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To examine geriatric classification as a predictor of survival in moderate to severely injured dogs denoted by animal trauma triage (ATT) scores ≥3 or modified Glasgow Coma Scale (mGCS) scores ≤14.Retrospective observational cohort study utilizing data collected between September 2013 and May 2019 with follow-up until death or hospital discharge.Thirty-one trauma centers including university teaching hospitals and private referral centers.A total of 6169 dogs entered into the Veterinary Committee on Trauma Registry with complete data entry including age, weight, outcome, mGCS (≤14), and/or ATT (≥3).None.The effect of geriatric classification on survival was estimated using shared-frailty cox proportional hazard models. Model 1 dependent variables: death despite intervention or euthanasia due to grave prognosis. Model 2 dependent variables: death by euthanasia due to financial influence or combined influence of finances and grave prognosis. Model 3 evaluated interactions between geriatric classification and moderate versus severe trauma. The shared-frailty models controlled for contributing site as a random effect and other confounding variables, including trauma severity. Model 1: geriatrics had a significantly increased hazard risk (HR) for death (HR = 1.48, P 0.0001). Model 2: geriatrics had an insignificant increased HR for death (HR = 1.34, P = 0.08). Model 3: geriatrics demonstrated significantly increased mortality risk with moderate level trauma. Additional Model 1 variables independently associated with mortality include ATT perfusion, neurologic, respiratory subscores, mGCS motor subscore, weight, and spinal trauma. Additional Model 2 variables independently associated with mortality include ATT perfusion subscore and neuter status. In general, statistical differences between cohorts were found with regard to lactate, PCV, total protein, and glucose.Among moderately injured dogs who experienced death despite intervention or euthanasia due to grave prognosis, mortality risk is significantly higher in geriatrics as compared to nongeriatrics.

In the interpretation of the rising in 1520 of the Comunidades de Castilla, the tendency has been to view the events within the framework of a stratification in Castilian society, real or imagined. Analysis of some flashpoints of insurgency, in particular Zamora, Murcia, Requena, Cuenca, Plasencia, Baeza and others, has shown that, whoever was involved in street skirmishes, the protagonists were often influenced and even supported by the same vested interests from elsewhere, apprehensive of the prospect of losing control of economic resources.

BACKGROUND Improving the assessment and training of tracheal intubation is hindered by the lack of a sufficiently validated profile of expertise. Although several studies have examined biomechanics of tracheal intubation, there are significant gaps in the literature. We used 3-dimensional motion capture to study pediatric providers performing simulated tracheal intubation to identify candidate kinematic variables for inclusion in an expert movement profile. METHODS Pediatric anesthesiologists (experienced) and pediatric residents (novices) were recruited from a pediatric institution to perform tracheal intubation on airway mannequins in a motion capture laboratory. Subjects performed 21 trials of tracheal intubation, 3 each of 7 combinations of laryngoscopic visualization (direct or indirect), blade type (straight or curved), and mannequin size (adult or pediatric). We used repeated measures analysis of variance to determine whether various kinematic variables (3-trial average for each participant) were associated with experience. RESULTS Eleven experienced and 15 novice providers performed 567 successful tracheal intubation attempts (9 attempts unsuccessful). For laryngoscopy, experienced providers exhibited shorter path length (total distance traveled by laryngoscope handle; 77.6 ± 26.0 cm versus 113.9 ± 53.7 cm; P = 0.013) and greater angular variability at the left wrist (7.4 degrees versus 5.5 degrees, P = 0.013) and the left elbow (10.1 degrees versus 7.6 degrees, P = 0.03). For intubation, experienced providers exhibited shorter path length of the right hand (mean = 61.1 cm versus 99.9 cm, P < 0.001), lower maximum acceleration of the right hand (0.19 versus 0.14 m/s, P = 0.033), and smaller angular, variability at the right elbow (9.7 degrees versus 7.9 degrees, P = 0.03). CONCLUSIONS Our study and the available literature suggest specific kinematic variables for inclusion in an expert profile for tracheal intubation. Future studies should include a larger sample of practitioners, actual patients, and measures of the cognitive and affective components of expertise.

