AM1- receptor dependent protection by intermedin of human vascular and cardiac non-vascular cells from ischaemia-reperfusion injury

Intermedin (IMD) protects rodent heart and vasculature from oxidative stress and ischaemia. Less is known about distribution of IMD and its receptors and the potential for similar protection in man. Expression of IMD and receptor components were studied in human aortic endothelium cells (HAECs), smooth muscle cells (HASMCs), cardiac microvascular endothelium cells (HMVECs) and fibroblasts (v-HCFs). Receptor subtype involvement in protection by IMD against injury by hydrogen peroxide (H2O2, 1 mmol l?¹) and simulated ischaemia and reperfusion were investigated using receptor component-specific siRNAs. IMD and CRLR, RAMP1, RAMP2 and RAMP3 were expressed in all cell types.When cells were treated with 1 nmol l?¹ IMD during exposure to 1 mmol l?¹ H2O2 for 4 h, viability was greater vs. H2O2 alone (P<0.05 for all cell types). Viabilities under 6 h simulated ischaemia differed (P<0.05) in the absence and presence of 1 nmol l?¹ IMD: HAECs 63% and 85%; HMVECs 51% and 68%; v-HCFs 42% and 96%. IMD 1 nmol l?¹ present throughout ischaemia (3 h) and reperfusion (1 h) attenuated injury (P<0.05): viabilities were 95%, 74% and 82% for HAECs, HMVECs and v-HCFs, respectively, relative to those in the absence of IMD (62%, 35%, 32%, respectively). When IMD 1 nmol l?¹ was present during reperfusion only, protection was still evident (P<0.05, 79%, 55%, 48%, respectively). Cytoskeletal disruption and protein carbonyl formation followed similar patterns. Pre-treatment (4 days) of HAECs with CRLR or RAMP2, but not RAMP1 or RAMP3, siRNAs abolished protection by IMD (1 nmol l?¹) against ischaemia-reperfusion injury. IMD protects human vascular and cardiac non-vascular cells from oxidative stress and ischaemia-reperfusion,predominantly via AM1 receptors.

Using vulnerability performance indicators to attain food supply chain robustness

High effectiveness and leanness of modern supply chains (SCs) increase their vulnerability, i.e. susceptibility to disturbances reflected in non-robust SC performances. Both the SC management literature and SC professionals indicate the need for the development of SC vulnerability assessment tools. In this article, a new method for vulnerability assessment, the VULA method, is presented. The VULA method helps to identify how much a company would underperform on a specific Key Performance Indicator in the case of a disturbance, how often this would happen and how long it would last. It ultimately informs the decision about whether process redesign is appropriate and what kind of redesign strategies should be used in order to increase the SC's robustness. The applicability of the VULA method is demonstrated in the context of a meat SC using discrete-event simulation to conduct the performance analysis.

Are there developmentally distinct motor indicators of pain in preterm infants?

The aims of this study were to examine preterm infant reactions to pain in detail over prolonged time periods using multiple measures, and to assess the value of including specific body movements of the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP) system to evaluate pain. Ten preterm infants born at 31 weeks mean gestational age (GA) and mean birth weight 1676 g were studied during a routine blood collection in a Level III neonatal intensive care unit (NICU). At 32-week post-conceptional age, computerized physiologic and video recordings were obtained continuously for 60 min (prior to, during and after lance). Motor and facial behaviors were coded independently, using the NIDCAP and the NFCS (Neonatal Facial Coding System), respectively, and compared with heart rate (HR) and oxygen saturation responses. Of the movements hypothesized to be stress cues in the NIDCAP model, extension of arms and legs (80%) and finger splay (70%) were the most common following lance. Contrary to the model, most infants (70%) had lower incidence of twitches and startles post-lance compared to baseline. Whereas all infants showed some NFCS response to lance, for three infants, the magnitude was low. HR increased and oxygen saturation decreased post-lance. Infants with more prior pain exposure, lower Apgar, and lower GA at birth, displayed more motor stress cues but less facial activity post-lance. Extension of extremities and finger splay, but not twitches and startles, from the NIDCAP, appear to be stress cues and show promise as clinical pain indicators to supplement facial and physiological pain measures in preterm infants.

Validation of non‑stationary precipitation series for site‑specific impact assessment: comparison of two statistical downscaling techniques

Statistical downscaling (SD) methods have become a popular, low-cost and accessible means of bridging the gap between the coarse spatial resolution at which climate models output climate scenarios and the finer spatial scale at which impact modellers require these scenarios, with various different SD techniques used for a wide range of applications across the world. This paper compares the Generator for Point Climate Change (GPCC) model and the Statistical DownScaling Model (SDSM)—two contrasting SD methods—in terms of their ability to generate precipitation series under non-stationary conditions across ten contrasting global climates. The mean, maximum and a selection of distribution statistics as well as the cumulative frequencies of dry and wet spells for four different temporal resolutions were compared between the models and the observed series for a validation period. Results indicate that both methods can generate daily precipitation series that generally closely mirror observed series for a wide range of non-stationary climates. However, GPCC tends to overestimate higher precipitation amounts, whilst SDSM tends to underestimate these. This infers that GPCC is more likely to overestimate the effects of precipitation on a given impact sector, whilst SDSM is likely to underestimate the effects. GPCC performs better than SDSM in reproducing wet and dry day frequency, which is a key advantage for many impact sectors. Overall, the mixed performance of the two methods illustrates the importance of users performing a thorough validation in order to determine the influence of simulated precipitation on their chosen impact sector.

Laterality as an indicator of emotional stress in ewes and lambs during a separation test

We assessed motor laterality in sheep to explore species-specific brain hemi-field dominance and how this could be affected by genetic or developmental factors. Further, we investigated whether directionality and strength of laterality could be linked to emotional stress in ewes and their lambs during partial separation. Forty-three ewes and their singleton lambs were scored on the (left/right) direction of turn in a y-maze to rejoin a conspecific (laterality test). Further, their behavioural response (i.e. time spent near the fence, vocalisations, and activity level) during forced separation by an open-mesh fence was assessed (separation test). Individual laterality was recorded for 44.2 % ewes (significant right bias) and 81.4 % lambs (equally biased to the left and the right). There was no significant association in side bias between dams and offspring. The Chi-squared test revealed a significant population bias for both groups (p < 0.05). Evolutionary adaptive strategies or stimuli-related visual laterality may provide explanation for this decision-making process. Absolute strength of laterality (irrespective of side) was high (Kolmogorov–Smirnov test, dams: D = 0.2; p < 0.001; lambs: D = 0.36, p < 0.0001). The Wilcoxon test showed that lateralised lambs and dams spent significantly more time near each other during separation than non-lateralised animals (p < 0.05), and that lateralised dams were also more active than non-lateralised ones. Arguably, the lateralised animals showed a greater attraction to their pair because they were more disturbed and thus required greater reassurance. The data show that measures of laterality offer a potential novel non-invasive indicator of separation stress.

Crack propagation in non-homogenous materials: Evaluation of mixed-mode SIFs, T-stress and kinking angle using a variant EFG method

A new variant of the Element-Free Galerkin (EFG) method, that combines the diffraction method, to characterize the crack tip solution, and the Heaviside enrichment function for representing discontinuity due to a crack, has been used to model crack propagation through non-homogenous materials. In the case of interface crack propagation, the kink angle is predicted by applying the maximum tangential principal stress (MTPS) criterion in conjunction with consideration of the energy release rate (ERR). The MTPS criterion is applied to the crack tip stress field described by both the stress intensity factor (SIF) and the T-stress, which are extracted using the interaction integral method. The proposed EFG method has been developed and applied for 2D case studies involving a crack in an orthotropic material, crack along an interface and a crack terminating at a bi-material interface, under mechanical or thermal loading; this is done to demonstrate the advantages and efficiency of the proposed methodology. The computed SIFs, T-stress and the predicted interface crack kink angles are compared with existing results in the literature and are found to be in good agreement. An example of crack growth through a particle-reinforced composite materials, which may involve crack meandering around the particle, is reported.