Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.

We investigated whether older adults are more likely than younger adults to violate a foundational property of rational decision making, the axiom of transitive preference. Our experiment consisted of two groups, older (ages 60-75; 21 participants) and younger (ages 18-30; 20 participants) adults. We used Bayesian model selection to investigate whether individuals were better described via (transitive) weak order-based decision strategies or (possibly intransitive) lexicographic semiorder decision strategies. We found weak evidence for the hypothesis that older adults violate transitivity at a higher rate than younger adults. At the same time, a hierarchical Bayesian analysis suggests that, in this study, the distribution of decision strategies across individuals is similar for both older and younger adults.

A new transmission electron microscopy (TEM) specimen preparation method that utilizes a combination of focused ion beam (FIB) methods and ultramicrotomy is demonstrated. This combined method retains the benefit of site-specific sampling by FIB but eliminates ion beam-induced damage except at specimen edges and allows recovery of many consecutive sections. It is best applied to porous and/or fine-grained materials that are amenable to ultramicrotomy but are located in bulk samples that are not. The method is ideal for unique samples from which every specimen is precious, and we demonstrate its utility on fine-grained material from the one-of-a-kind Paris meteorite. Compared with a specimen prepared by conventional FIB methods, the final sections are uniformly thin and free from re-deposition and curtaining artifacts common in FIB specimens prepared from porous, heterogeneous samples.

Salmonella enterica serovar Wangata (S. Wangata) is an important cause of endemic salmonellosis in Australia, with human infections occurring from undefined sources. This investigation sought to examine possible environmental and zoonotic sources for human infections with S. Wangata in north-eastern New South Wales (NSW), Australia. The investigation adopted a One Health approach and was comprised of three complimentary components: a case–control study examining human risk factors; environmental and animal sampling; and genomic analysis of human, animal and environmental isolates. Forty-eight human S. Wangata cases were interviewed during a 6-month period from November 2016 to April 2017, together with 55 Salmonella Typhimurium (S. Typhimurium) controls and 130 neighbourhood controls. Indirect contact with bats/flying foxes (S. Typhimurium controls (adjusted odds ratio (aOR) 2.63, 95% confidence interval (CI) 1.06–6.48)) (neighbourhood controls (aOR 8.33, 95% CI 2.58–26.83)), wild frogs (aOR 3.65, 95% CI 1.32–10.07) and wild birds (aOR 6.93, 95% CI 2.29–21.00) were statistically associated with illness in multivariable analyses. S. Wangata was detected in dog faeces, wildlife scats and a compost specimen collected from the outdoor environments of cases’ residences. In addition, S. Wangata was detected in the faeces of wild birds and sea turtles in the investigation area. Genomic analysis revealed that S. Wangata isolates were relatively clonal. Our findings suggest that S. Wangata is present in the environment and may have a reservoir in wildlife populations in north-eastern NSW. Further investigation is required to better understand the occurrence of Salmonella in wildlife groups and to identify possible transmission pathways for human infections.

During May 2015, an increase in Salmonella Agona cases was reported from western Sydney, Australia. We examine the public health actions used to investigate and control this increase. A descriptive case-series investigation was conducted. Six outbreak cases were identified; all had consumed cooked tuna sushi rolls purchased within a western Sydney shopping complex. Onset of illness for outbreak cases occurred between 7 April and 24 May 2015. Salmonella was isolated from food samples collected from the implicated premise and a prohibition order issued. No further cases were identified following this action. Whole genome sequence (WGS) analysis was performed on isolates recovered during this investigation, with additional S. Agona isolates from sporadic-clinical cases and routine food sampling in New South Wales, January to July 2015. Clinical isolates of outbreak cases were indistinguishable from food isolates collected from the implicated sushi outlet. Five additional clinical isolates not originally considered to be linked to the outbreak were genomically similar to outbreak isolates, indicating the point-source contamination may have started before routine surveillance identified an increase. This investigation demonstrated the value of genomics-guided public health action, where near real-time WGS enhanced the resolution of the epidemiological investigation.

