A bottom-up approach to identifying the maximum operational adaptive capacity of water resource systems to a changing climate

Many water resource systems have been designed assuming that the statistical characteristics of future inflows are similar to those of the historical record. This assumption is no longer valid due to large-scale changes in the global climate, potentially causing declines in water resource system performance, or even complete system failure. Upgrading system infrastructure to cope with climate change can require substantial financial outlay, so it might be preferable to optimize existing system performance when possible. This paper builds on decision scaling theory by proposing a bottom-up approach to designing optimal feedback control policies for a water system exposed to a changing climate. This approach not only describes optimal operational policies for a range of potential climatic changes but also enables an assessment of a system's upper limit of its operational adaptive capacity, beyond which upgrades to infrastructure become unavoidable. The approach is illustrated using the Lake Como system in Northern Italy—a regulated system with a complex relationship between climate and system performance. By optimizing system operation under different hydrometeorological states, it is shown that the system can continue to meet its minimum performance requirements for more than three times as many states as it can under current operations. Importantly, a single management policy, no matter how robust, cannot fully utilize existing infrastructure as effectively as an ensemble of flexible management policies that are updated as the climate changes

Investigating the prevalence of Salmonella in dogs within the Midlands region of the United Kingdom

Background - The intimate relationship between dogs and their owners has the potential to increase the risk of human exposure to bacterial pathogens. Over the past 40 years, there have been several reports on transmission of salmonellae from dogs to humans. This study therefore aimed to determine the prevalence of Salmonella in the faeces of dogs from the Midlands region of the United Kingdom to assess exposure risk and potential for zoonotic transmission. Results - A total of 436 apparently healthy dogs without diarrhoea from households (n = 126), rescue centres (n = 96), boarding kennels (n = 43), retired greyhound kennels (n = 39) and a pet nutrition facility (n = 132) were investigated for Salmonella shedding. Faecal samples were processed by an enrichment culture based method. The faeces from one dog (0.23 %; 95 % confidence limit 0.006 %, 1.27 %) was positive for Salmonella. The species was S. enterica subspecies arizonae. Conclusion - This study showed that the prevalence of Salmonella from faeces from apparently healthy dogs from a variety of housing conditions is low; however, Salmonella shedding was still identified

The early mathematical education of Ada Lovelace

Ada, Countess of Lovelace, is remembered for a paper published in 1843, which translated and considerably extended an article about the unbuilt Analytical Engine, a general-purpose computer designed by the mathematician and inventor Charles Babbage. Her substantial appendices, nearly twice the length of the original work, contain an account of the principles of the machine, along with a table often described as ‘the first computer program’. In this paper we look at Lovelace's education before 1840, which encompassed older traditions of practical geometry; newer textbooks influenced by continental approaches; wide reading; and a fascination with machinery. We also challenge judgements by Dorothy Stein and by Doron Swade of Lovelace's mathematical knowledge and skills before 1840, which have impacted later scholarly and popular discourse

Screening for clinically significant non-deletional alpha thalassaemia mutations by pyrosequencing.

Non-deletional α(+)-thalassaemia is associated with a higher degree of morbidity and mortality than deletional forms of α(+)-thalassaemia. Screening for the common deletional forms of α-thalassaemia by Gap-PCR is widely practiced; however, the detection of non-deletional α-thalassaemia mutations is technically more labour-intensive and expensive, as it requires DNA sequencing. In addition, the presence of four very closely homologous alpha globin genes and the frequent co-existence of deletional forms of α-thalassaemia present another layer of complexity in the detection of these mutations. With growing evidence that non-deletional α-thalassaemia is relatively common in the UK, there is a demand for technologies which can quickly and accurately screen for these mutations. We describe a method utilising pyrosequencing for detecting the ten most common clinically significant non-deletional α-thalassaemia mutations in the UK. We tested 105 patients with non-deletional α-thalassaemia and found 100% concordance with known genotype as identified by Sanger sequencing. We found pyrosequencing to be simpler, more robust, quicker, and cheaper than conventional sequencing, making it a good choice for rapid and cost-effective diagnosis of patients with suspected non-deletional α-thalassaemia. The technique is also likely to help expedite prenatal diagnosis of pregnancies at risk of α-thalassaemia major

Haemoglobin (Hb) G-Philadelphia, Hb Stanleyville-II, Hb G-Norfolk, Hb Matsue-Oki and Hb Mizushi can form a panel of α-chain variants that overlap in their phenotype: the novel use of StyI to screen for Hb G-Philadelphia.