Building airtightness is a critical aspect for energy-efficient buildings as the energy performance of a building can be significantly reduced by poor airtightness. The Pulse technique has been regarded as a promising technology, measuring building airtightness at a low pressure of 4 Pa. However, due to the rapid dynamic nature of the test, a frequently raised question concerns the uniformity of the pressure distribution across the internal space of the test building during the air pulse release. In order to investigate this point, experimental work was conducted in a five-bedroom dwelling. All the tests were conducted at wind speeds less than 0.45 m/s to minimise the wind impact on the indoor pressure. The results show a pressure difference within the building during the Pulse test does exist, but considering the accuracy of differential pressure transducers, the deviation is not significant. In addition, a subtle variation is noted when the Pulse test was conducted at different locations on the ground floor, which may also be caused by variations in the environmental conditions. In terms of the airtightness measurement, a good overall agreement was found between the Pulse technique and the conventional blower door fan pressurisation method, which indirectly verified the uniformity of the indoor pressure distribution during both tests. Moreover, the error analysis demonstrated the validity of the measurement results for the two test methods in this study.

PathogenicWe recruited 13 adults (between 18 years and 45 years of age) withWhile most patients had daily seizures at seizure onset, seizure frequency declined or remitted during childhood and adulthood. The most common seizure type was tonic seizures (early) infancy, and tonic-clonic and focal impaired awareness seizures later in life. Ten individuals (77%) were seizure-free at last follow-up. In 38% of the individuals, earlier periods of seizure freedom lasting a minimum of 2 years followed by seizure recurrence had occurred. Of the 10 seizure-free patients, 4 were receiving a single antiseizure medication (ASM, carbamazepine, lamotrigine or levetiracetam), and 2 had stopped taking ASM. Intellectual disability (ID) ranged from mild to profound, with the majority (54%) of individuals in the severe category. At last contact, six individuals (46%) remained unable to walk independently, six (46%) had limb spasticity and four (31%) tetraparesis/tetraplegia. Six (46%) remained non-verbal, 10 (77%) had autistic features/autism, 4 (31%) exhibited aggressive behaviour and 4 (31%) destructive behaviour with self-injury. Four patients had visual problems, thought to be related to prematurity in one. Sleep problems were seen in six (46%) individuals.Seizure frequency declines over the years and most patients are seizure-free in adulthood. Longer seizure-free periods followed by seizure recurrence are common during childhood and adolescence. Most adult patients have severe ID. Motor, language and behavioural problems are an issue of continuous concern.

Pimobendan is a positive inotrope and balanced vasodilator via its actions as a calcium sensitiser and phosphodiesterase III inhibitor, respectively.1 There is strong evidence for its use in the treatment of dogs with congestive heart failure (CHF), with multiple clinical trials demonstrating a resultant increase in survival time.2-5 However, the use of pimobendan for treatment of heart disease in people has been associated with increased risk of arrhythmias.6 This effect is attributed to the racemic nature of pimobendan resulting in D and L chiral enantiomers, with the L-optical isomer having a significantly greater calcium sensitising effect.7-9 There is limited data available regarding any effect of treatment with pimobendan on the risk of arrhythmias in dogs. The aim of this article is to analyse the available data to determine whether evidenced-based conclusions can be drawn. In [dogs with cardiac disease] does treatment with [pimobendan] compared to [alternative treatments OR placebo] lead to [increased risk of arrhythmias]? The search strategy is available as a supplement to this article on Vet Record’s website at http://veterinaryrecord.bmj.com/content/183/22/693 ### Supplementary file 1 [vetreck5167-SP1.docx] Search last performed: 31 May, 2018 Paper 1: Effect of pimobendan on the incidence of arrhythmias in small breed dogs with myxomatous mitral valve degeneration (MMVD)10 Patient group: Eight client-owned small breed dogs (

Previous analysis of Phase 3 clinical trial data for colorectal cancer patients treated with cetuximab revealed that patients harboring a KRAS mutation did not benefit from treatment. This finding set the stage for one of the first examples of cancer personalized medicine. Confusingly, patients with a Glycine to Aspartic Acid mutation at amino acid 13 of KRAS (KRASG13D) appeared to respond positively to cetuximab, suggesting this mutation is an exception to the rule that KRAS mutations confer resistance to Epidermal Growth Factor Receptor (EGFR) inhibitors. Oncologists have stated that the mechanism that explains why the KRASG13D mutation is an exception should be identified before KRASG13D colorectal cancer patients should be treated differently. We have recently elucidated this mechanism using mathematical modeling of the KRAS biochemical system coupled with experimental biology. The mechanism we revealed involves a cetuximab-mediated reduction in HRAS and NRAS signaling within KRASG13D cancer cells, owing to impaired binding of KRASG13D to the tumor suppressor, Neurofibromin (NF1).

This paper introduces a comparison study of measuring the airtightness of a house-sized test chamber using the novel pulse technique and a low range blower door method in a sheltered environment. Eight different testing plates were prepared and applied to the improvised envelope of the chamber to establish different leakage characteristics. Each testing plate has a unique opening in its centre, achieved by obtaining different combinations of shape and thickness of the opening. By using the sheltered environment, the vagaries of the natural condition when testing within buildings have been reduced providing a more robust testing environment. This investigation focuses on how the air leakage rate calculated from the measurements made by both techniques compare with each other. Comparable results (0–5.3%) under most scenarios have been obtained. Larger discrepancies (14.6% and 21.8%) were observed in the two airtight scenarios due to insufficient pressure range achieved in a standard pulse test. This finding guided further improvement on the testing performance. Further pulse tests under different scenarios, involving the use of an internal barrier and various locations of the pulse unit were also performed to investigate the uniform pressure distribution and resilience to external interferences. It showed the internal barrier and location had minor impact (1.62%–4.65%) on the test results.

A pulse pressurisation technique is developed and utilised for determining building leakage at low pressure, based on a “quasi-steady pulse” concept. The underlying principle of the technique is to subject the building envelope to a known volume change in a short period of time (typically 1.5 s). The resulting pressure pulse is recorded, from which the leakage characteristic at low pressure is determined. The technique minimizes the effects of wind and buoyancy forces and has proven to be repeatable. It can use a compact and portable test rig and does not need to penetrate the building envelope. Therefore, it can obtain the leakage of a building very quickly and efficiently. Throughout the various stages of research and development of the pulse technique, experimental investigations have been carried out under different configurations and scenarios in order to validate the changes that have been made for the purpose of system development and optimisation. This paper provides an overview of experimental investigations in the validation process by covering comparison between blower door and pulse unit, comparison between piston-based pulse unit and nozzle-based pulse unit, testing with multiple pulse units in a large building, testing with a known opening, and testing in different building types with a range of volumes and airtightness levels. It enables us to understand the strengths and the limits of the pulse technique, from the experimental and practical perspectives. A good repeatability level (within ±5%) has been maintained throughout the various developmental stages and the average value of Q50/Q4 reported herein was in close agreement (

Motivated by intentions of avoiding large net fluid flow and enabling a more practical airtightness test for large buildings, a low-pressure Pulse pressurisation technique was developed for measuring building airtightness at pressures that are considered more representative of that experienced by buildings under natural conditions. Due to the short and dynamic operation, this technique is able to minimize wind and buoyancy effects during the measurement of building pressure. The investigation, based on the “quasi-steady” temporal inertia model, explores a technique that generates a pressure pulse inside a building by releasing a known amount of air pulse over 1.5 s using a compressed air tank. The volumetric flow rate of the air pulse released from the tank is obtained by measuring the transient pressure in the air tank during a test run. The air leakage through the building envelope is then obtained by accounting for the compressibility of indoor air. Simultaneously, the pressure variation within the envelope of test building is monitored. Therefore, the leakage-pressure relationship of the building envelope can be obtained. The validity of the theoretical model and the assumptions on which the model is based are validated using experimental and numerical investigations.

Quantitative analyses of calcareous nannofossils were performed on 50 ditch-cuttings samples from a well drilled in the northern Campos Basin, Brazil. Nine zones and two subzones were recognised in the Paleogene-Neogene section. The absence of zones NN9-NN7 (earliest late-latest middle Miocene), NP25-NP21 (Oligocene) and NP18-NP1 (earliest late Eocene-Paleocene) implies the occurrence of three stratigraphic breaks/unconformities within the studied interval. Nannofossil assemblages present suggest an open-ocean depositional environment under oligotrophic-surface water conditions for the Miocene section of the well. Hughesius spp. and Umbilicosphaera spp., here named the “small dark” group, were recognised as an index of high nutrient concentration. We suggest that small coccolith/nannolith size is a better indicator of eutrophic condition than taxonomic affinity. Morphometric analysis of specimens of Sphenolithus belemnos and Sphenolithus disbelemnos showed that size tends to decrease within the highstand system tract. The influx of nutrients associated with the highstand could explain this size reduction and may also support our hypothesis that small specimens are indicative of high nutrient concentrations in the surface water.

As an important indicator of construction quality and envelope integrity of buildings, airtightness is responsible for a considerable amount of energy losses associated with infiltration. It is crucial to understand building airtightness during construction and retrofitting to achieve a suitable envelope airtightness which is essential for obtaining a desirable building energy efficiency, durability and indoor environment. As a convenient means of measurement, the current steady pressurisation method has long been accepted as a standard testing method for measuring building airtightness. It offers an intuitive and robust approach for measuring building airtightness and performing building diagnostics. However, it also has some shortcomings that are mainly related to its high pressure measurement, requirement for skilful operation, long test duration and change to the building envelope. Efforts have been made by manufacturers and researchers to further improve its accuracy and practicality with much progress achieved. Work has also been done to develop alternative methods that can overcome some of the issues. This paper provides a practical review on the incumbent methodology and efforts that have been made over the past decades in research and development of other methods to achieve a similar purpose. It compares them in relation to aspects that are considered important in achieving an accurate, quick and practical measurement of building airtightness and the finding shows other methods such as acoustic and unsteady technique have their own advantages over the steady pressurisation method but also add some of their own restrictions, which therefore makes them suited for different applications., Highlights • This manuscript provides a review on the steady pressurisation. • The alternatives to the steady pressurisation method are reviewed and summarised. • Reviewed methods are compared with each other from perspectives that are considered important for a practical measurement. • Unsteady technique and acoustic method offer advantages but also add some of their own weakness.

The ability to visualize reporter gene expression in vivo has revolutionized all facets of biologic investigation and none more so than imaging applications in oncology. Near-infrared reporter gene imaging may facilitate more accurate evaluation of chemotherapeutic response in preclinical models of orthotopic and metastatic cancers. We report the development of a cell permeable, quenched squarine probe (CytoCy5S), which is reduced by Escherichia coli nitroreductase (NTR), resulting in a near-infrared fluorescent product. Time-domain molecular imaging of NTR/CytoCy5S reporter platform permitted noninvasive monitoring of disease progression in orthotopic xenografts of disseminated leukemia, lung, and metastatic breast cancer. This methodology facilitated therapeutic evaluation of NTR gene–directed enzymatic prodrug therapy with conventional metronidazole antibiotics. These studies show NTR/CytoCy5S as a near-infrared gene reporter system with broad preclinical and prospective clinical applications within imaging, and gene therapy, of cancer. Cancer Res; 73(4); 1276–86. ©2012 AACR.

This study presents a method to adapt existing hydronic systems in buildings to take advantage of low temperature district heating (LTDH). Plate radiators connected to double string heating circuits were considered in an optimization procedure, based on supply and return temperatures, to obtain the required logarithmic mean temperature difference (LMTD) for a low temperature heating system. The results of the analysis are presented as the average reduction of LMTD over the heating season compared to the base case design conditions. Two scenarios were investigated based on the assumption of a likely cost reduction in the end users' energy bills of 1% for each 1 °C reduction of return and average supply and return temperatures. The results showed possible discounts of 14% and 16% respectively, due to more efficient operation of the radiators. These were achieved without any intervention in the thermal envelope or to the heating systems, through simply adjusting the temperatures according to demand and properly controlling the plate radiators with thermostatic radiator valves (TRVs).

Windows are extremely useful multi-function devices which provide views, ventilation and passive solar gain, a means of escape, security and daylight gain. However, they can have a negative impact on a home's energy efficiency, particularly when the window area is large, and play a significant role in determining the heating and cooling load of a building. It has been estimated that around 47% of the heat lost from building envelop occurs through windows. This paper summarizes the impact of the Low Carbon Homes Program in terms of future requirements and areas of future research for windows' performance and investigates new window technologies that could help to meet these requirements. Copyright The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org, Oxford University Press.

Part 1 of this paper examines the uncertainties (errors) inherent in the determination of the low-pressure leakage of a building envelope. Current procedures use high-pressure data (typically 50 Pa) as a measure of the infiltration potential of an envelope. In reality, infiltration occurs at much lower pressures (typically 4 Pa). As a consequence, large uncertainties are inherent in the current procedures. It is shown that a technique for direct measurement of Q4 could reduce the uncertainty by a factor of three or more. One of the keys to such a measurement is to consecutively measure Dp with and without an imposed flow in a short time. In Part 2 of this paper, a technique is described that enables such measurements to be made.

Part 1 of this paper examined the uncertainties (errors) inherent in the determination of the low-pressure leakage of a building envelope. It was shown that a technique for direct measurement of Q4 could reduce the uncertainty by a factor of three or more. In Part 2, a technique is described that enables such measurements to be made. There are three key features that lead to a successful technique. The first is to measure Dp a short time before and after the pulse, thereby allowing wind effects to be largely eliminated. The second is to choose the shape and duration of the pulse, such that a period of quasi-steady flow is obtained. The third is to minimise the variation of Dp during the quasi-steady period, such that envelope flexing is not a problem. Examples of measurements are presented that demonstrate these key features. Further evidence of the suitability of the technique is provided by demonstrating its ability to determine a known change of opening. Comparisons are also made between the new technique, the conventional steady technique, and a theoretical model. It is concluded that the new technique allows the low-pressure leakage of a building to be determined to an accuracy that has not previously been possible.

Fidelity and robustness of neuronal action potential generation and conduction depends on the co-localization of voltage-gated sodium (NaV) and KCNQ2/3 potassium channel conductances at the axon in...

A new model for calculating the density of aqueous solutions of electrolytes has been developed. Parameters for 59 electrolytes were established on the basis of an extensive critical review of the published literature for solutions of one electrolyte in water, with over 10 700 points included. The average difference between the calculated and experimental density of solutions of water and one electrolyte is 0.10 kg m-3 with a standard deviation of 1.44 kg m-3. The model was validated by predicting the density of systems of two or more electrolytes in water. The average difference between experimental and calculated values for over 1600 points is 0.003 kg m-3 with a standard deviation of 1.39 kg m-3. The electrolytes studied are AlCl3, Al2(SO4)3, BaCl2, CaCl2, CdCl2, CdSO4, CoCl2, CoSO4, CrCl3, Cr2(SO4)3, CuCl2, CuSO4, FeCl2, FeSO4, FeCl3, Fe2(SO4)3, HCl, HCN, HNO3, H3PO4, H2SO4, KCl, K2CO3, KNO3, KOH, K2SO4, LiCl, Li2SO4, MgCl2, MgSO4, MnCl2, MnSO4, NaBr, NaCl, NaClO3, Na2CO3, NaF, NaHCO3, NaH2PO4, Na2HPO...

The spectral properties of a rigidified trimethine cyanine dye, Cy3B have been characterised. This probe has excellent fluorescent properties, good water solubility and can be bioconjugated. The emission properties of this fluorophore have also been investigated upon conjugation to an antibody. This study compared the conjugated emission properties of Cy3B with other commercially available fluorophores emitting at similar wavelengths.

A series of functionalized, water-soluble, pH-sensitive pentamethine cyanine (CyTM5) dyes has been designed and synthesized. These probes are fluorescent in acidic media but are non-fluorescent in an alkaline environment. Subtle changes to the structure of these probes can lead to pronounced changes in the pKa of these probes. These probes have been utilized in a cellular environment to detect localized changes in pH using the IN Cell Analyzer, a confocal imager formatted for imaging of cell-based assays.

To describe the use of glucagon infusion for adjunctive treatment of hypoglycemia in dogs.Multicenter retrospective case series.One university and 1 private veterinary referral hospital.Dogs were included if they were hospitalized and received glucagon therapy for hypoglycemia, defined as blood glucose concentration (BG)60 mg/dL. A total of 9 dogs were included from September 2005 to May 2014.None.The medical record for each eligible case was reviewed. Data recorded included signalment, presenting complaint, underlying disease process, presenting BG, BG after dextrose supplementation, BG before glucagon administration, maximum BG while receiving glucagon, and BG after discontinuation of glucagon, if available. Adverse reactions to glucagon and outcome of case were recorded if available. The most common causative disease was insulinoma (n = 7). Median serum glucose concentration on presentation was 30 mg/dL (20-41 mg/dL). The median bolus of glucagon was 50 ng/kg followed by a median maximum dose of a glucagon CRI of 15 ng/kg/min. The mean time period on glucagon CRI until normoglycemia (defined as BG60 mg/dL) was 7 hours. All hypoglycemic patients had improvement of BGs when glucagon was added. Statistically significant differences (P0.05) were found between BG measurements on glucagon CRI compared to BG at presentation, BG after dextrose, and BG prior to glucagon with a Friedman statistic of 17.3. A CRI was found to effectively increase the BG without recurrence of hypoglycemia after weaning. The majority of patients (5/9) survived to discharge.Glucagon CRI was accompanied by an increase in BG in hypoglycemic dogs. Glucagon CRI appears to be a safe method and can be readily utilized in most practice settings.

Cleidocranial dysplasia (CCD) is a generalized skeletal dysplasia with autosomal dominant inheritance. Recently, the CCD disease locus was localized to 23 [Mundlos et al., 1995] and 17 cM regions [Feldman et al., 1995], of chromosome band 6p21 by linkage studies of seven affected families. Of note, the 23 cM region contained a microdeletion detected in one family at D6S459, an interval that was excluded in the 17 cM overlapping region. Here, linkage of CCD to 6p21 was independently confirmed with a maximal two-point LOD score of Z=5.12 with marker D6S452 at θ=0.00. Recombinant events in two affected individuals defined a CCD region of 7 cM from D6S465 to D6S282, which overlapped with the CCD region containing the microdeletion but did not overlap with the 17 cM critical region from D6S282 to D6S291. These results suggest the refined localization of the CCD region to 6 cM spanning markers D6S438 to D6S282, thereby reviving the possibility that the CCD gene lies within the microdeletion at D6S459. © 1995 Wiley-Liss, Inc.

This study provides the first description of the range and immunogenicity of proteins excreted and/or secreted by living T. trichiura adult worms following their recovery from the human large intestine. Metabolic labelling of T. trichiura excretory/secretory (ES) products with [35S]-methionine revealed a range of proteins with prominent components at 52-54 kDa, 35-45 kDa & 17 kDa. In contrast, the major component of unlabelled T. trichiura ES, somatic whole worm and isolated stichosome extracts, and of [35S]-methionine labelled somatic extracts, was present at approximately 47 kDa. Similarly, the major 43 kDa protein present in unlabelled T. muris ES, somatic worm extract and [35S]-methionine labelled somatic worm extract, was only weakly detected in labelled T. muris ES. Pulse chase experiments demonstrated that after 20 h, the 43 kDa was a prominent component of T. muris ES. These data suggest that the 43/47 kDa protein of Trichuris adult worms is not a major constituent of newly synthesized ES but is either synthesized at a slower rate than other proteins, or sequestered or stored, most likely in the stichocytes, before release. Immunoprecipitations using a range of sera from T. trichiura-infected individuals demonstrated that many of the ES components are immunogenic. Antibody responses were vigorous in children with intense infections and negligible in parasitologically negative children. There was marked heterogeneity in responses to a 17 kDa antigen, with the age profile of anti-17 kDa antibody levels reflecting age-dependent infection intensities at the population level.