Although the title of this paper, for brevity, refers to engine performance monitoring, in fact we mean performance and condition monitoring. In presenting such a paper with particular emphasis on the problems that arise for the Operator with relatively small aircraft fleets operating in the main over short stages, although the comments we have to make are based on TAA experience, a similar situation must exist for any operator with a multiplicity of aircraft types and relatively small numbers of each.

We refer to performance and condition monitoring to define the complete task, as it is essential to correlate performance parameters to condition evidence such as vibration level or lubricant deterioration status to obtain a useful perspective.

Monitoring infections and risk in people who inject drugs (PWID) is important for informing public health responses. In 2011, a novel hepatitis C antibody (anti-HCV) avidity-testing algorithm to identify samples compatible with recent primary infection was introduced into a national surveillance survey. PWID are recruited annually, through >60 needle-and-syringe programmes and prescribing services. Of the 980 individuals that could have been at risk of HCV infection, there were 20 (2%) samples that were compatible with recent primary infection. These were more common among: those imprisoned ⩾5 times [8/213; adjusted odds ratio (aOR) 8·7, 95% confidence interval (CI) 2·04–37·03]; women (8/230; aOR 3·8, 95% CI 1·41–10·38); and those ever-infected with hepatitis B (5/56; aOR 6·25, 95% CI 2·12–18·43). This study is the first to apply this algorithm and to examine the risk factors associated with recently acquired HCV infection in a national sample of PWID in the UK. These findings highlight underlying risks and suggest targeted interventions are needed.

Sandy (sdy) is a mouse mutant with diluted pigmentation which recently arose in the DBA/2J strain. Genetic tests indicate it is caused by an autosomal recessive mutation on mouse Chromosome 13 near the cr and Xt genetic loci. This mutation is different genetically and hematologically from previously described mouse pigment mutations with storage pool deficiency (SPD). The sandy mutant has diluted pigmentation in both eyes and fur, is fully viable and has prolonged bleeding times. Platelet serotonin levels are extremely low although ATP dependent acidification activity of platelet organelles appears normal. Also, platelet dense granules are extremely reduced in number when analysed by electron microscopy of unfixed platelets. Platelets have abnormal uptake and flashing of the fluorescent dye mepacrine. Secretion of lysosomal enzymes from kidney and from thrombin-stimulated platelets is depressed 2- and 3-fold, and ceroid pigment is present in kidney. Sandy platelets have a reduced rate of aggregation induced by collagen. The sandy mutant has an unusually severe dense granule defect and thus may be an appropriate model for cases of human Hermansky-Pudlak syndrome with similarly extreme types of SPD. It represents the tenth example of a mouse mutant with simultaneous defects in melanosomes, lysosomes and/or platelet dense granules.

High-pressure studies have been performed on heavy rare earth metals Terbium (Tb) to 155 GPa and Holmium (Ho) to 134 GPa in a diamond anvil cell at room temperature. The following crystal structure sequence was observed in both metals hcp ⟶ Sm-type ⟶ dhcp ⟶ distorted fcc (hR-24) ⟶ monoclinic (C2/m) with increasing pressure. The last transformation to a low symmetry monoclinic phase is accompanied by a volume collapse of 5 % for Tb at 51 GPa and a volume collapse of 3 % for Ho at 103 GPa. This volume collapse under high pressure is reminiscent of f-shell delocalization in light rare earth metal Cerium (Ce), Praseodymium (Pr), and heavy actinide metals Americium (Am) and Curium (Cm). The orthorhombic Pnma phase that has been reported in Am and Cm after f-shell delocalization is not observed in heavy rare earth metals under high pressures.

Photodynamic therapy (PDT) offers potential as a non-invasive treatment of periodontal disease. In this study, microcosm biofilms were grown in vitro under conditions designed to mimic subgingival plaques typically found in patients with periodontitis. To investigate potential PDT modalities, biofilms were exposed to light from a helium/neon laser in conjunction with a photosensitizer, toluidine blue O (TBO), at varying output and concentration, respectively. To determine cytotoxic effects, viability profiling was undertaken on whole biofilms using standard plating methods, and on horizontal cross-sections of biofilms using confocal laser-scanning microscopy (CLSM) in conjunction with a differential viability stain. A light energy dose of 94.5 J in combination with 81.7 μM TBO was found to be optimal, achieving significant kills of over 97%. CLSM enabled visualization of the effects of PDT in three dimensions. Viability profiling of the CLSM images revealed that lethal photosensitization was most effective in the upper layers of biofilm. PDT was found to reduce the viability of subgingivally modelled plaques in vitro by a magnitude similar to that of chlorhexidine digluconate, which is commonly used to treat periodontal disease. The findings of this study indicate that PDT may be an effective alternative to conventional modalities in the treatment of periodontal disease.

