rfTSP: A Non-parametric predictive model with order-based feature selection for transcriptomic data

Genomic data has strong potential to predict biologic classifications using gene expression data. For example, tumor subtype can be determined using machine learning models and gene expression profiles. We propose the use of Top Scoring Pairs in combination with machine learning to improve inter-study prediction of genomic profiles. Inter-study prediction refers to two studies that are completely independent either in terms of platform or tissue. Top Scoring Pairs (TSPs) rank pairs of genes according to how well they are expressed between different groups of subjects. For example, gene A will be lowly expressed in cases, and gene B will be highly expressed in controls, while gene A will be highly expressed in controls, and gene B will be lowly expressed in cases. The pairs demonstrate an inverse relationship with respect to one and another. Using TSPs act not only as a feature selection step, but also allows for a non parametric method that transforms the continuous expression data to 0,1, which is based on the rank of the pairs. Due to the robust nature of the transformed data, our methods demonstrate that the use of TSP binary data is much more effective in prediction than continuous data, particularly in cross study prediction. Furthermore, we extend the use of TSPs to not only binary and multi-class label prediction, but also continuous classification. The objective of this paper is to demonstrate how using dichotomized data from TSPs as the feature space for machine learning methods, particularly random forest, returns stronger prediction accuracy across independent studies than traditional machine learning techniques with log2 and quantile normalization of data. This work has significant public health impact as accurate genomic prediction is crucial for early detection of many serious illnesses such as cancer

Contemporary management of drug-packers

Experience with management of drug-packers (mules) is variable among different centres. However, despite a recorded increase in drug trafficking in general, as yet, no unified, clear guidelines exist to guide the medical management of those who only occasionally encounter these individuals. We describe our recent experience with this growing problem and discuss the most salient points concerning the contemporary management of body packers. Our recent experience demonstrates that type IV packages may now be managed conservatively for the most part

On Pediatric Vaccines and Catholic Social Teaching

Determining whether, and when, to get one\u27s children vaccinated has become an increasingly controversial decision, often leaving parents fearful of making the “wrong” choice. Part of the challenge stems from the fact that what is rationally optimal for an individual is inherently at odds with the best outcome for the community, meaning that if everyone acted out of self-interest with respect to pediatric vaccines, communal health would suffer significantly. Given these tensions, the issue of pediatric vaccines benefits greatly from the nuanced assessment of Catholic social teaching. Specifically, the Pontifical Council for Justice and Peace\u27s “four permanent principles” of human dignity, the common good, subsidiarity, and solidarity highlight the issues involved and help parents navigate this significant medical choice with a more informed conscience and a greater sense of their moral responsibilities. The end result is a fruitful alignment between Catholic social teaching and ethics in ordinary life

The Effect of Various Pasture-based Systems of Milk Production on Animal Performance in the Northeast Region of Ireland

End of Project ReportThe potential of Irish soils to grow grass throughout the year and success in utilizing grass are key factors affecting output and profitability of dairy production systems (Shalloo et al., 2004). In the Northeast region of Ireland, the potential grazing season is shortened due to impeded land drainage, topography, high rainfall and northerly aspect. The main focus of the Ballyhaise research programme is to develop more sustainable production systems suitable to the limitations of the region with a specific focus on grass growth and utilization. Progress in these technologies will improve the competitiveness of dairying in the Northeast region. We are also now faced with a new economic environment with market forecasts predicting a steady decline in dairy product prices for Irish dairy farmers while input prices continue to increase. It has been shown from previous studies that dairy farmers need to expand and/or increase the efficiency of their dairy operation to maintain their real farm incomes over the coming years (Breen and Hennessey, 2003). It is likely that land purchase price will continue to be high in future years. Firstly, dairy farmers can continue at their current level of production and efficiency, and suffer a decline in farm profit as milk price falls. It is likely that greater amounts of milk quota will become available in the coming years; therefore many dairy farmers will have the option to increase production. Expansion opportunities will be limited by the key constraints such as labour supply and cost, capital cost, milk quota availability and price and availability of land around the milking parlour. Labour efficient work practices will have to be adopted on farms to allow one operator to manage a greater number of cows. The objective of this experiment was to examine the effect of two divergent pasture-based systems of milk production on animal performance over a two-year period and to subsequently describe the optimum system for dairy farmers in the Northeast region both now and into the future

Rape and respectability: ideas about sexual violence and social class

Women on low incomes are disproportionately represented among sexual violence survivors, yet feminist research on this topic has paid very little attention to social class. This article blends recent research on class, gender and sexuality with what we know about sexual violence. It is argued that there is a need to engage with classed distinctions between women in terms of contexts for and experiences of sexual violence, and to look at interactions between pejorative constructions of working-class sexualities and how complainants and defendants are perceived and treated. The classed division between the sexual and the feminine, drawn via the notion of respectability, is applied to these issues. This piece is intended to catalyse further research and debate, and raises a number of questions for future work on sexual violence and social class

The impact of routine open nonsuction drainage on fluid accumulation after thyroid surgery: a prospective randomised clinical trial.

