Triassic collision of western Tianshan orogenic belt, China: Evidence from SHRIMP U-Pb dating of zircon from HP/UHP eclogitic rocks

A newly recognized ultrahigh-pressure (UHP) terrane in the Chinese Western Tianshan orogenic belt contains blueschists, eclogites and metapelites. This belt extends westward to the "South Tianshan" in Tajikistan, Kyrgyzstan, Kazakhstan and Uzbekistan fo

High prevalence of HPV 51 in an unvaccinated population and implications for HPV vaccines

Human papillomavirus (HPV) is detected in 99.7% of cervical cancers. Current vaccines target types 16 and 18. Prior to vaccination implementation, a prospective cohort study was conducted to determine baseline HPV prevalence in unvaccinated women in Wales; after HPV16 and HPV18, HPV 51 was found to be most prevalent. This study aimed to re-assess the unexpected high prevalence of HPV 51 and consider its potential for type-replacement. Two hundred HPV 51 positive samples underwent re-analysis by repeating the original methodology using HPV 51 GP5+/6+ PCR-enzyme immunoassay, and additionally a novel assay of HPV 51 E7 PCR. Data were correlated with age, social deprivation and cytology. Direct repeat of HPV 51 PCR-EIA identified 146/195 (75.0%) samples as HPV 51 positive; E7 PCR identified 166/195 (85.1%) samples as HPV 51 positive. HPV 51 prevalence increased with cytological grade. The prevalence of HPV 51 in the pre-vaccinated population was truly high. E7 DNA assays may offer increased specificity for HPV genotyping. Cross-protection of current vaccines against less-prevalent HPV types warrants further study. This study highlights the need for longitudinal investigation into the prevalence of non-vaccine HPV types, especially those phylogenetically different to vaccine types for potential type-replacement. Ongoing surveillance will inform future vaccines

VLT/XSHOOTER and Subaru/MOIRCS spectroscopy of HUDF.YD3: no evidence for Lyman emission at z = 8.55

We present spectroscopic observations with VLT/XSHOOTER and Subaru/MOIRCS of a relatively bright Y-band drop-out galaxy in the Hubble Ultra Deep Field (HUDF), first selected by Bunker et al., McLure et al. and Bouwens et al. to be a likely z ≈ 8–9 galaxy on the basis of its colours in the Hubble Space Telescope (HST) Advanced Camera for Surveys and Wide Field Camera 3 images. This galaxy, HUDF.YD3 (also known as UDFy-38135539), has been targetted for VLT/SINFONI integral field spectroscopy by Lehnert et al., who published a candidate Lyman α emission line at z = 8.55 from this source. In our independent spectroscopy using two different infrared spectrographs (5 h with VLT/XSHOOTER and 11 h with Subaru/MOIRCS), we are unable to reproduce this line. We do not detect any emission line at the spectral and spatial location reported in Lehnert et al., despite the expected signal in our combined MOIRCS and XSHOOTER data being 5σ. The line emission also seems to be ruled out by the faintness of this object in recently extremely deep F105W (Y band) HST/WFC 3 imaging from HUDF12; the line would fall within this filter and such a galaxy should have been detected at YAB = 28.6 mag (∼20σ) rather than the marginal YAB ≈ 30 mag observed in the Y-band image, >3 times fainter than would be expected if the emission line was real. Hence, it appears highly unlikely that the reported Lyman α line emission at z > 8 is real, meaning that the highest redshift sources for which Lyman α emission has been seen are at z = 6.9-7.2. It is conceivable that Lyman α does not escape galaxies at higher redshifts, where the Gunn–Peterson absorption renders the Universe optically thick to this line. However, deeper spectroscopy on a larger sample of candidate z > 7 galaxies will be needed to test this

Phylodynamic analysis of an emergent Mycobacterium bovis outbreak in an area with no previously known wildlife infections

1. Understanding how an emergent pathogen successfully establishes itself and persists in a previously unaffected population is a crucial problem in disease ecology, with important implications for disease management. In multi-host pathogen systems this problem is particularly difficult, as the importance of each host species to transmission is often poorly characterised, and the disease epidemiology is complex. Opportunities to observe and analyse such emergent scenarios are few. 2. Here, we exploit a unique dataset combining densely-collected data on the epidemiological and evolutionary characteristics of an outbreak of Mycobacterium bovis (the causative agent of bovine tuberculosis, bTB) in a population of cattle and badgers in an area considered low-risk for bTB, with no previous record of either persistent infection in cattle, or of any infection in wildlife. We analyse the outbreak dynamics using a combination of mathematical modelling, Bayesian evolutionary analyses, and machine learning. 3. Comparison to M. bovis whole-genome sequences from Northern Ireland confirmed this to be a single introduction of the pathogen from the latter region, with evolutionary analysis supporting an introduction directly into the local cattle population six years prior to its first discovery in badgers. 4. Once introduced, the evidence supports M. bovis epidemiological dynamics passing through two phases, the first dominated by cattle-to-cattle transmission before becoming established in the local badger population. 5. Synthesis and applications. The raw data object of this analysis were used to support decisions regarding the control of a M. bovis emergent outbreak, of considerable concern because of the geographical distance from previously known high-risk areas. Our further analyses, estimating the time of introduction (and therefore the likely magnitude of any hidden outbreak) and the rates of cross-species transmission, provided valuable confirmation that the extent and focus of the imposed controls were appropriate. Not only these findings strengthen the call for genomic surveillance, but they also pave the path for future outbreaks control, providing insights for more rapid and decisive evidence-based decision-making. As the methods we used and developed are agnostic to the disease itself, they are also valuable for other slowly transmitting pathogens