Nematode assemblages were studied from four sublittoral sites at 50–56 m depth in the Gulf of Maine, north-eastern coast of the USA, within the context of an open ocean aquaculture experimental site. All four sites, two potential impact and two control sites, had a similar muddy–sand bottom and low organic content. Seventy genera in 27 families were recorded from a total of 1072 individuals. All but one taxa could be related to known genera. Family Comesomatidae was the most dominant with close to a third (27·6%) of the total individuals. At the genus level Sabatieria and Setosabatieria were most dominant with a quarter of the total number of individuals. Composition of dominant families from the Gulf of Maine differed from all hitherto reported sublittoral or deep-sea communities from both sides of the Atlantic, and most similar with European estuaries.

Nematode diversity at the genus-level was reasonably high and was comparable with Mediterranean samples. Most diversity indices ordered the four sites similarly with Site 2 as the most diverse followed by Site 5 and then Site 6. By contrast the relative diversity of Site 4 depended on the index employed and its k-dominance curve crossed that of the others. Furthermore based on clustering the community at Site 4 was least similar to the others. Although these observations could be related to the fact that Site 4 is within the expected impact zone of the fish cage, the low number of fish introduced by the time of sampling and the lack of any difference in the maturity index among all the sites argue that these results can be considered before-impact data for further monitoring of the open ocean aquaculture experiment.

A new paradigm where morphological information is documented and communicated using digital multifocal images is introduced. Each video image is comparable with visualization of a specimen under a microscope where the movie can be played back and forth to mimic focusing through a specimen. Web-based and openly accessible digital multifocal images were used to document and effectively communicate the morphology of all the identified genera in this study. This approach for documenting and communicating survey results is proposed as a benchmark for future similar studies that would enhance standardization and quality control of meiofaunal taxonomy, ecology and biodiversity studies.

New high-pressure x-ray diffraction data on uranium metal (99.9 %) in a diamond anvil cell is presented to 100 GPa (Volume compression V/Vo = 0.700) at room temperature using a variety of pressure markers like ruby, copper, and platinum. The diffraction patterns are carefully indexed allowing for reversal of peak positions based on anisotropic compression. We report anisotropic compression of the orthorhombic unit cell with the axial ratio b/a increasing initially to 40 GPa followed by a rapid decrease at higher pressure. On the other hand, axial ratio c/a shows a rapid increase with increasing pressure followed by saturation at megabar pressures. The most recent full potential electronic structure calculations reproduce the increasing tend of axial ratio c/a to 100 GPa but do not explain the variation in the b/a ratio. Our detailed analysis of all available experimental data also indicates that the observed anisotropic effects are intrinsic to Uranium and are independent of the pressure medium used in the high-pressure experiments.

Data on injecting anabolic steroid users, within the national Unlinked Anonymous HIV Prevalence Monitoring Survey of injecting drug users (IDUs) were analysed to determine their risk of acquiring blood borne viruses. One hundred and forty-nine participants who had injected anabolic steroids in the previous month were identified from 1991–6, contributing 1·4% of all participation episodes in the survey. Rates of needle and syringe sharing by steroid users were low. Three of the 149 (2·0%) had anti-HBc and none had anti-HIV in their salivary specimens. The prevalence of anti-HBc in steroid injectors was significantly lower than in heroin injectors, 275/1509 (18%) (P<0·001), or in amphetamine injectors, 28/239 (12%) (P<0·001). The risk of blood borne virus transmission amongst these steroid injectors is low, probably due to hygienic use of injecting equipment and low levels of sharing. It is important to distinguish steroid injectors from other IDUs because they are a distinct group in terms of lifestyle and injecting practice.