Background: Thyroid drains following thyroid surgery are routinely used despite minimal supportive evidence. Our aim in this study is to determine the impact of routine open drainage of the thyroid bed postoperatively on ultrasound-determined fluid accumulation at 24 hours. Methods: We conducted a prospective randomised clinical trial on patients undergoing thyroid surgery. Patients were randomly assigned to a drain group (n = 49) or a no-drain group (n = 44) immediately prior to wound closure. Patients underwent a neck ultrasound on day 1 and day 2 postoperatively. After surgery, we evaluated visual analogue scale pain scores, postoperative analgesic requirements, self-reported scar satisfaction at 6 weeks and complications. Results: There was significantly less mean fluid accumulated in the drain group on both day 1, 16.4 versus 25.1 ml (P-value = 0.005), and day 2, 18.4 versus 25.7 ml (P-value = 0.026), following surgery. We found no significant differences between the groups with regard to length of stay, scar satisfaction, visual analogue scale pain score and analgesic requirements. There were four versus one wound infections in the drain versus no-drain groups. This finding was not statistically significant (P = 0.154). No life-threatening bleeds occurred in either group. Conclusions: Fluid accumulation after thyroid surgery was significantly lessened by drainage. However, this study did not show any clinical benefit associated with this finding in the non-emergent setting. Drains themselves showed a trend indicating that they may augment infection rates. The results of this study suggest that the frequency of acute life-threatening bleeds remains extremely low following abandoning drains. We advocate abandoning routine use of thyroid drains. Trial registration: ISRCTN94715414

Red Sea SAR11 and Prochlorococcus Single-cell Genomes Reflect Globally Distributed Pangenomes

Evidence suggests many marine bacteria are cosmopolitan, with widespread but sparse strains poised to seed abundant populations under conducive growth conditions. However, studies supporting this "microbial seed bank" hypothesis have analyzed taxonomic marker genes rather than whole genomes/metagenomes, leaving open the possibility that disparate ocean regions harbor endemic gene content. The Red Sea is isolated geographically from the rest of the ocean and has a combination of high irradiance, high temperature, and high salinity that is unique among the oceans; we therefore asked whether it harbors endemic gene content. We sequenced and assembled single-cell genomes of 21 SAR11 (subclades Ia, Ib, Id, and II) and 5 Prochlorococcus (ecotype HLII) samples from the Red Sea and combined them with globally sourced reference genomes to cluster genes into ortholog groups (OGs). Ordination of OG composition could distinguish clades, including phylogenetically cryptic Prochlorococcus ecotypes LLII and LLIII. Compared with reference genomes, 1% of Prochlorococcus and 17% of SAR11 OGs were unique to the Red Sea genomes (RS-OGs). Most (83%) RS-OGs had no annotated function, but 65% of RS-OGs were expressed in diel Red Sea metatranscriptomes, suggesting they are functional. Searching Tara Oceans metagenomes, RS-OGs were as likely to be found as non-RS-OGs; nevertheless, Red Sea and other warm samples could be distinguished from cooler samples using the relative abundances of OGs. The results suggest that the prevalence of OGs in these surface ocean bacteria is largely cosmopolitan, with differences in population metagenomes manifested by differences in relative abundance rather than complete presence/absence of OGs.IMPORTANCE Studies have shown that as we sequence seawater from a selected environment deeper and deeper, we approach finding every bacterial taxon known for the ocean as a whole. However, such studies have focused on taxonomic marker genes rather than on whole genomes, raising the possibility that the lack of endemism results from the method of investigation. We took a geographically isolated water body, the Red Sea, and sequenced single cells from it. We compared those single-cell genomes to available genomes from around the ocean and to ocean-spanning metagenomes. We showed that gene ortholog groups found in Red Sea genomes but not in other genomes are nevertheless common across global ocean metagenomes. These results suggest that Baas Becking's hypothesis "everything is everywhere, but the environment selects" also applies to gene ortholog groups. This widely dispersed functional diversity may give oceanic microbial communities the functional capacity to respond rapidly to changing conditions

Identification of Acinetobacter baumannii loci for capsular polysaccharide (KL) and lipooligosaccharide outer core (OCL) synthesis in genome assemblies using curated reference databases compatible with Kaptive.

Multiply antibiotic-resistant Acinetobacter baumannii infections are a global public health concern and accurate tracking of the spread of specific lineages is needed. Variation in the composition and structure of capsular polysaccharide (CPS), a critical determinant of virulence and phage susceptibility, makes it an attractive epidemiological marker. The outer core (OC) of lipooligosaccharide also exhibits variation. To take better advantage of the untapped information available in whole genome sequences, we have created a curated reference database of 92 publicly available gene clusters at the locus encoding proteins responsible for biosynthesis and export of CPS (K locus), and a second database for 12 gene clusters at the locus for outer core biosynthesis (OC locus). Each entry has been assigned a unique KL or OCL number, and is fully annotated using a simple, transparent and standardized nomenclature. These databases are compatible with Kaptive, a tool for in silico typing of bacterial surface polysaccharide loci, and their utility was validated using (a) >630 assembled A. baumannii draft genomes for which the KL and OCL regions had been previously typed manually, and (b) 3386 A. baumannii genome assemblies downloaded from NCBI. Among the previously typed genomes, Kaptive was able to confidently assign KL and OCL types with 100?% accuracy. Among the genomes retrieved from NCBI, Kaptive detected known KL and OCL in 87 and 90?% of genomes, respectively, indicating that the majority of common KL and OCL types are captured within the databases; 13 of the 92 KL in the database were not detected in any publicly available whole genome assembly. The failure to assign a KL or OCL type may indicate incomplete or poor-quality genomes. However, further novel variants may remain to be documented. Combining outputs with multilocus sequence typing (Institut Pasteur scheme) revealed multiple KL and OCL types in collections of a single sequence type (ST) representing each of the two predominant globally distributed clones, ST1 of GC1 and ST2 of GC2, and in collections of other clones comprising >20 isolates each (ST10, ST25, and ST140), indicating extensive within-clone replacement of these loci. The databases are available at https://github.com/katholt/Kaptive and will be updated as further locus types become available

Distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model of CHARGE syndrome

Mutations in the gene encoding the ATP dependent chromatin‐remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital‐urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio‐temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay