Effects of Autism Spectrum Disorder Insurance Mandates on the Treated Prevalence of Autism Spectrum Disorder

Key Findings: State mandates requiring commercial health plans to cover services for children with autism spectrum disorder increased the number of children diagnosed with the disorder. However, diagnosis rates remain much lower than community estimates, suggesting that many commercially insured children with ASD remain undiagnosed or are insured through public plans

Sheep Updates 2015 - Merredin

This session covers fourteen papers from different authors: 1. The Sheep Industry Business Innovation project, Bruce Mullan, Sheep Industry Development Director, Department of Agriculture and Food, Western Australia 2. Western Australian sheep stocktake, Kate Pritchett and Kimbal Curtis, Research Officers, Department of Agriculture and Food, Western Australia 3. Wool demand and supply - short term volatility, long term opportunities, Chris Wilcox, Principal of Poimena Analysis 4. Myths, Facts and the role of animal welfare in farming, Lynne Bradshaw, president, RSPCA WA 5. Latest research and development on breech strike prevention, Geoff Lindon, Manager Productivity and Animal Welfare, AWI 6. Lamb Survival Initiative and 100% Club, Katherine Davies, Development Officer, Department of Agriculture and Food, Western Australia 7. How to boost your lamb survival, Joe Young, Sheep Consultant, R.B. Young and Son 8. Using genomic technology to increase genetic gain, Stephen Lee, School of Animal and Veterinary Sciences, University of Adelaide and Sheep Cooperative Research Centre (CRC) 9. A case study of sheep breeding using the latest genetic and genomic technology, Dawson Bradford Producer, Hillcroft Farms, Narrogin WA 10. The impact of lamb growth on meat quality, Khama Kelman Department of Agriculture and Food, Western Australia 11. Economics of feed lotting - to feed-lot or not?, Lucy Anderton, Economist, Department of Agriculture and Food, Western Australia 12. National Livestock Identification System (NLIS) for sheep and goats - what is the NLIS database? Jaq Pearson Biosecurity Officer, Department of Agriculture and Food, Western Australia 13. Sheep industry traineeships - encouraging a new generation of farmers, Jackie Jarvis, Consultant, Agrifood Labour & Skills 14. Opportunities and challenges facing youth in the sheep and wool industry, Ben Patrick, Yarrawonga Stu

Prion protein interacts with bace1 and differentially regulates its activity towards wild type and swedish mutant amyloid precursor protein

In Alzheimer disease amyloid-β (Aβ) peptides derived from the amyloid precursor protein (APP) accumulate in the brain. Cleavage of APP by the β-secretase BACE1 is the rate-limiting step in the production of Aβ. We have reported previously that the cellular prion protein (PrP(C)) inhibited the action of BACE1 toward human wild type APP (APP(WT)) in cellular models and that the levels of endogenous murine Aβ were significantly increased in PrP(C)-null mouse brain. Here we investigated the molecular and cellular mechanisms underlying this observation. PrP(C) interacted directly with the prodomain of the immature Golgi-localized form of BACE1. This interaction decreased BACE1 at the cell surface and in endosomes where it preferentially cleaves APP(WT) but increased it in the Golgi where it preferentially cleaves APP with the Swedish mutation (APP(Swe)). In transgenic mice expressing human APP with the Swedish and Indiana familial mutations (APP(Swe,Ind)), PrP(C) deletion had no influence on APP proteolytic processing, Aβ plaque deposition, or levels of soluble Aβ or Aβ oligomers. In cells, although PrP(C) inhibited the action of BACE1 on APP(WT), it did not inhibit BACE1 activity toward APP(Swe). The differential subcellular location of the BACE1 cleavage of APP(Swe) relative to APP(WT) provides an explanation for the failure of PrP(C) deletion to affect Aβ accumulation in APP(Swe,Ind) mice. Thus, although PrP(C) exerts no control on cleavage of APP(Swe) by BACE1, it has a profound influence on the cleavage of APP(WT), suggesting that PrP(C) may be a key protective player against sporadic Alzheimer disease