INTRODUCTION: Haemoglobin (Hb) G-Philadelphia mutation is a common alpha-globin chain variant [α68(E17)Asn > Lys]. Combined high performance liquid chromatography (HPLC) and isoelectric focusing (IEF) can be used in a presumptive diagnosis of Hb G-Philadelphia, but there are other α-chain variants with a similar phenotype that cannot be excluded. Our aim was to develop a novel StyI restriction enzyme assay to diagnose the common Hb G-Philadelphia mutation and to identify any other variants with a similar phenotype by DNA sequencing. METHODS: Thirty-one cases given a presumptive diagnosis as Hb G-Philadelphia by HPLC and IEF were subjected to DNA analysis by restriction enzyme digestion using StyI. Negative cases were then subjected to DNA sequencing. RESULTS: Twenty-two cases (78.6%) of 28 cases amplified were tested positive for Hb G-Philadelphia by StyI restriction digestion. Sequencing of the six negative cases revealed two cases of Hb G-Philadelphia with C→A mutation in codon 68 in α2 globin gene, plus one case each of Hb G-Norfolk Hb Stanleyville-II, Hb Matsue-Oki and Hb Mizushi. CONCLUSION: A novel StyI restriction enzyme can be used to confirm the commonest type of Hb G-Philadelphia. DNA sequencing identified four other α-chain variants with a similar HPLC and IEF phenotype

A study of δ-globin gene mutations in the UK population: identification of three novel variants and development of a novel DNA test for Hb A'2.

We report here the spectrum of δ-globin gene mutations found in the UK population. Nine different δ chain variants and two δ-thalassemia (δ-thal) mutations were characterized in a study of 127 alleles in patients with either a low Hb A2 value or a split Hb A2 peak on high performance liquid chromatography (HPLC). The most common δ chain variant was Hb [Formula: see text] (or Hb B2) [δ16(A13)Gly → Arg; HBD: c.49G > C] (77.0%), followed by Hb A2-Yialousa [δ27(B9)Ala → Ser; HBD: c.82G > T] (12.0%), Hb A2-Babinga [δ136(H14)Gly → Asp; HBD: c.410G > A] (3.0%), Hb A2-Troodos [δ116(G18)Arg → Cys; HBD: c.349C > T] (1.0%), Hb A2-Coburg [δ116(G18)Arg → His; HBD: c.350G > A] (2.0%) and Hb A2-Indonesia [δ69(E13)Gly → Arg; HBD: c.208G > C] (1.0%). Three novel variants were identified: Hb A2-Calderdale [codon 2 (CAT > AAT), His → Asn; HBD: c.7C > A], Hb A2-Walsgrave [codon 52 (GAT > CAT), Asp → His; HBD: c.157G > C] and Hb A2-St. George's [codon 81 (CTC > TTC), Leu → Phe; HBD: c.244C > T]. In addition, two known δ-thal mutations were observed: -68 (C > T); HBD: c.-118C > T and codon 4 (ACT > ATT); HBD: c.14C > T. Amplification refractory mutation system (ARMS) primers were developed to provide a simple molecular diagnostic test for the most common variant, Hb [Formula: see text]. Three of the variants had a characteristic HPLC retention time that can be used for a presumptive diagnosis

A bottom-up approach to identifying the maximum operational adaptive capacity of water resource systems to a changing climate

Many water resource systems have been designed assuming that the statistical characteristics of future inflows are similar to those of the historical record. This assumption is no longer valid due to large-scale changes in the global climate, potentially causing declines in water resource system performance, or even complete system failure. Upgrading system infrastructure to cope with climate change can require substantial financial outlay, so it might be preferable to optimize existing system performance when possible. This paper builds on decision scaling theory by proposing a bottom-up approach to designing optimal feedback control policies for a water system exposed to a changing climate. This approach not only describes optimal operational policies for a range of potential climatic changes but also enables an assessment of a system's upper limit of its operational adaptive capacity, beyond which upgrades to infrastructure become unavoidable. The approach is illustrated using the Lake Como system in Northern Italy—a regulated system with a complex relationship between climate and system performance. By optimizing system operation under different hydrometeorological states, it is shown that the system can continue to meet its minimum performance requirements for more than three times as many states as it can under current operations. Importantly, a single management policy, no matter how robust, cannot fully utilize existing infrastructure as effectively as an ensemble of flexible management policies that are updated as the climate changes.S. Culley, S. Noble, A. Yates, M. Timbs, S. Westra, H. R. Maier, M. Giuliani, and A. Castellett