Identification of risk factors for ewe mortality during the pregnancy and lambing period in extensively managed flocks.

BACKGROUND: Ewe mortality during pregnancy and lambing is an issue for sheep producers globally, resulting in reduced productivity and profitability, compromised ewe welfare, and poor consumer perception. Despite these negative consequences, there was little investigation into factors associated with ewe death during this time. Therefore, this study aimed to assess associations between ewe body condition score (BCS), weight, reproductive parameters, and risk of mortality during pregnancy and lambing. METHODS: Four cohorts from three commercial New Zealand farms participated, with 13,142 ewe lambs enrolled and followed over time. Data were collected for five consecutive lambings. Visits aligned with key on-farm management times, specifically: prior to breeding, at pregnancy diagnosis (PD), prior to lambing (set-stocking), and, at weaning of their lambs. At each visit, ewes were weighed, BCS assessed and reproductive status was recorded when relevant (litter size at PD and lactation status after lambing). Ewes that died or were culled were recorded, and any ewes that were absent from consecutive visits were presumed dead. Logistic regressions were developed to assess the relationship between weight and BCS at each visit, PD result (single or multiple-bearing) and lactation status (wet or dry) in each year, and, risk of mortality during the pregnancy and lambing period in each year. RESULTS: In the PD to weaning period, mortality incidence ranged from 6.3 to 6.9% for two-tooth (18-months-old at breeding) to mixed-age (54-months-old at breeding) ewes. For ewe lambs (7 to 8-months-old at breeding), mortality was 7.3% from set-stocking to weaning. Heavier ewe lambs at PD were less likely to die during lambing (OR: 0.978, p = 0.013), as were those with greater set-stocking BCS. In subsequent years, BCS was a predictor of ewe death, with odds of mortality greatest for ewes < BCS 2.5. Additionally, for poorer BCS ewes, increasing weight reduced risk of mortality, but there was no impact of increasing weight in greater BCS ewes. CONCLUSIONS: This study identified risk factors associated with ewe mortality during the pregnancy and lambing period. Flock owners can use these to either cull at-risk ewes or proactively intervene to reduce likelihood of mortality, thereby improving flock productivity, profitability and welfare.

Assessing and visualising hazard impacts to enhance the resilience of Critical Infrastructures to urban flooding.

The design, construction and maintenance of Critical Infrastructures (CI) is commonly based on standards that are rigorous, so as to withstand any climate or weather-linked pressures. However, due to climate change, climate characteristics may shift, resulting in increased frequency/magnitude of potential failures, or exposure to new unknown risks. As vital components for the normal functioning of modern societies, the resilience of CIs under climate stressors encompasses their structural integrity, their operational elements, and their capacity to maximize business output. In this work, we propose an integrated and participatory methodological approach to enhance the resilience of interconnected CIs to urban flooding under climate change, by assessing the risk and introducing adaptation measures. The main objectives of the proposed methodology and approach are: (i) to provide scientific evidence for better understanding of how future climate regimes might affect normal operation of interconnected CI in urban areas during their lifespan; (ii) to assess the cost-effectiveness of different adaptation measures; (iii) to involve local stakeholders and operators in the co-design of the approach, as well as the assessment and the evaluation of adaptation measures; (iv) to combine computational modelling with advanced 3D visualisation techniques for effectively engaging stakeholders in decision making; (v) to include risk assessment and damage functions co-designed by end-users and local stakeholders; (vi) to integrate all of the aforementioned components in a specifically designed cloud platform as a Decision Support System for end-users, (vii) to validate the DSS by the end users and local stakeholders. The paper presents the computational background and tools. Additionally, it describes a Case Study in Torbay, UK, where the full methodology and the proposed participatory approach have been applied, with all the specifics, i.e., the scenarios of extreme flooding, the numerical and visualisation results, the response of the stakeholders and the evaluation of selected adaptation measures.

Preliminary results of using inertial sensors to detect dementia- related wandering patterns.

We present a solution for detecting dementia-related travel patterns using only inertial sensors. The results and lessons learnt from the experiments on dementia and non-dementia subjects are reported.

