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Anxiety before dental procedures is common in children, and is usually managed by conscious sedation of the patient. Previously, nitrous oxide inhalation was the only method widely used in primary care, so patients who could not be thus sedated were referred for general anaesthesia. In 2010, NICE published the first national guideline on medical sedation, which states that administration of midazolam should be considered alongside the standard technique of nitrous oxide inhalation for sedation of children. That recommendation is based on robust evidence, the majority of which came from a series of randomised controlled clinical trials carried out by researchers at Newcastle University. Midazolam is now deployed as a second-line sedation option across the UK.
The way in which UK upland hay meadows are managed and restored to conserve botanical diversity has been largely determined by research carried out at Newcastle University. Increased post-war agricultural production has converted most species-rich upland hay meadows to species- poor rye-grass grassland so that today only 1070 ha (hectares) undisturbed hay meadow remains. The Newcastle research has been used by Natural England (an executive non-departmental public body responsible for England's natural environment) to produce targeted management prescriptions for 2500 ha of farmland in northern England and has informed National Park and AONB (Area of Outstanding Natural Beauty) management on best practice for successful restoration of hay meadows. The research has ensured the successful restoration of more than half of the remaining upland hay meadows in England.
Through their study of DNA polymerases from organisms of the domain archaea, researchers at Newcastle University and University College London identified the mechanism by which these organisms avoid potentially damaging mutations in their DNA. As a consequence of this work they invented a novel genetically-engineered DNA polymerase. This enzyme has been patented and is the world's only high-fidelity, proofreading DNA polymerase that efficiently reads through uracil in the polymerase chain reaction (PCR). PCR is a very widely used technique in biomedical research. An international bioscience company [Text removed for publication, EV d] signed a licensing agreement with Newcastle University in 2008 to market the enzyme, and total sales since 2008 exceed [Text removed for publication, EV d]. Further commercial exploitation has begun through licensing agreements with other major companies.
Newcastle University research has made significant contributions to international best practice guidelines used to restore coral reefs. Coral reefs are the most biologically diverse eco-systems on earth, directly and indirectly providing an estimated $375 billion per year in ecosystem services. Despite their importance, very little work had been undertaken to assess the strategies used to rehabilitate damaged reefs prior to the Newcastle research. Research findings have subsequently been incorporated into international best practice guidelines which are used by a diverse group of users including reef managers who use them to plan more ecologically robust reefs and maritime insurers who use them to assess insurance claims related to reef damage by grounded ships.
Chronic granulomatous disease is a rare but very serious inherited disorder of the immune system that leaves sufferers vulnerable to potentially fatal bacterial and fungal infections. Researchers at Newcastle University demonstrated very high survival and cure rates following bone marrow transplantation for the disease and good quality of life for successfully transplanted patients. This led to a change in national clinical policy, and doctors at both specialist disease centres in the UK now recommend transplantation to families where previously they would not have done so. In the five years prior to 2008 there were only 11 transplants for chronic granulomatous disease in the UK and in the following five years, 36 transplants. 32 children are alive and cured of the disease.
Warfarin is an anti-coagulant drug prescribed to tens of millions of people in the UK and US who are at high risk of developing blood clots. Because individual sensitivity to warfarin varies in the population there is a risk of overdosing the drug and causing serious bleeding and even stroke in many people when starting treatment. In 1999 researchers at Newcastle University were the first to demonstrate a statistically significant link between a person's genotype and the appropriate dose of warfarin. In 2010 the US Food and Drug Administration (FDA) mandated inclusion of a table of dose recommendations based on genotype in the warfarin prescribing information leaflet accompanying the drug. Newcastle research forms the basis of the 2009 international standard algorithm for gene-guided dosing of warfarin. This approach has been adopted by large US medical centres and the FDA states that it will prevent 17,000 strokes a year in the US.
Dementia is one of the greatest problems facing society today, both in financial terms and in terms of the quality of life of patients and caregivers. Newcastle research identified that cholinesterase inhibitors (CHEIs), originally licenced for use in Alzheimer's disease, would be of greater benefit in two other types of dementia; Lewy body dementia and Parkinson's disease. CHEIs are now recommended in national and international guidelines as a treatment for the cognitive and psychiatric symptoms associated with both of these conditions, which previously had no effective treatment. CHEIs are also licenced worldwide for use in Parkinson's dementia, and are used off- licence across the world as a first-line treatment for dementia with Lewy bodies.
Newcastle University research discovered the first potent inhibitors of the DNA repair enzyme poly (ADP-ribose) polymerase 1 (PARP-1) through medicinal chemistry and preclinical work leading to first-in-man clinical studies. This research led to the development of Rucaparib, an agent that inhibits the ability of cancer cells to survive drug treatments or radiotherapy. As a result of Newcastle's research a further 8 PARP inhibitors are in development. Major pharmaceutical companies have invested an estimated $385 million in clinical trials, with at least 7000 patients enrolled in PARP inhibitor trials since 2008. Cancer patients worldwide have already been successfully treated with these new anti-cancer drugs.
Congenital myasthenic syndromes (CMS) are inherited neuromuscular disorders caused by defects at neuromuscular junctions, which are often a result of acetylcholine receptor gene mutations. A subset of CMS patients (around 14% in the US and Europe) have limb-girdle myasthenia (LGM). This disease can be highly disabling with symptoms including increasing weakness of skeletal muscles. As a result of collaborative work between Newcastle and Oxford, it was determined that many LGM patients have a mutation of the Dok-7 gene (unrelated to the acetylholine receptor), and do not, therefore, respond to standard CMS treatments. Since then, a number of additional mutations have been discovered, and genetic testing is now available for the majority of known LGM-causative genes. Crucially, Dok-7 patients, and those with other non-receptor related mutations, can now be diagnosed accurately and treated effectively, with ephedrine and salbutamol (in the US, albuterol). This significantly improves these patients' quality of life by enabling them to walk and breathe unassisted.
Limb-girdle muscular dystrophy type 2A is a rare (about six cases per million individuals) and incurable muscular disorder with a genetic basis. Although diagnosis is a multi-step process, which includes symptom assessment and histopathology of affected muscle, it invariably involves measurement of the amount of protein calpain 3 in muscle biopsy samples. This is performed in diagnostic laboratories worldwide using the two monoclonal antibodies CALP-12A2 and CALP-2C4, which were developed by researchers at Newcastle University in the late 1990s. In 2009 Newcastle University signed a licensing agreement with the international bioscience company Leica Biosystems that currently sells the antibodies to institutions worldwide.