temporal gyri), we found that the RNA adduct 8-hydroxyguanine (8-OHG) decreased, while 8-hydroxyadenine (8-OHA) increased in AD. The cerebellum, which is generally spared in AD, did not show disease related changes, and no RNA adducts correlated with the number of plaques or tangles. Multiple regression analysis revealed that SDS-soluble Aβ42 was the best predictor of changes in 8-OHG, while formic acid-soluble Aβ42 was the best predictor of changes in 8-OHA. This study indicates that although there is a connection between AD related neuropathology and RNA oxidation, this relationship is not straightforward

Multicomponent non-pharmacological intervention to prevent delirium for hospitalised people with advanced cancer: Study protocol for a phase II cluster randomised controlled trial

© 2019 Author(s) (or their employer(s)). Introduction Delirium is a significant medical complication for hospitalised patients. Up to one-third of delirium episodes are preventable in older inpatients through non-pharmacological strategies that support essential human needs, such as physical and cognitive activity, sleep, hydration, vision and hearing. We hypothesised that a multicomponent intervention similarly may decrease delirium incidence, and/or its duration and severity, in inpatients with advanced cancer. Prior to a phase III trial, we aimed to determine if a multicomponent non-pharmacological delirium prevention intervention is feasible and acceptable for this specific inpatient group. Methods and analysis The study is a phase II cluster randomised wait-listed controlled trial involving inpatients with advanced cancer at four Australian palliative care inpatient units. Intervention sites will introduce delirium screening, diagnostic assessment and a multicomponent delirium prevention intervention with six domains of care: preserving natural sleep; maintaining optimal vision and hearing; optimising hydration; promoting communication, orientation and cognition; optimising mobility; and promoting family partnership. Interdisciplinary teams will tailor intervention delivery to each site and to patient need. Control sites will first introduce only delirium screening and diagnosis, later implementing the intervention, modified according to initial results. The primary outcome is adherence to the intervention during the first seven days of admission, measured for 40 consecutively admitted eligible patients. Secondary outcomes relate to fidelity and feasibility, acceptability and sustainability of the study intervention, processes and measures in this patient population, using quantitative and qualitative measures. Delirium incidence and severity will be measured to inform power calculations for a future phase III trial. Ethics and dissemination Ethical approval was obtained for all four sites. Trial results, qualitative substudy findings and implementation of the intervention will be submitted for publication in peer-reviewed journals, and reported at conferences, to study sites and key peak bodies

The Songbird Neurogenomics (SoNG) Initiative: Community-based tools and strategies for study of brain gene function and evolution

BACKGROUND: Songbirds hold great promise for biomedical, environmental and evolutionary research. A complete draft sequence of the zebra finch genome is imminent, yet a need remains for application of genomic resources within a research community traditionally focused on ethology and neurobiological methods. In response, we developed a core set of genomic tools and a novel collaborative strategy to probe gene expression in diverse songbird species and natural contexts. RESULTS: We end-sequenced cDNAs from zebra finch brain and incorporated additional sequences from community sources into a database of 86,784 high quality reads. These assembled into 31,658 non-redundant contigs and singletons, which we annotated via BLAST search of chicken and human databases. The results are publicly available in the ESTIMA:Songbird database. We produced a spotted cDNA microarray with 20,160 addresses representing 17,214 non-redundant products of an estimated 11,500–15,000 genes, validating it by analysis of immediate-early gene (zenk) gene activation following song exposure and by demonstrating effective cross hybridization to genomic DNAs of other songbird species in the Passerida Parvorder. Our assembly was also used in the design of the "Lund-zfa" Affymetrix array representing ~22,000 non-redundant sequences. When the two arrays were hybridized to cDNAs from the same set of male and female zebra finch brain samples, both arrays detected a common set of regulated transcripts with a Pearson correlation coefficient of 0.895. To stimulate use of these resources by the songbird research community and to maintain consistent technical standards, we devised a "Community Collaboration" mechanism whereby individual birdsong researchers develop experiments and provide tissues, but a single individual in the community is responsible for all RNA extractions, labelling and microarray hybridizations. CONCLUSION: Immediately, these results set the foundation for a coordinated set of 25 planned experiments by 16 research groups probing fundamental links between genome, brain, evolution and behavior in songbirds. Energetic application of genomic resources to research using songbirds should help illuminate how complex neural and behavioral traits emerge and evolve

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution