Optimal sampling locations to reduce uncertainty in contamination extent in water distribution systems.

Drinking water utilities rely on samples collected from the distribution system to provide assurance of water quality. If a water contamination incident is suspected, samples can be used to determine the source and extent of contamination. By determining the extent of contamination, the percentage of the population exposed to contamination, or areas of the system unaffected can be identified. Using water distribution system models for this purpose poses a challenge because significant uncertainty exists in the contamination scenarios (e.g., injection location, amount, duration, customer demands, contaminant characteristics). This article outlines an optimization framework to identify strategic sampling locations in water distribution systems. The framework seeks to identify the best sampling locations to quickly determine the extent of the contamination while considering uncertainty with respect to the contamination scenarios. The optimization formulations presented here solve for multiple optimal sampling locations simultaneously and efficiently, even for large systems with a large uncertainty space. These features are demonstrated in two case studies.

AAGBI: Safer pre-hospital anaesthesia 2017: Association of Anaesthetists of Great Britain and Ireland.

Pre-hospital emergency anaesthesia with oral tracheal intubation is the technique of choice for trauma patients who cannot maintain their airway or achieve adequate ventilation. It should be carried out as soon as safely possible, and performed to the same standards as in-hospital emergency anaesthesia. It should only be conducted within organisations with comprehensive clinical governance arrangements. Techniques should be straightforward, reproducible, as simple as possible and supported by the use of checklists. Monitoring and equipment should meet in-hospital anaesthesia standards. Practitioners need to be competent in the provision of in-hospital emergency anaesthesia and have supervised pre-hospital experience before carrying out pre-hospital emergency anaesthesia. Training programmes allowing the safe delivery of pre-hospital emergency anaesthesia by non-physicians do not currently exist in the UK. Where pre-hospital emergency anaesthesia skills are not available, oxygenation and ventilation should be maintained with the use of second-generation supraglottic airways in patients without airway reflexes, or basic airway manoeuvres and basic airway adjuncts in patients with intact airway reflexes.

Farmers' beliefs about bovine tuberculosis control in Northern Ireland.

Beliefs can play an important role in farmer behaviour and willingness to adopt new policies. In Northern Ireland, bovine tuberculosis (bTB) is one of the most important endemic diseases facing the cattle industry. An observational study was conducted on 192 farms in a high bTB incidence area during 2010-2011 in order to obtain a better understanding of farmers' beliefs in relation to bTB control. The views of farmers who had experienced a recent confirmed or multiple reactor bTB breakdowns (cases) were compared to those of farmers who had no recent reactors or restricted herd tests (controls). Data were obtained from a face-to-face questionnaire assessing farmers' agreement to 22 statements. All participating farmers found bTB control important and most were keen to learn more about bTB biosecurity measures and were in favour of the cattle-related bTB control measures as presented in the questionnaire (isolation of skin test inconclusive animals, use of the gamma-interferon test and pre-movement testing). The majority of farmers would allow badger vaccination and culling on their own land with an overall preference for vaccination. Highest disagreement was shown for the statements querying a willingness to pay for bTB control measures. There was agreement on most issues between case and control farmers and between different age groups of farmers although case farmers showed more support for additional advice on bTB biosecurity measures (P = 0.042). Case farmers were also more in favour of allowing badger vaccination (P = 0.008) and culling (P = 0.043) on their land and showed less concern for public opposition (P = 0.048).

Herd-level risk factors for bovine tuberculosis and adoption of related biosecurity measures in Northern Ireland: A case-control study.

Bovine tuberculosis (bTB) is a zoonotic disease which is endemic in Northern Ireland. As it has proven difficult to eradicate this disease, partly due to a wildlife reservoir being present in the European badger (Meles meles), a case-control study was conducted in a high incidence area in 2010-2011. The aim was to identify risk factors for bTB breakdown relating to cattle and badgers, and to assess the adoption of bTB related biosecurity measures on farms. Face-to-face questionnaires with farmers and surveys of badger setts and farm boundaries were conducted on 117 farms with a recent bTB breakdown (cases) and 75 farms without a recent breakdown (controls). On logistic regression at univariable and multivariable levels, significant risk factors associated with being a case herd included having an accessible badger sett within the farm boundaries in a field grazed in the last year (odds ratio, OR, 4.14; 95% confidence interval, CI, 1.79, 9.55), observation of live badgers (OR 4.14; 95% CI 1.79, 9.55), purchase of beef cattle (OR 4.60; 95% CI 1.61, 13.13), use of contractors to spread slurry (OR 2.83; 95% CI 1.24, 6.49), feeding meal on top of silage (OR 3.55; 95% CI 1.53, 8.23) and feeding magnesium supplement (OR = 3.77; 95% CI 1.39, 10.17). The majority of setts within the farm boundary were stated to be accessible by cattle (77.1%; 95% CI 71.2, 83.0%) and 66.8% (95% CI 63.8, 69.7%) of farm boundaries provided opportunities for nose-to-nose contact between cattle. Adoption of bTB related biosecurity measures, especially with regards to purchasing cattle and badger-related measures, was lower than measures related to disinfection and washing.

A survey of surgical airway experiences and equipment among immediate care doctors.

BACKGROUND: There is a variety of approaches to obtaining a surgical airway, but little literature on techniques other than surgical cricothyroidotomy and the placement of a cuffed tube. METHODS: An e-mail and postal survey of the memberships of the British Association for Immediate Care (BASICS) and BASICS (Scotland) was performed to ascertain the equipment carried for a surgical airway and obtain summarised case reports of the surgical airways performed. RESULTS: The response rate was 359 of 942 surveys sent (38%). Most doctors carry equipment to perform a surgical airway. A total of 93 prehospital surgical airways was reported as summarised cases. A needle cricothyroidotomy was initially obtained in 17 cases (18%) but was changed to other types in all but six cases. Of these six patients, two survived to hospital. A small uncuffed tube was initially placed in 29 patients (31%) and remained in 23 cases; 22 survived to hospital. A surgical cricothyroidotomy and placement of a cuffed tube was the initial airway obtained in 51 cases and the final airway obtained in 64 (69%) patients; 34 survived to reach hospital. Some spontaneous ventilation remained in 56 (60%) patients. CONCLUSIONS: This paper reports the successful prehospital use of small uncuffed tubes in both breathing and apnoeic patients. The survival rate to hospital following a prehospital surgical airway is reasonable. There is a high incidence of spontaneous ventilation in this patient cohort. There were a number of limitations with this study, but the subject is worthy of further research.

Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection.

Estrogen reduces brain injury after experimental cerebral ischemia in part through a genomic mechanism of action. Using DNA microarrays, we analyzed the genomic response of the brain to estradiol, and we identified a transcript, cocaine- and amphetamine-regulated transcript (CART), that is highly induced in the cerebral cortex by estradiol under ischemic conditions. Using in vitro and in vivo models of neural injury, we confirmed and characterized CART mRNA and protein up-regulation by estradiol in surviving neurons, and we demonstrated that i.v. administration of a rat CART peptide is protective against ischemic brain injury in vivo. We further demonstrated binding of cAMP response element (CRE)-binding protein to a CART promoter CRE site in ischemic brain and rapid activation by CART of ERK in primary cultured cortical neurons. The findings suggest that CART is an important player in estrogen-mediated neuroprotection and a potential therapeutic agent for stroke and other neurodegenerative diseases.

Multiple pathways transmit neuroprotective effects of gonadal steroids.

Numerous preclinical studies suggest that gonadal steroids, particularly estrogen, may be neuroprotective against insult or disease progression. This paper reviews the mechanisms contributing to estrogen-mediated neuroprotection. Rapid signaling pathways, such as MAPK, PI3K, Akt, and PKC, are required for estrogen's ability to provide neuroprotection. These rapid signaling pathways converge on genomic pathways to modulate transcription of E2-responsive genes via ERE-dependent and ERE-independent mechanisms. It is clear that both rapid signaling and transcription are important for estrogen's neuroprotective effects. A mechanistic understanding of estrogen-mediated neuroprotection is crucial for the development of therapeutic interventions that enhance quality of life without deleterious side effects.

Sandwich ELISA detection of Clostridium perfringens cells and alpha-toxin from field cases of necrotic enteritis of poultry.

Sandwich ELISAs (sELISAs) for the detection of Clostridium perfringens cells and alpha-toxin were developed and used to screen intestinal samples from normal broiler chickens and from clinical cases of necrotic enteritis. The assays clearly distinguished between the two sets of samples. The sELISA absorbance values from samples obtained from the majority of healthy birds were low and those from the majority of necrotic enteritis cases were high. Together, the assays provide a suitable test for the rapid screening for the diagnosis of necrotic enteritis in poultry.

Dishevelled activates Ca2+ flux, PKC, and CamKII in vertebrate embryos.

Wnt ligands and Frizzled (Fz) receptors have been shown to activate multiple intracellular signaling pathways. Activation of the Wnt-beta-catenin pathway has been described in greatest detail, but it has been reported that Wnts and Fzs also activate vertebrate planar cell polarity (PCP) and Wnt-Ca2+ pathways. Although the intracellular protein Dishevelled (Dsh) plays a dual role in both the Wnt-beta-catenin and the PCP pathways, its potential involvement in the Wnt-Ca2+ pathway has not been investigated. Here we show that a Dsh deletion construct, XDshDeltaDIX, which is sufficient for activation of the PCP pathway, is also sufficient for activation of three effectors of the Wnt-Ca2+ pathway: Ca2+ flux, PKC, and calcium/calmodulin-dependent protein kinase II (CamKII). Furthermore, we find that interfering with endogenous Dsh function reduces the activation of PKC by Xfz7 and interferes with normal heart development. These data suggest that the Wnt-Ca2+ pathway utilizes Dsh, thereby implicating Dsh as a component of all reported Fz signaling pathways.

Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Loci associated with FEVR map to 11q13-q23 (EVR1; OMIM 133780, ref. 1), Xp11.4 (EVR2; OMIM 305390, ref. 2) and 11p13-12 (EVR3; OMIM 605750, ref. 3). Here we have confirmed linkage to the 11q13-23 locus for autosomal dominant FEVR in one large multigenerational family and refined the disease locus to a genomic region spanning 1.55 Mb. Mutations in FZD4, encoding the putative Wnt receptor frizzled-4, segregated completely with affected individuals in the family and were detected in affected individuals from an additional unrelated family, but not in normal controls. FZD genes encode Wnt receptors, which are implicated in development and carcinogenesis. Injection of wildtype and mutated FZD4 into Xenopus laevis embryos revealed that wildtype, but not mutant, frizzled-4 activated calcium/calmodulin-dependent protein kinase II (CAMKII) and protein kinase C (PKC), components of the Wnt/Ca(2+) signaling pathway. In one of the mutants, altered subcellular trafficking led to defective signaling. These findings support a function for frizzled-4 in retinal angiogenesis and establish the first association between a Wnt receptor and human disease.

Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation.

Dapper was isolated in a screen for proteins interacting with Dishevelled, a key factor in Wnt signaling. Dapper and Dishevelled colocalize intracellularly and form a complex with Axin, GSK-3, CKI, and beta-catenin. Overexpression of Dapper increases Axin and GSK-3 in this complex, resulting in decreased soluble beta-catenin and decreased activation of beta-catenin-responsive genes. Dapper also inhibits activation by Dishevelled of c-Jun N-terminal kinase (JNK), a component of beta-catenin-independent Frizzled signaling. Inhibition of Dapper activates both beta-catenin-responsive genes and an AP1-responsive promoter, demonstrating that Dapper is a general Dishevelled antagonist. Depletion of maternal Dapper RNA from Xenopus embryos results in loss of notochord and head structures, demonstrating that Dapper is required for normal vertebrate development.

A transgenic Lef1/beta-catenin-dependent reporter is expressed in spatially restricted domains throughout zebrafish development.

The Wnt/beta-catenin signaling pathway plays multiple roles during embryonic development, only a few of which have been extensively characterized. Although domains of Wnt expression have been identified throughout embryogenesis, anatomical and molecular characterization of responding cells has been mostly unexplored. We have generated a transgenic zebrafish line that expresses a destabilized green fluorescent protein (GFP) variant under the control of a beta-catenin responsive promoter. Early zygotic expression of this transgene (TOPdGFP) mirrors known domains of Wnt signaling in the embryo. Loss of Lef1 activity results in decreased reporter expression and posterior defects, while loss of Tcf3 (Headless, Hdl) activity does not alter reporter expression, even though it results in loss of forebrain structures. In addition, ectopic Wnt1 expression can activate the reporter. In older embryos, we identify a number of transgene-expressing cell populations as novel sites of beta-catenin signaling. We conclude that our TOP-dGFP reporter line faithfully illustrates domains of beta-catenin activity and enables the identification of responsive cell populations.