Altran (United Kingdom)

Iron can accumulate in the body due to several causes, resulting in iron overload syndrome. The most common cause is hereditary haemochromatosis (HH), a genetic disorder triggered by inactivation of the iron hormone hepcidin, which results in hyperferraemia and excessive tissue iron deposition. Other causes include repeated blood transfusion, iron-loading anaemias and some chronic liver diseases. Left undiagnosed, HH can cause significant damage to the liver, heart, pancreas and joints, because excess iron is toxic. This also increases the risk of hepatocellular carcinoma, especially in those with cirrhosis of the liver, with an estimate of 1 in 10 HH patients affected. The risk of developing type 2 diabetes is increased by 2.5-7.1 times compared with non-diabetic patients. Haemochromatosis is usually considered when elevated serum ferritin and transferrin saturation levels are found. Ferritin in excess of 300 ng/mL usually indicates iron overload. Genetic testing can identify the two most common mutations in the HFE gene - a positive result confirms the diagnosis of haemochromatosis - but there are also rare forms of the disease unrelated to HFE mutations. Liver biopsy can be used to ascertain iron accumulation and histological presence of fibrosis (cirrhosis). Assessment of the hepatic iron index is considered the gold standard for diagnosis of haemochromatosis. Magnetic resonance imaging has been used as a non-invasive alternative to accurately estimate iron deposition levels in the liver, heart, joints and pituitary gland. Population screening is not recommended; however, family members of identified people should be screened to determine their phenotypic or carrier potential. Early diagnosis enables preventative measures to be commenced. Routine treatment is by regular venesection of 500 mL of whole blood per session. An initiation phase of weekly or twice-weekly venesection is common until serum ferritin (SF) is reduced to normal. When SF and other markers are within normal range, regular venesections are usually scheduled 1-3 months apart, depending on the underlying cause and SF response. Dietary iron including red meat and fortified foods such as cereals should be avoided. Vitamin C promotes iron absorption, and supplementation should be avoided, as should alcohol, which can increase the risk of concomitant liver disease. John's story outlines a typical journey through diagnosis, treatment and care during HH while living on Arran, an island off the coast of Scotland. Subsequently, John developed hepatocellular carcinoma, and his treatment and palliative care are described. We wrote this article to give the reader an insight to this silent disorder and the value of recognising the signs and symptoms for early diagnosis and subsequent treatment.

We present the first steps of a broad effort to develop a formal representation of SPARK 2014 suitable for supporting machine-verified static analyses and translations. In our initial work, we have developed technology for translating the GNAT compiler's abstract syntax trees into the Coq proof assistant, and we have formalized in Coq the dynamic semantics for a toy subset of the SPARK 2014 language. SPARK 2014 programs must ensure the absence of certain run-time errors (for example, those arising while performing division by zero, accessing non existing array cells, overflow on integer computation). The main novelty in our semantics is the encoding of (a small part of) the run-time checks performed by the compiler to ensure that any well-formed terminating SPARK programs do not lead to erroneous execution. This and other results are mechanically proved using the Coq proof assistant. The modeling of on-the-fly run-time checks within the semantics lays the foundation for future work on mechanical reasoning about SPARK 2014 program correctness (in the particular area of robustness) and for studying the correctness of compiler optimizations concerning run-time checks, among others.

The interaction of multiple domains, the evolving technologies and the relative lack of experience with respect to conventional vehicle development, compounds the complexities within the hybrid electric vehicle (HEV) design space. In order to meet the needs of efficient and flexible HEV powertrain modelling within this design space, a parallel is drawn with the development of complex software systems. This paper proposes a modelling method that makes use of object-oriented modelling principles for the design and development of HEV powertrain models. A case study shows how the method is used in developing a library of reusable, replaceable and maintainable models for HEV powertrain modelling.

This paper describes SPARKSkein - a new reference implementation of the Skein cryptographic hash algorithm, written and verified using the SPARK language and toolset. The new implementation is readable, completely portable to a wide-variety of machines of differing word-sizes and endian-ness, and “formal” in that it is subject to a proof of type safety. This proof also identified a subtle bug in the original reference implementation which persists in the C version of the code. Performance testing has been carried out using three generations of the GCC compiler. With the latest compiler, the SPARK code offers identical performance to the existing C reference implementation. As a further result of this work, we have identified several opportunities to improve both the SPARK tools and GCC.

The generation of a thick fully turbulent boundary layer is investigated in a lowspeed wind tunnel at a nominal zero pressure gradient over the Reynolds number range 0.145× 10 6 · Rex · 0.58× 10 6 . The wind tunnel floor natural boundary layer is laminar with thickness ± between 5.76 mm and 8.13 mm. Different tripping devices are tested to trigger transition so to double the boundary layer thickness and provide a fully established turbulent velocity profile. Using a trip wire significantly increases ± but leads to an unsatisfactory velocity profile. Using a sandpaper strip slightly increases ± but keeps the boundary layer laminar. Using a strip of sharp-edged silicon granules doubles the boundary layer thickness that increases up to 20 mm and the mean velocity profiles are a good fit to the logarithmic law of the wall over the outer region of the boundary layer. The spectral decay of turbulent kinetic energy in this outer layer is exponential and close to i5/3, indicating turbulence equilibrium. This work is of practical interest to wind tunnel practitioners for generating equilibrium thick turbulent boundary layers at low Reynolds numbers.