A new, more efficient waterwheel design for very-low-head hydropower schemes

Very-low-head hydropower constitutes a large untapped renewable energy source, estimated at 1 GW in the UK alone. A new type of low-impact waterwheel has been developed and tested at Abertay University in Scotland to improve the economic viability of such schemes. For example, on a 2·5 m high weir in the UK with 5 m3/s mean flow, one waterwheel could produce an annual investment return of 7·5% for over 100 years. This paper describes the evolution of the design and reports on scale-model tests. These show that the new design harnesses significant potential and kinetic energy to generate power and handles over four times as much water per metre width compared to traditional designs

An Exploration of the Concepts of Force and Motion in the Upper Primary Context

Students enter the science classroom having already constructed ideas about the world around them and how it functions based on their interactions with it. They do not enter the classroom as \u27empty vessels\u27. In this study, twenty one grade six students participated in focus group interviews and individual interviews based around simple demonstrations and scenarios posed on flash cards in relation to the concepts of force and motion. Seven of these students also participated in practical activity sessions centred on the inclined plane apparatus. The findings of this study suggest that the students share a number, but not all, of the conceptions about force and motion outlined in the literature, which was largely focused on secondary and tertiary-aged students. Demonstrations involving magnetism and static electricity were found to be useful for introducing the idea of a force as a push or a pull. This study suggests that the concepts of contact and non-contact forces are suitable for introduction at this stage. However, the concepts of net force and momentum were found to be too complex for students in this study. A thorough examination of the transcripts uncovered points of high productivity in the dialogue which could act as \u27signatures for cognitive growth\u27. These episodes include analogical reasoning, in-depth questioning, hypothesis generation and experimentation by the students. From the results of this study, a series of six lesson plans has been created to more effectively introduce the concepts of force and motion to upper primary school children

The Use of Magnets for Introducing Primary School Students to Some Properties of Forces Through Small-group Pedagogy

Seventeen Grade Six students were divided into small groups to study the concept of forces in the context of magnets and their properties. The researcher, a pre-service primary school teacher, encouraged the students into conversation about magnets and it was found that, without hesitation, they talked about their prior experience of magnets. The words, \u27pushing\u27 and \u27pulling\u27, endemic to an early introduction to the notion of force, were used spontaneously by the students when referring to the repulsion and attraction properties of magnets. In conversation, the students were prepared to make claims or hypotheses about magnet behaviour and often sought evidence for these. This study indicates that, given the right context, the rudimentary elements of argumentation can be appropriated naturally by children. In this paper, the focus is on the push-pull character of forces and the fact that forces appear to interact in pairs. [Author abstract

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Specifications for MSE trials for Bluefin tuna in the North Atlantic

This document is a “straw-man” draft of detailed MSE trial specifications for Bluefin tuna in the North Atlantic which, we suggest, are a desirable outcome from the ICCAT meeting on this topic to be held in Monterey over 21-23 January 2016. Such a specification document requires many decisions at a quite complex and detailed level, desirably after full discussion at the meeting. The fact that specific suggestions have been made below is not to suggest that the authors necessarily consider that those reflect the decisions which should be made. Rather their purpose is to assist clarify the totality and nature of decisions required by way of examples. Given this draft nature of this document, and its intended further development during the meeting, the text has yet to be “polished” (to include references, etc.)

Clinical utility of vinblastine therapeutic drug monitoring for the treatment of infantile myofibroma patients:A case series

Infantile myofibroma is a rare, benign tumour of infancy typically managed surgically. In a minority of cases, more aggressive disease is seen and chemotherapy with vinblastine and methotrexate may be used, although evidence for this is limited. Chemotherapy dosing in infants is challenging, and vinblastine disposition in infants is unknown. We describe the use of vinblastine therapeutic drug monitoring in four cases of infantile myofibroma. Marked inter- and intrapatient variability was observed, highlighting the poorly understood pharmacokinetics of vinblastine in children, the challenges inherent in treating neonates, and the role of adaptive dosing in optimising drug exposure in challenging situations.</p

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

Pharmacokinetics, safety and tolerability of olaparib and temozolomide for recurrent glioblastoma: results of the phase I OPARATIC trial

Background: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib potentiated radiation and temozolomide chemotherapy in pre-clinical glioblastoma models but brain penetration was poor. Clinically, PARP inhibitors exacerbate the hematological side-effects of temozolomide. The OPARATIC trial was conducted to measure penetration of recurrent glioblastoma by olaparib, and assess the safety and tolerability of its combination with temozolomide. Methods: Pre-clinical pharmacokinetic studies evaluated olaparib tissue distribution in rats and tumor-bearing mice. Adult patients with recurrent glioblastoma received various doses and schedules of olaparib and low-dose temozolomide in a 3+3 design. Suitable patients received olaparib prior to neurosurgical resection; olaparib concentrations in plasma, tumour core and tumour margin specimens were measured by mass spectrometry. A dose expansion cohort tested tolerability and efficacy of the recommended phase II dose (RP2D). Radiosensitizing effects of olaparib were measured by clonogenic survival in glioblastoma cell lines. Results: Olaparib was a substrate for multi-drug resistance protein-1 and showed no brain penetration in rats but was detected in orthotopic glioblastoma xenografts. Clinically, olaparib was detected in 71/71 tumor core specimens (27 patients, median 496nM) and 21/21 tumor margin specimens (9 patients, median 512.3nM). Olaparib exacerbated TMZ-related hematological toxicity, necessitating intermittent dosing. RP2D was olaparib 150mg (3 days/week) with TMZ 75mg/m2 daily for 42 days. Fourteen (36%) of 39 evaluable patients were progression-free at 6 months. Olaparib radiosensitized six glioblastoma cell lines at clinically relevant concentrations of 100 and 500 nM. Conclusions: Olaparib reliably penetrates recurrent glioblastoma at radiosensitizing concentrations, supporting further clinical development and highlighting the need for better pre-clinical models

Nontuberculous Mycobacteria–associated Lung Disease in Hospitalized Persons, United States, 1998–2005

This bacterium is an underappreciated cause of lung disease and infection rates appear to be increasing