Reducing recurrent care proceedings: initial evidence from new interventions

The English family justice system faces a crisis of recurrence. As many as one in four birth mothers involved in public law care proceedings in English family courts are likely to reappear in a subsequent set of proceedings within seven years. These mothers are involved in up to one-third of total care applications, as they are – by definition – linked to more than one child . Few birth mothers experiencing the removal of a child to care are offered any follow-up support, despite often facing multiple challenges including poverty, addiction, domestic violence and mental health problems. Since 2011, however, a number of new services have been established to begin to address their unmet needs. This article summarises the findings of the first academic-led evaluation of two of these initiatives. Presenting evidence from a mixed-methods evaluative study, it concludes that the new services were able to foster relationships that ‘worked’ in reducing recurrent proceedings. None of the women engaging with the services went on to experience what could be described as a ‘rapid repeat pregnancy’ within the evaluation window. Just as significantly, a number of clients reported some improvement in their psychological functioning, and the practitioners involved reported positively on their experience of delivering and managing innovative services. The article closes with a discussion of the challenges of evaluating personalised, strengths-based interventions and the possibilities of evidencing empowerment in these cases

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Plant-Symbiotic Fungi as Chemical Engineers: Multi-Genome Analysis of the Clavicipitaceae Reveals Dynamics of Alkaloid Loci

The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Changes in appetite, energy intake, body composition and circulating ghrelin constituents during an incremental trekking ascent to high altitude

Purpose Circulating acylated ghrelin concentrations are associated with altitude-induced anorexia in laboratory environments, but have never been measured at terrestrial altitude. This study examined time course changes in appetite, energy intake, body composition, and ghrelin constituents during a high-altitude trek. Methods Twelve participants [age: 28(4) years, BMI 23.0(2.1) kg m−2] completed a 14-day trek in the Himalayas. Energy intake, appetite perceptions, body composition, and circulating acylated, des-acylated, and total ghrelin concentrations were assessed at baseline (113 m, 12 days prior to departure) and at three fixed research camps during the trek (3619 m, day 7; 4600 m, day 10; 5140 m, day 12). Results Relative to baseline, energy intake was lower at 3619 m (P = 0.038) and 5140 m (P = 0.016) and tended to be lower at 4600 m (P = 0.056). Appetite perceptions were lower at 5140 m (P = 0.027) compared with baseline. Acylated ghrelin concentrations were lower at 3619 m (P = 0.046) and 4600 m (P = 0.038), and tended to be lower at 5140 m (P = 0.070), compared with baseline. Des-acylated ghrelin concentrations did not significantly change during the trek (P = 0.177). Total ghrelin concentrations decreased from baseline to 4600 m (P = 0.045). Skinfold thickness was lower at all points during the trek compared with baseline (P ≤ 0.001) and calf girth decreased incrementally during the trek (P = 0.010). Conclusions Changes in plasma acylated and total ghrelin concentrations may contribute to the suppression of appetite and energy intake at altitude, but differences in the time course of these responses suggest that additional factors are also involved. Interventions are required to maintain appetite and energy balance during trekking at terrestrial altitudes

Crop Updates 2002 - Geraldton

This session covers twenty seven papers from different authors: 1. Taking the Why out of Wyalkatchem – the new widely adapted wheat variety, Steve Penny Jr, Department of Agriculture 2. Future wheat varieties, Robin Wilson, Iain Barclay,Robyn McLean, Robert Loughman, Jenny Garlinge, Bill Lambe, Neil Venn and Peter Clarke Department of Agriculture 3. Maximising wheat variety performance through agronomic management, Wal Anderson, Raffaele Del Cima, James Bee, Darshan Sharma, Sheena Lyon, Melaine Kupsch, Mohammad Amjad, Pam Burgess, Veronika Reck, Brenda Shackley, Ray Tugwell, Bindi Webb and Steve Penny Jr Department of Agriculture 4. Cereal rust update 2002 – a new stem rust on Camm wheat, Robert Loughman1and Robert Park2 1Department of Agriculture, 2University of Sydney 5. Influence of nutrition and environmental factors on seed vigour in wheat, Darshan Sharma, Wal Anderson and Daya Patabendige, Department of Agriculture 6. Cereal aphids and direct feeding damage to cereals, Phil Michael, Department of Agriculture 7. A decision support system for control of aphids and BYDV in cereal crops, Debbie Thackray, Jenny Hawkes and Roger Jones, Department of Agriculture and Centre for Legumes in Mediterranean Agriculture 8. Summary of 2001 weather and seasonal prospects for 2002, David Stephens, Department of Agriculture 9. Towards a management package for grain protein in lupins, Bob French, Senior Research Officer, Department of Agriculture 10. Lupin genotypes respond differently to potash, Bob French and Laurie Wahlsten, Senior Research Officer and Technical Officer, Department of Agriculture 11. Time of harvest for improved seed yield of pulses, G. Riethmuller and B. French, Department of Agriculture 12. Comparing the phosphorus requirement of field pea and wheat, M. Bolland and P. White, Department of Agriculture Western Australia 13. Field pea variety evaluation, T. Khan, Department of Agriculture Western Australia 14. Diamondback moth (DBM) in canola, Kevin Walden, Department of Agriculture 15. WA blackleg resistance ratings on canola varieties for 2002, Ravjit Khangura, Martin J. Barbetti and Graham Walton, Department of Agriculture 16. The effect of single or multiple spray treatments on the control of Diamondback moth (Plutella xylostella) and yield of canola at Wongan Hills, Françoise Berlandier, Paul Carmody and Christiaan Valentine, Department of Agriculture 17. Perennial pastures in annual cropping systems: Lucerne and beyond, Roy Latta and Keith Devenish, Department of Agriculture 18. Nutrition in 2002: Decisions to be made as a result of last season, Bill Bowden,Department of Agriculture 19. Profitability of deep banding lime, Michael O\u27Connell, Chris Gazey and David Gartner, Department of Agriculture 20. Economic comparisons of farming systems for the medium rainfall northern sandplain, Caroline Peek and David Rogers, Department of Agriculture 21. The use of Twist Fungus as a biosecurity measure against Annual Ryegrass Toxicity (ARGT), Greg Shea, GrainGuard Coordinator and George Yan, Biological and Resource Technology 22. Major outcomes from IWM demonstration sites, Alexandra Douglas, Department of Agriculture 23. Understanding the weed seed bank life of important agricultural weeds, Sally Peltzer and Paul Matson, Department of Agriculture 24. Seeding rate, row spacing and herbicides for weed control, David Minkey, Department of Agriculture 25. Improving weed control in grazed pastures using legumes with low palatability, Clinton Revell and Giles Glasson, Department of Agriculture, Dean Thomas, Faculty of Agriculture, University of Western Australia 26. Group F resistant wild radish: What’s new? Aik Cheam1, Siew Lee1and Mike Clarke2, 1Department of Agriculture WA, 2Aventis Crop Science 27. Knockdown herbicides do not reliably kill small grass weeds, Peter Newman and Glenn Adam, Department of Agricultur