Sheep Updates 2015 - Ravensthorpe

This session covers fourteen papers from different authors: 1. The Sheep Industry Business Innovation project, Bruce Mullan, Sheep Industry Development Director, Department of Agriculture and Food, Western Australia 2. Western Australian sheep stocktake, Kate Pritchett and Kimbal Curtis, Research Officers, Department of Agriculture and Food, Western Australia 3. Wool demand and supply - short term volatility, long term opportunities, Chris Wilcox, Principal of Poimena Analysis 4. Lifetime management for maternal ewes, Mike Hyder, Research Officer, Department of Agriculture and Food, Western Australia 5. National Livestock Identification System (NLIS) for sheep and goats - what is the NLIS database? Leigh Sonnermann, Biosecurity Officer, Department of Agriculture and Food, Western Australia 6. Myths, Facts and the role of animal welfare in farming, Lynne Bradshaw, president, RSPCA WA 7. Latest research and development on breech strike prevention, Geoff Lindon, Manager Productivity and Animal Welfare, AWI 8. Lamb Survival Initiative and 100% Club, Katherine Davies, Development Officer, Department of Agriculture and Food, Western Australia 9. How to boost your lamb survival, Joe Young, Sheep Consultant, R.B. Young and Son 10. Using genomic technology to increase genetic gain, Stephen Lee, School of Animal and Veterinary Sciences, University of Adelaide and Sheep Cooperative Research Centre (CRC) & Ian Robertson, Merinotech WA 11. Economics of feed lotting - to feed-lot or not?, Lucy Anderton, Economist, Department of Agriculture and Food, Western Australia 12. Anameka and other shrubs to fill feed gaps, Hayley Norman CSIRO & Ed Barrett-Lennard UWA & Department of Agriculture and Food, Western Australia 13. Sheep industry traineeships - encouraging a new generation of farmers, Jackie Jarvis, Consultant, Agrifood Labour & Skills 14. Opportunities and challenges facing youth in the sheep and wool industry, Ben Patrick, Yarrawonga Stu

Sheep Updates 2015 - Katanning

This session covers fourteen papers from different authors: 1. The Sheep Industry Business Innovation project, Bruce Mullan, Sheep Industry Development Director, Department of Agriculture and Food, Western Australia 2. Western Australian sheep stocktake, Kate Pritchett and Kimbal Curtis, Research Officers, Department of Agriculture and Food, Western Australia 3. Wool demand and supply - short term volatility, long term opportunities, Chris Wilcox, Principal of Poimena Analysis 4. Lifetime management for maternal ewes, Mike Hyder, Research Officer, Department of Agriculture and Food, Western Australia 5. National Livestock Identification System (NLIS) for sheep and goats - what is the NLIS database? Leigh Sonnermann, Biosecurity Officer, Department of Agriculture and Food, Western Australia 6. Myths, Facts and the role of animal welfare in farming, Lynne Bradshaw, president, RSPCA WA 7. Latest research and development on breech strike prevention, Geoff Lindon, Manager Productivity and Animal Welfare, AWI 8. Lamb Survival Initiative and 100% Club, Katherine Davies, Development Officer, Department of Agriculture and Food, Western Australia 9. How to boost your lamb survival, Joe Young, Sheep Consultant, R.B. Young and Son 10. Using genomic technology to increase genetic gain, Stephen Lee, School of Animal and Veterinary Sciences, University of Adelaide and Sheep Cooperative Research Centre (CRC) & Ian Robertson, Merinotech WA 11. Economics of feed lotting - to feed-lot or not?, Lucy Anderton, Economist, Department of Agriculture and Food, Western Australia 12. Anameka and other shrubs to fill feed gaps, Hayley Norman CSIRO & Ed Barrett-Lennard UWA & Department of Agriculture and Food, Western Australia 13. Sheep industry traineeships - encouraging a new generation of farmers, Jackie Jarvis, Consultant, Agrifood Labour & Skills 14. Opportunities and challenges facing youth in the sheep and wool industry, Ben Patrick, Yarrawonga Stu

SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis

Fibrosis and organ failure is a common endpoint for many chronic liver diseases. Much is known about the upstream inflammatory mechanisms provoking fibrosis and downstream potential for tissue remodeling. However, less is known about the transcriptional regulation in vivo governing fibrotic matrix deposition by liver myofibroblasts. This gap in understanding has hampered molecular predictions of disease severity and clinical progression and restricted targets for antifibrotic drug development. In this study we show the prevalence of SOX9 in biopsies from patients with chronic liver disease correlated with fibrosis severity and accurately predicted disease progression towards cirrhosis. Inactivation of Sox9 in mice protected against both parenchymal and biliary fibrosis, improved liver function and ameliorated chronic inflammation. SOX9 was downstream of mechanosignaling factor, YAP1. These data demonstrate a role for SOX9 in liver fibrosis and open the way for the transcription factor and its dependent pathways as new diagnostic, prognostic and therapeutic targets in patients with liver fibrosis

PAK1-dependent mechanotransduction enables myofibroblast nuclear adaptation and chromatin organization during fibrosis.

Myofibroblasts are responsible for scarring during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state and increasing profibrotic phenotype. Here, we show mechanical stress from progressive scarring induces nuclear softening and de-repression of heterochromatin. The parallel loss of H3K9Me3 enables a permissive state for distinct chromatin accessibility and profibrotic gene regulation. Integrating chromatin accessibility profiles with RNA expression provides insight into the transcription network underlying the switch in profibrotic myofibroblast states, emphasizing mechanoadaptive regulation of PAK1 as key drivers. Through genetic manipulation in liver and lung fibrosis, loss of PAK1-dependent signaling impairs the mechanoadaptive response in vitro and dramatically improves fibrosis in vivo. Moreover, we provide human validation for mechanisms underpinning PAK1-mediated mechanotransduction in liver and lung fibrosis. Collectively, these observations provide insight into the nuclear mechanics driving the profibrotic chromatin landscape in fibrosis, highlighting actomyosin-dependent mechanisms as potential therapeutic targets in fibrosis

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)