Editorial Perspective: Speaking up for developmental language disorder - the top 10 priorities for research

Developmental language disorder (DLD) is one of the most common neurodevelopmental conditions, yet is chronically underserved, with far fewer children receiving clinical services than expected from prevalence estimates, and very little research attention relative to other neurodevelopmental conditions of similar prevalence and severity. This editorial describes a research priority-setting exercise undertaken by the Royal College of Speech and Language Therapists, which aims to redress this imbalance. From consultations with researchers, practitioners and individuals with lived experience, 10 research priorities emerge. Our goal is to share these priorities with the wider research community, to raise awareness and encourage research collaboration to improve outcomes for young people with DLD

Indicators for wild animal offtake: methods and case study for African mammals and birds

Unsustainable exploitation of wild animals is one of the greatest threats to biodiversity and to millions of people depending on wild meat for food and income. The international conservation and development community has committed to implementing plans for sustainable use of natural resources and has requested development of monitoring systems of bushmeat offtake and trade. Although offtake monitoring systems and indicators for marine species are more developed, information on harvesting terrestrial species is limited. Building on approaches developed to monitor exploitation of fisheries and population trends, we have proposed two novel indicators for harvested terrestrial species: the mean body mass indicator (MBMI) assessing whether hunters are relying increasingly on smaller species over time, as a measure of defaunation, by tracking body mass composition of harvested species within samples across various sites and dates; and the offtake pressure indicator (OPI) as a measure of harvesting pressure on groups of wild animals within a region by combining multiple time series of the number of harvested individuals across species. We applied these two indicators to recently compiled data for West and Central African mammals and birds. Our exploratory analyses show that the MBMI of harvested mammals decreased but that of birds rose between 1966/1975 and 2010. For both mammals and birds the OPI increased substantially during the observed time period. Given our results, time-series data and information collated from multiple sources are useful to investigate trends in body mass of hunted species and offtake volumes. In the absence of comprehensive monitoring systems, we suggest that the two indicators developed in our study are adequate proxies of wildlife offtake, which together with additional data can inform conservation policies and actions at regional and global scales

Mitochondrial pyruvate carrier inhibitors improve metabolic parameters in diet-induced obese mice

The mitochondrial pyruvate carrier (MPC) is an inner mitochondrial membrane complex that plays a critical role in intermediary metabolism. Inhibition of the MPC, especially in liver, may have efficacy for treating type 2 diabetes mellitus. Herein, we examined the antidiabetic effects of zaprinast and 7ACC2, small molecules which have been reported to act as MPC inhibitors. Both compounds activated a bioluminescence resonance energy transfer-based MPC reporter assay (reporter sensitive to pyruvate) and potently inhibited pyruvate-mediated respiration in isolated mitochondria. Furthermore, zaprinast and 7ACC2 acutely improved glucose tolerance in diet-induced obese mice in vivo. Although some findings were suggestive of improved insulin sensitivity, hyperinsulinemic-euglycemic clamp studies did not detect enhanced insulin action in response to 7ACC2 treatment. Rather, our data suggest acute glucose-lowering effects of MPC inhibition may be due to suppressed hepatic gluconeogenesis. Finally, we used reporter sensitive to pyruvate to screen a chemical library of drugs and identified 35 potentially novel MPC modulators. Using available evidence, we generated a pharmacophore model to prioritize which hits to pursue. Our analysis revealed carsalam and six quinolone antibiotics, as well as 7ACC1, share a common pharmacophore with 7ACC2. We validated that these compounds are novel inhibitors of the MPC and suppress hepatocyte glucose production and demonstrated that one quinolone (nalidixic acid) improved glucose tolerance in obese mice. In conclusion, these data demonstrate the feasibility of therapeutic targeting of the MPC for treating diabetes and provide scaffolds that can be used to develop potent and novel classes of MPC inhibitors

Techniques for Restoring Gorgonians to Coral Reef Injury Areas

Great attention and energy has been spent investigating reattachment techniques for dislodged and fragmented scleractinian corals; however there has been a lack of controlled experimentation on how to restore dislodged gorgonians following a disturbance event, such as a ship grounding. Unfortunately, reef damage events occur frequently off southeast Florida. As an example, since 1998 at least five freighters have grounded on the reefs near Ft. Lauderdale, Broward County. These freighters dislodged many scleractinian and gorgonian corals and often destroyed thousands of square feet of reef habitat. After these events, restoration efforts concentrated on stabilizing loose debris and rubble, and reattaching scleractinian coral fragments and dislodged colonies. Although southeast Florida’s reefs are dominated by gorgonian corals, which are also sheared from the reef when ships ground, restoration efforts generally do not place much emphasis on reattaching dislodged gorgonian colonies. In order to determine effective techniques for restoring gorgonian populations, 94 gorgonian clippings were transplanted to a reef area in Broward County, Florida in June 2004. The 15-cm clippings were cut from naturally occurring loose colonies of Pseudopterogorgia americana, Plexaura flexuosa and Muricea muricata, common gorgonians in the southeast Florida reef system. Half of these clippings were attached to the reef substrate using Portland II cement; the other half were transplanted to the reef with two-part marine epoxy. These clippings will be monitored quarterly for a minimum of one year to measure growth and health, and whether the colonies form attachments to the reef over the cement or epoxy. Clipping growth data will be compared to control, 15-20 cm naturally attached, colonies of the same species to determine whether transplant growth is similar to naturally occurring small gorgonian colonies. Data will also be collected on loose control colonies, which are tethered to small pins in the substrate. These controls will indicate whether dislodged colonies left loose on the reef will die, or whether they will reattach and continue to grow. The goal of this study is to determine effective techniques to restore gorgonian populations. This study aims to create a protocol that resource managers and scientists may follow when determining the most effective way to restore gorgonians to reef habitats following events such as ship groundings. This protocol will take into consideration the condition of each gorgonian colony and the resources available (equipment, money, and time) for restoration

Coral Reef Ecosystem Restoration Off Southeast Florida

Significant coral reef community development along the eastern shelf of the United States continues northward of the Florida Keys through Miami-Dade, Broward, Palm Beach, and Martin Counties, Florida (to Latitude 27° N). These Southeast Florida high-latitude coral communities have approximately 30 species of stony corals, stony coral coverage of 2-3%, and a diverse assemblage of reef gorgonians, sponges, and fishes. This system lays within 3 km of the coast offshore a highly urbanized area comprising a population of over 5 million people (the population of Broward County alone exceeds 1.7 million). These reefs are important economic assets: a 2001 economic assessment estimated the annual reef input for Miami-Dade, Broward, and Palm Beach Counties at 5.8 billion dollars. Potential impacts to the system include those from commercial and recreational fishing and diving, sewer outfalls, marine construction activities (fiber optic cables, channel dredging, gas pipe lines), and major shipping ports and ship groundings. Southeast Florida has three major shipping ports; Port of West Palm Beach, Port Everglades (Broward County), and the Port of Miami. At Port Everglades alone, over 5,300 ships call on an annual basis. This heavy ship traffic very near and within a coral reef system has resulted in nearly one ship grounding per year offshore Broward County since the early 1990’s. Nearly all reef damage events involve some level of injury assessment, triage and restoration, and monitoring. Triage generally involves the uprighting and caching of dislodged and fragmented stony coral colonies. At a minimum, restoration activities include the reattachment of these stony coral colonies. Restoration may also include the reattachment of dislodged octocorals and sponges and the removal of rubble generated by the damage event. This work summarizes restoration activities and monitoring results from several representative reef damage events that have occurred offshore Broward County, Florida. Discussion will include the effectiveness of past and current restoration and monitoring activities. Recommendations for improved restoration activities and more effective recovery monitoring will also be discussed

Gross genomic damage measured by DNA image cytometry independently predicts gastric cancer patient survival

BACKGROUND: DNA aneuploidy reflects gross genomic changes. It can be measured by flow cytometry (FCM-DNA) or image cytometry (ICM-DNA). In gastric cancer, the prevalence of DNA aneuploidy has been reported to range from 27 to 100%, with conflicting associations with clinicopathological variables. The aim of our study was to compare the DNA ploidy status measured using FCM-DNA and ICM-DNA in gastric cancer and to evaluate its association with clinicopathological variables. METHODS: Cell nuclei were isolated from 221 formalin-fixed, paraffin-embedded gastric cancer samples. DNA ploidy was assessed using FCM-DNA and ICM-DNA. RESULTS: A total of 178 (80.5%) gastric cancer samples were classified as DNA aneuploid using FCM-DNA, compared with 172 (77.8%) gastric cancer samples when using ICM-DNA. Results obtained from both methods were concordant in 183 (82.8%) cases (kappa = 0.48). Patients with ICM-DNA diploid gastric cancer survived significantly longer than those with ICM-DNA aneuploid gastric cancer (log rank 10.1, P = 0.001). For FCM-DNA data, this difference did not reach statistical significance. The multivariate Cox model showed that ICM-DNA ploidy status predicted patient survival independently of tumour-node-metastasis status. CONCLUSION: ICM-DNA ploidy status is an independent predictor of survival in gastric cancer patients and may therefore be a more clinically relevant read out of gross genomic damage than FCM-DNA. British Journal of Cancer (2009) 101, 1011-1018. doi:10.1038/sj.bjc.6605266 www.bjcancer.com (C) 2009 Cancer Research U