Calibration of a 1D/1D urban flood model using 1D/2D model results in the absence of field data.

Recently increased flood events have been prompting researchers to improve existing coupled flood-models such as one-dimensional (1D)/1D and 1D/two-dimensional (2D) models. While 1D/1D models simulate sewer and surface networks using a one-dimensional approach, 1D/2D models represent the surface network by a two-dimensional surface grid. However their application raises two issues to urban flood modellers: (1) stormwater systems planning/emergency or risk analysis demands for fast models, and the 1D/2D computational time is prohibitive, (2) and the recognized lack of field data (e.g. Hunter et al. (2008)) causes difficulties for the calibration/validation of 1D/1D models. In this paper we propose to overcome these issues by calibrating a 1D/1D model with the results of a 1D/2D model. The flood-inundation results show that: (1) 1D/2D results can be used to calibrate faster 1D/1D models, (2) the 1D/1D model is able to map the 1D/2D flood maximum extent well, and the flooding limits satisfactorily in each time-step, (3) the 1D/1D model major differences are the instantaneous flow propagation and overestimation of the flood-depths within surface-ponds, (4) the agreement in the volume surcharged by both models is a necessary condition for the 1D surface-network validation and (5) the agreement of the manholes discharge shapes measures the fitness of the calibrated 1D surface-network.

An analysis of the combined consequences of pluvial and fluvial flooding.

Intense rainfall in urban areas often generates both pluvial flooding due to the limited capacity of drainage systems, as well as fluvial flooding caused by deluges from river channels. The concurrence of pluvial and fluvial flooding can aggravate their (individual) potential damages. To analyse the impact caused by individual and composite type of flooding, the SIPSON/UIM model, an integrated 1D sewer and 2D overland flow was applied to numerical modelling. An event matrix of possible pluvial scenarios was combined with hypothetic overtopping and breaching situations to estimate the surface flooding consequences in the Stockbridge area, Keighley (Bradford, UK). The modelling results identified different flooding drivers in different parts of the study area and showed that the worst scenarios resulted from synthesised events.

Glyceraldehyde is present in rat lens and its level is increased in diabetes mellitus.

PURPOSE: OP-lysine, a glycation product of lysine residues of proteins, has been reported to be formed with glyceraldehyde and glycolaldehyde as precursors in the lens, and has been suggested to play a role in senile cataracts. However, there has been no reliable information regarding the content of glyceraldehyde in tissues. This study determined the glyceraldehyde levels in the lenses of normal and diabetic rats. METHODS: Glyceraldehyde was derivatized to a fluorescent compound, and the compound was then quantified by high-performance liquid chromatography. RESULTS: The lens glyceraldehyde levels in normal and diabetic rats were 0.75 +/- 0.06 and 1.26 +/- 0.21 nmol/g wet weight (means +/- standard deviations of 6 animals, p < 0.01), respectively. Isolated rat lenses accumulated a higher level of glyceraldehyde when cultured for 6 days in 25.5 mM glucose than when cultured in 5.5 mM glucose. CONCLUSIONS: Glyceraldehyde was found to be present in the lens and was increased in diabetes mellitus. OP-lysine is thus likely to be a potential risk factor for senile and diabetic cataracts.

An integrated inundation model for highly developed urban areas.

A numerical model is developed in this study with various components for simulating the complex flow phenomena in urban drainage basins. The model integrates the HEC-1 model, a 1-D dynamic channel-flow model, a 2-D non-inertia overland-flow model and the SWMM model to reflect the hydraulic processes in areas with different characteristics. The inundation of underground infrastructure during flood is also considered in the model. The typhoon Nari event in 2001, which resulted in severe flood in downtown Taipei, is simulated by the model. The result is compared with the survey records of flooded areas, which reveals the storage effect of underground infrastrucures is significant to the simulation results of highly developed urban areas.

Pyridoxal-aminoguanidine adduct is more effective than aminoguanidine in preventing neuropathy and cataract in diabetic rats.

We examined the ability of a pyridoxal-aminoguanidine adduct with both antiglycation and antioxidant activities in vitro to protect against neuropathy and cataract in streptozotocin-diabetic rats and compared the result with that of aminoguanidine. In vivo antiglycation and antioxidant activities were also compared between the adduct and aminoguanidine. Diabetic rats were given either of the compounds in their drinking water (9 mM) for 7 weeks. Neither compound affected body weight, blood glucose level or urine volume. The adduct, but not aminoguanidine, significantly improved motor nerve conduction velocity. The time to develop cataract was longer in adduct-treated rats than in untreated and aminoguanidine-treated rats. The increase in opacification of lenses in culture medium containing high glucose levels (55.5 mM) was more efficiently attenuated by the adduct than by aminoguanidine. Adduct and aminoguanidine similarly lowered glycated hemoglobin levels. The level of urinary 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage, and the level of liver malondialdehyde plus 4-hydroxy-2-alkenals, a marker of tissue lipid peroxidation, both of which were elevated by diabetes, were significantly reduced by the adduct but not by aminoguanidine. These findings indicate that the pyridoxal-aminoguanidine adduct is superior to aminoguanidine in preventing diabetic neuropathy and cataracts, and we suggest that this may be at least partly due to the higher antioxidant activity of the former.

Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein.

Ghrelin, a stomach-derived orexigenic hormone, has stimulated great interest as a potential target for obesity control. Pharmacological evidence indicates that ghrelin's effects on food intake are mediated by neuropeptide Y (NPY) and agouti-related protein (AgRP) in the central nervous system. These include intracerebroventricular application of antibodies to neutralize NPY and AgRP, and the application of an NPY Y1 receptor antagonist, which blocks some of the orexigenic effects of ghrelin. Here we describe treatment of Agrp(-/-);Npy(-/-) and Mc3r(-/-);Mc4r(-/-) double knockout mice as well as Npy(-/-) and Agrp(-/-) single knockout mice with either ghrelin or an orally active nonpeptide ghrelin agonist. The data demonstrate that NPY and AgRP are required for the orexigenic effects of ghrelin, as well as the involvement of the melanocortin pathway in ghrelin signaling. Our results outline a functional interaction between the NPY and AgRP pathways. Although deletion of either NPY or AgRP caused only a modest or nondetectable effect, ablation of both ligands completely abolished the orexigenic action of ghrelin. Our results establish an in vivo orexigenic function for NPY and AgRP, mediating the effect of ghrelin.

Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients.

X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency characterized by extreme susceptibility to Epstein-Barr virus. The XLP disease gene product SH2D1A (SAP) interacts via its SH2 domain with a motif (TIYXXV) present in the cytoplasmic tail of the cell-surface receptors CD150/SLAM, CD84, CD229/Ly-9, and CD244/2B4. Characteristically, the SH2D1A three-pronged interaction with Tyr(281) of CD150 can occur in absence of phosphorylation. Here we analyze the effect of SH2D1A protein missense mutations identified in 10 XLP families. Two sets of mutants were found: (i) mutants with a marked decreased protein half-life (e.g. Y7C, S28R, Q99P, P101L, V102G, and X129R) and (ii) mutants with structural changes that differently affect the interaction with the four receptors. In the second group, mutations that disrupt the interaction between the SH2D1A hydrophobic cleft and Val +3 of its binding motif (e.g. T68I) and mutations that interfere with the SH2D1A phosphotyrosine-binding pocket (e.g. C42W) abrogated SH2D1A binding to all four receptors. Surprisingly, a mutation in SH2D1A able to interfere with Thr -2 of the CD150 binding motif (mutant T53I) severely impaired non-phosphotyrosine interactions while preserving unaffected the binding of SH2D1A to phosphorylated CD150. Mutant T53I, however, did not bind to CD229 and CD224, suggesting that SH2D1A controls several critical signaling pathways in T and natural killer cells. Because no correlation is present between identified types of mutations and XLP patient clinical presentation, additional unidentified genetic or environmental factors must play a strong role in XLP disease manifestations.

Complex of polyelectrolyte network with surfactant as novel shape memory networks.

Poly(acrylic acid-co-methyl methacrylate)-cetyltrimethylammonium bromide (P(AA-co-MMA)-C16TAB) complex has shape memory behavior due to the formation of crystalline aggregates among the long alkyl chains of C16TAB in the complex, and can be regarded as a novel shape memory network.

Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass.

Genetic and pharmacological studies have defined a role for the melanocortin-4 receptor (Mc4r) in the regulation of energy homeostasis. The physiological function of Mc3r, a melanocortin receptor expressed at high levels in the hypothalamus, has remained unknown. We evaluated the potential role of Mc3r in energy homeostasis by studying Mc3r-deficient (Mc3r(-/-)) mice and compared the functions of Mc3r and Mc4r in mice deficient for both genes. The 4-6-month Mc3r-/- mice have increased fat mass, reduced lean mass and higher feed efficiency than wild-type littermates, despite being hypophagic and maintaining normal metabolic rates. (Feed efficiency is the ratio of weight gain to food intake.) Consistent with increased fat mass, Mc3r(-/-) mice are hyperleptinaemic and male Mc3r(-/-) mice develop mild hyperinsulinaemia. Mc3r(-/-) mice did not have significantly altered corticosterone or total thyroxine (T4) levels. Mice lacking both Mc3r and Mc4r become significantly heavier than Mc4r(-/-) mice. We conclude that Mc3r and Mc4r serve non-redundant roles in the regulation of energy homeostasis.

Role of the melanocortin-4 receptor in metabolic rate and food intake in mice.

We evaluated the role of the melanocortin-4 receptor (MC-4R) in the control of metabolic rate and food intake in mice. Intraperitoneal administration of the non-selective MC-R agonist melanotan II (MT-II; a cyclic heptapeptide) increases metabolic rate in wildtype mice, while MC-4R knockout mice are insensitive to the effects of MT-II on metabolic rate. MC-4R knockout mice are also insensitive to the effects of MT-II on reducing food intake. We conclude that MC-4R can mediate control of both metabolic rate and food intake in mice. We infer that a role for MC-3R in mediating the acute effects of MT-II on basal metabolic rate and food intake in wildtype mice seems limited.

A new power law for determination of total (125)I seed activity for ultrasound-guided prostate implants: clinical evaluations.

PURPOSE: The intraoperative planning with peripheral loading approach is an important technique for ultrasound-guided transperineal prostate implant. In this paper a sphero-cylindrical dose model is described to generate a new power law or a look-up table for determination of the total (125)I activity required to deliver a prescription dose to a given prostate volume. METHODS AND MATERIALS: Dose calculations were based on the new standards for (125)I seeds (model 6711) implemented by the National Institute of Standards and Technology (NIST) in 1999. Using the sphero-cylindrical dose model with peripheral loading approach, a new power law for calculating total activity of radioactive iodine required to deliver a prescribed dose for the target volume was developed. Accounting for random variation of the seed positioning in the prostate and the current air-kerma strength standard of (125)I seeds, this new power law is formulated as follows: A (mCi) = 2.15 d (cm)(2.00) where A is apparent activity in mCi, or A (U) = 1. 69 d (cm)(2.00) where A is air-kerma strength in U, required to deliver a cumulative dose of 145 Gy to a prostate gland with an average dimension, d, in centimeters. RESULTS: The efficacy of using the new power law in prostate implants was demonstrated. For clinical evaluations of this new power law, 40 patients were chosen in 1998. The average D(90) of these 40 patients was 172.0 Gy (SD +/- 29 Gy). This means that on the average, 90% of the target volume received was 172.0 Gy. The average coverage index (CI) in this study was 94.7 (SD +/- 4.7). As a result, 94.7% of the target volume received the prescription dose. The dose homogeneity index (HI) which measured the degree of the dose inhomogeneity was 0.38 (SD +/- 0.21). CONCLUSION: This new and simple power law or a new mCi-volume look-up table for (125)I seed prostate implantation has been developed and formulated for clinical use. Clinical evaluations expressed in quantitative parameters such as D(90), CI, and HI in prostate implants have been thoroughly analyzed and clearly demonstrated the efficacy of this approach.

Point dose variations with time during traditional brachytherapy for cervical carcinoma.

In traditional brachytherapy for carcinoma of the cervix, doses are often prescribed to specifically chosen points (A and B) and the normal tissue tolerance calculated at specific reference points in the bladder and rectum. These tolerance doses are often used to modify the brachytherapy treatment plan. It is inherently assumed that the position of the brachytherapy applicator does not change in relation to the relevant anatomical structures over the time-course of an implant. To assess the accuracy of this assumption, 2 sets of localization films were obtained for each implant in 28 patients, 1 prior to loading and another after the removal of the radioactive sources. Significant applicator movement and, consequently, significant dose variations were ob: served. Therefore, isolated one-time dose measurements to normal critical structures should not be used as the sole basis for making therapeutic decisions. The magnitude of dose variations and their clinical significant are discussed.

Clinical heterogeneity in autosomal dominant optic atrophy in two 3q28-qter linked central Illinois families.

PURPOSE: To examine the clinical and genetic heterogeneity of autosomal dominant optic atrophy among two unrelated central Illinois families. METHODS: Forty-three individuals from two pedigrees had complete eye examinations. Linkage analysis was performed with microsatellite markers from the region 3q28-29. RESULTS: Visual acuity in 21 affected individuals ranged from 20/25 to 20/800. Vision loss was more severe in males than females (P = 0.02). Color vision testing revealed generalized dyschromatopsia. Both visual acuity and color vision deteriorated with age. Linkage was established to chromosome 3q28-29 (LODmax = 4.68 for D3S2305). CONCLUSION: Autosomal dominant optic atrophy linked to chromosome 3q28-29 shows intrafamilial phenotypic variation as well as sex-influenced severity in two Midwestern families.

VEGF gene delivery to muscle: potential role for vasculogenesis in adults.

Constitutive expression of VEGF after implantation of genetically engineered myoblasts into non-ischemic muscle led to an increase in vascular structures. Previously, effects of VEGF delivery to adult muscle have only been reported in ischemic tissues. The resulting vascular structures were reminiscent of those formed during embryonic vasculogenesis, rather than angiogenesis, sprouting from preexisting vessels. Initially, VEGF caused an accumulation of endothelial cells and macrophages, followed by networks of vascular channels and hemangiomas with locally high serum VEGF levels. No effects were evident in adjacent tissue or contralateral legs, where low serum VEGF was detected. These data suggest that the induction by VEGF of angiogenesis or vasculogenesis may be dose-dependent. Furthermore, VEGF expression must be carefully modulated, as overexpression is deleterious.

Pudendal nerve latency. Does it predict outcome of anal sphincter repair?

PURPOSE: Electrophysiologic evaluation has been suggested as a means of identifying prognostic factors for patients with fecal incontinence who undergo anal sphincter repair. The purpose of this study was to evaluate the results of anal sphincter repair in patients with documented pudendal neuropathy and to determine the usefulness of electrophysiologic studies for prognostication of sphincteroplasty. METHODS: A retrospective review of a series of patients undergoing electrophysiologic studies and anterior anal sphincteroplasty was performed. Data collected included age, standardized incontinence scores (preoperative, immediately postoperative, and current follow-up), and results of pudendal nerve terminal motor latency and monopolar electromyography. Outcomes of sphincteroplasty were designated as excellent, good, fair, or poor based on incontinence scores. Prolonged pudendal nerve terminal motor latency was defined as longer than 2.2 ms and elevated as unilateral or bilateral. RESULTS: During the time period of the study (1991-1996), 15 patients had electrophysiologic studies and underwent sphincteroplasty. Twelve patients (80 percent) were available for follow-up and form the basis for this study. All patients were women, with a mean age of 45 +/- 18.6 (27-75) years and a mean follow-up of 49.7 +/- 18.6 (20.4-72.6) months. Mean duration of incontinence preoperatively was 13 +/- 16.1 (range, 1-58) years. The incontinence score was 15.8 +/- 3.5 preoperatively, 5.4 +/- 4.5 postoperatively, and 5 +/- 5.1 currently for all 12 patients. There was one patient with normal pudendal nerve terminal motor latency. In the four patients with bilateral prolonged pudendal nerve terminal motor latency, the incontinence scores were 15 +/- 4.2 preoperatively, 8.5 +/- 5.3 postoperatively, and 6 +/- 6.1 (statistically significant compared with preoperation) currently. Seven patients were found to have unilateral prolonged pudendal nerve terminal motor latency with incontinence scores of 16.3 +/- 3.5 preoperatively, 4.4 +/- 3.2 (statistically significant compared with preoperation) postoperatively, and 5.1 +/- 4.9 (statistically significant compared with preoperation) currently. Based on incontinence scores, results of the sphincteroplasty at the most current follow-up were as follows: no neuropathy, excellent in one patient; unilateral neuropathy, five with good/excellent results, two with fair/poor results; bilateral neuropathy, two with good/excellent results, two with fair/poor results (P > 0.05 bilateral vs. unilateral). By monopolar electromyographic examination, external and sphincter denervation was noted in 11 patients; their incontinence scores were 15.5 +/- 3.5 preoperatively, 5.9 +/- 4.3 (statistically significant compared with preoperation) postoperatively, and 5.5 +/- 5.0 (statistically significant compared with preoperation) currently. Monopolar electromyographic results in the puborectalis included four normal examinations and six that were unobtainable. In the two patients with puborectalis denervation, the incontinence scores were 19.5 +/- 0.7 preoperatively, 8.5 +/- 4.9 postoperatively, and 2.5 +/- 3.5 (statistically significant compared with preoperation) currently. CONCLUSIONS: Anterior anal sphincteroplasty in patients with unilateral or bilateral prolonged pudendal nerve terminal motor latency can provide significant improvement in continence with minimum morbidity. Therefore, correction of the anatomic sphincter defect should still be considered, even in patients with documented pudendal neuropathy.

Evaluation of dose calculation algorithm of the peacock system for multileaf intensity modulation collimator.

PURPOSE: To evaluate the dose calculation algorithm used in the inverse treatment planning computer system for the intensity modulation multileaf collimator. METHODS AND MATERIALS: The inverse treatment-planning computer system calculates the intensities of multiple pencil beams to achieve an optimal distribution and modulates the beam intensity through the special multileaf collimator. The system's dose calculation algorithm made the two basic assumptions: (a) The tissue-maximum ratios (TMRs) of a single pencil beam have the same values as TMRs for raylines through each pencil beam that are determined from percentage depth dose isodose curves along the long axis of the 2 x 20 cm2 field with all leaves open; and (b) the relative output factors (ROF) of each pencil beam also have the same values as the rayline TMR at d(max) of the 2 x 20 cm2 field. To verify these two assumptions, a special multileaf collimator was installed to our linear accelerator which produces 4 MV x-rays. The TMRs and ROFs for the single leaves 1 through 10 were measured using an ion chamber and TLD dosimeter in either a water or a polystyrene phantom. The values of rayline TMRs were calculated from the measured crossplane isodose curves of the 2 x 20 cm2 field. Comparisons were made between these two sets of data. RESULTS: Based on our measurements, we found that the ROFs of a pencil beam obtained from the rayline TMRs at d(max) are as much as 7.6% greater than that of single pencil beams. The ROF of the 1 x 1 cm2 pencil beam is 4 and 6.5% less than that of a cluster of four neighboring pencil beams forming a 2 x 2 cm2, and a 2 x 20 cm2 field respectively. However, the rayline TMRs are generally larger than the TMRs of a single pencil beam. At a depth of 8 cm, the average depth in the middle of intracranial space, the rayline TMRs of the pencil beams of leaves 1 and 10 are 5.4 and 9% higher than a single pencil beam TMR at the same depth, respectively. Also interesting is to note that the TMRs of each of the single pencil beams were found to be equal. CONCLUSIONS: In our article, evaluations and comparisons of TMRs and ROFs were made for two extreme conditions. The measured values of TMRs and ROFs of a single beam have been shown to be significantly different from those used in the calculations. Because both the TMR and ROF are influenced by the scattering radiation in the same direction, the deviations for these two factors would be expected to be magnified. Thus, for the two extreme situations we have investigated, dose deviations would be on the order of 15%. In real patient treatment; of course, these deviations may be somewhat less, but still significant. Our results, however, show that further investigations are warranted.