Continuous Biochemical Processing: Investigating Novel Strategies to Produce Sustainable Fuels and Pharmaceuticals

Biochemical processing methods have been targeted as one of the potential renewable strategies for producing commodities currently dominated by the petrochemical industry. To design biochemical systems with the ability to compete with petrochemical facilities, inroads are needed to transition from traditional batch methods to continuous methods. Recent advancements in the areas of process systems and biochemical engineering have provided the tools necessary to study and design these continuous biochemical systems to maximize productivity and substrate utilization while reducing capital and operating costs. The first goal of this thesis is to propose a novel strategy for the continuous biochemical production of pharmaceuticals. The structural complexity of most pharmaceutical compounds makes chemical synthesis a difficult option, facilitating the need for their biological production. To this end, a continuous, multi-feed bioreactor system composed of multiple independently controlled feeds for substrate(s) and media is proposed to freely manipulate the bioreactor dilution rate and substrate concentrations. The optimal feed flow rates are determined through the solution to an optimal control problem where the kinetic models describing the time-variant system states are used as constraints. This new bioreactor paradigm is exemplified through the batch and continuous cultivation of β-carotene, a representative product of the mevalonate pathway, using Saccharomyces cerevisiae strain mutant SM14. The second goal of this thesis is to design continuous, biochemical processes capable of economically producing alternative liquid fuels. The large-scale, continuous production of ethanol via consolidated bioprocessing (CBP) is examined. Optimal process topologies for the CBP technology selected from a superstructure considering multiple biomass feeds, chosen from those available across the United States, and multiple prospective pretreatment technologies. Similarly, the production of butanol via acetone-butanol-ethanol (ABE) fermentation is explored using process intensification to improve process productivity and profitability. To overcome the inhibitory nature of the butanol product, the multi-feed bioreactor paradigm developed for pharmaceutical production is utilized with in situ gas stripping to simultaneously provide dilution effects and selectively remove the volatile ABE components. Optimal control and process synthesis techniques are utilized to determine the benefits of gas stripping and design a butanol production process guaranteed to be profitable

Implementation of the 2017 Berlin Concussion in Sport Group Consensus Statement in contact and collision sports : a joint position statement from 11 national and international sports organisations

The 2017 Berlin Concussion in Sport Group Consensus Statement provides a global summary of best practice in concussion prevention, diagnosis and management, underpinned by systematic reviews and expert consensus. Due to their different settings and rules, individual sports need to adapt concussion guidelines according to their specific regulatory environment. At the same time, consistent application of the Berlin Consensus Statement’s themes across sporting codes is likely to facilitate superior and uniform diagnosis and management, improve concussion education and highlight collaborative research opportunities. This document summarises the approaches discussed by medical representatives from the governing bodies of 10 different contact and collision sports in Dublin, Ireland in July 2017. Those sports are: American football, Australian football, basketball, cricket, equestrian sports, football/soccer, ice hockey, rugby league, rugby union and skiing. This document had been endorsed by 11 sport governing bodies/national federations at the time of being published.http://bjsm.bmj.comhj2018Sports Medicin

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Probabilistic population forecasts for informed decision making. Letter to the Editor.

Demographic forecasts are inherently uncertain. Nevertheless, an appropriate description of this uncertainty is a key underpinning of informed decision making. In recent decades various methods have been developed to describe the uncertainty of future populations and their structures, but the uptake of such tools amongst the practitioners of official population statistics has been lagging behind. In this letter we revisit the arguments for the practical uses of uncertainty assessments in official population forecasts, and address their implications for decision making. We discuss essential challenges, both for the forecasters and forecast users, and make recommendations for the official statistics community