Non-toxic metal-cyclam complexes, a new class of compounds with potency against drug-resistant Mycobacterium tuberculosis

Tuberculosis (TB) accounted for 1.5 million deaths in 2014 and new classes of anti-TB drugs are required. We re-port a class of functionalized 1,8-disubstituted cyclam derivatives that display low micromolar activity against pathogenic myco-bacteria. These compounds inhibit intracellular growth of Mycobacterium tuberculosis, are non-toxic to human cell lines and are active against multidrug-resistant M. tuberculosis strains, indicating a distinct mode of action. These compounds warrant further appraisal as novel agents to control TB in humans.This work was supported by the National Health and Medical Research Council (NHMRC) Project APP1084266, the NHMRC Center of Research Excellence in Tuberculosis Control (APP1043225) and the University of Sydney Sydnovate Fund. We acknowledge the Centre for Drug Candidate Optimization, Monash University for the ADME studie

Anthropogenic natal environmental effects on life histories in a wild bird population

Recent work suggests that the environment experienced in early life can alter life histories in wild populations [1, 2, 3, 4 and 5], but our understanding of the processes involved remains limited [6 and 7]. Since anthropogenic environmental change is currently having a major impact on wild populations [8], this raises the possibility that life histories may be influenced by human activities that alter environmental conditions in early life. Whether this is the case and the processes involved remain unexplored in wild populations. Using 23 years of longitudinal data on the Mauritius kestrel (Falco punctatus), a tropical forest specialist, we found that females born in territories affected by anthropogenic habitat change shifted investment in reproduction to earlier in life at the expense of late life performance. They also had lower survival rates as young adults. This shift in life history strategy appears to be adaptive, because fitness was comparable to that of other females experiencing less anthropogenic modification in their natal environment. Our results suggest that human activities can leave a legacy on wild birds through natal environmental effects. Whether these legacies have a detrimental effect on populations will depend on life history responses and the extent to which these reduce individual fitness

Almost invisible : a review of inclusion of LGBTQI people with cancer in online patient information resources

Objective: This review assessed the inclusion of lesbian, gay, bisexual, trans, queer and/or intersex (LGBTQI) people in online cancer information. Methods: The websites of Australian cancer organizations were reviewed to identify if they included LGBTQI people and the extent and nature of this inclusion. Websites that did not include LGBTQI people were then reviewed to identify if information was implicitly LGBTQI inclusive. International LGBTQI cancer information resources were reviewed to identify key content. Results: Of sixty-one Australian cancer organization websites reviewed, eight (13%) mentioned LGBTQI people, including 13 information resources targeted to LGBTQI people and 19 general cancer information resources that mentioned LGBTQI people. For Australian cancer websites that did not mention LGBTQI people, 88% used gender neutral language to refer to partners, 69% included a range of sexual behaviours, 13% used gender neutral language when referring to hormones or reproductive anatomy but none acknowledged diverse relationship types. Internationally, 38 LGBTQI-specific cancer information resources were identified. Conclusions: Cancer patient information resources need to be LGBTQI inclusive. LGBTQI-targeted resources are required to address this population's unique needs and improve cultural safety and cancer outcomes. Practice implications: Recommendations are provided for LGBTQI inclusive cancer patient information resources

Curcuphenol possesses an unusual histone deacetylase enhancing activity that counters immune escape in metastatic tumours

Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentation machinery (APM) in invasive cancers, thereby resurrecting the immune recognition of metastatic tumours. Two synthetic curcuphenol analogues, were prepared by informed design that demonstrated consistent induction of APM expression in metastatic prostate and lung carcinoma cells. Both analogues were subsequently found to possess a previously undescribed histone deacetylase (HDAC)-enhancing activity. Remarkably, the H3K27ac ChIPseq analysis of curcuphenol-treated cells reveals that the induced epigenomic marks closely resemble the changes in genome-wide pattern observed with interferon-γ, a cytokine instrumental for orchestrating innate and adaptive immunity. These observations link dietary components to modifying epigenetic programs that modulate gene expression guiding poised immunity

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation