Glycaemic control in the perioperative period

The prevalence of type 2 diabetes mellitus and the potential for perioperative dysglycaemia (hyperglycaemia, hypoglycaemia, stress-induced hyperglycaemia, or glucose variability) continue to increase dramatically. The majority of investigations on perioperative glycaemic control focused on critically ill patients and concentrated on goals of therapy, level of intensity of insulin infusion, feeding regimes, concerns over hypoglycaemia, and promulgation of recent guidelines calling for less strict glucose control. Areas of perioperative glycaemic control that deserve further investigation include preoperative identification of patients with undiagnosed type 2 diabetes and other forms of dysglycaemia, determination of appropriate intraoperative glucose goals, and establishment of the impact and natural history of perioperative abnormalities in glucose homeostasis. In the heterogeneous adult perioperative population, it is unlikely that one standard of perioperative glycaemic control is appropriate for all patients. This review presents recent evidence and expert guidance to aid preoperative assessment, intraoperative management, and postoperative care of the dysglycaemic adult patien

The influence of long- and short-term volcanic strain on aquifer pressure:a case study from Soufrière Hills Volcano, Montserrat (W.I.)

Aquifers are poroelastic bodies that respond to strain by changes in pore pressure. Crustal deformation due to volcanic processes induces pore pressure variations that are mirrored in well water levels. Here, we investigate water level changes in the Belham valley on Montserrat over the course of two years (2004-2006). Using finite element analysis, we simulate crustal deformation due to different volcanic strain sources and the dynamic poroelastic aquifer response. While some additional hydrological drivers cannot be excluded, we suggest that a poroelastic strain response of the aquifer system in the Belham valley is a possible explanation for the observed water level changes. According to our simulations, the shallow Belham aquifer responds to a steadily increasing sediment load due to repeated lahar sedimentation in the valley with rising aquifer pressures. A wholesale dome collapse in May 2006 on the other hand induced dilatational strain and thereby a short-term water level drop in a deeper-seated aquifer, which caused groundwater leakage from the Belham aquifer and thereby induced a delayed water level fall in the wells. The system thus responded to both gradual and rapid transient strain associated with the eruption of Soufrière Hills Volcano (Montserrat). This case study gives field evidence for theoretical predictions on volcanic drivers behind hydrological transients, demonstrating the potential of hydrological data for volcano monitoring. Interrogation of such data can provide valuable constraints on stress evolution in volcanic systems and therefore complement other monitoring systems. The presented models and inferred results are conceptually applicable to volcanic areas worldwide

Nuclear Dbf2-related protein kinases (NDRs) in isolated cardiac myocytes and the myocardium: activation by cellular stresses and by phosphoprotein serine-/threonine-phosphatase inhibitors

The nuclear Dbf2-related protein kinases 1 and 2 (NDR1/2) are closely-related AGC family kinases that are strongly conserved through evolution. In mammals, they are activated inter alia by phosphorylation of an hydrophobic domain threonine-residue [NDR1(Thr-444)/NDR2(Thr-442)] by an extrinsic protein kinase followed by autophosphorylation of a catalytic domain serine-residue [NDR1(Ser-281)/NDR2(Ser-282)]. We examined NDR1/2 expression and regulation in primary cultures of neonatal rat cardiac myocytes and in perfused adult rat hearts. In myocytes, transcripts for NDR2, but not NDR1, were induced by the hypertrophic agonist, endothelin-1. NDR1(Thr-444) and NDR2(Thr-442) were rapidly phosphorylated (maximal in 15-30 min) in myocytes exposed to some phosphoprotein Ser-/Thr-phosphatase 1/2 inhibitors (calyculin A, okadaic acid) and, to a lesser extent, by hyperosmotic shock, low concentrations of H(2)O(2), or chelerythrine. In myocytes adenovirally-transduced to express FLAG-NDR2 (which exhibited a mainly-cytoplasmic localisation), the same agents increased FLAG-NDR2 activity as assessed by in vitro protein kinase assays, indicative of FLAG-NDR2(Ser-282/Thr-442) phosphorylation. Calyculin A-induced phosphorylation of NDR1(Thr-444)/NDR2(Thr-442) and activation of FLAG-NDR2 were inhibited by staurosporine, but not by other protein kinase inhibitors tested. In ex vivo rat hearts, NDR1(Thr-444)/NDR2(Thr-442) were phosphorylated in response to ischaemia-reperfusion or calyculin A. From a pathological viewpoint, we conclude that activities of NDR1 and NDR2 are responsive to cytotoxic stresses in heart preparations and this may represent a previously-unidentified response to myocardial ischaemia in vivo

Coupling Strongly, Discretely PHYSICS

PERSPECTIVES tein p53 for degradation, show that Mdm2 inhibition can be attained by blocking interaction with its substrate. Yang et al. show that a stable complex forms between TRAF6 and Akt, suggesting that this approach may be a good way to block TRAF6-mediated Akt activation. The potential effectiveness of this approach for tumor therapy is highlighted by the point in the signaling cascade at which TRAF6 contributes to Akt activation-downstream of common mutations observed in the clinic that affect phosphatidylinositol 3-kinase (PI3K) or the phosphatase PTEN, both of which cause hyperactivation of Akt. In support of this, the tumor cell line depleted of TRAF6 that was injected into mice by Yang et al. did not express PTEN and displayed strong Akt activation. TRAF6 could be used to augment the effectiveness of rapamycin analogs (rapalogs), drugs that inhibit the mammalian target of rapamycin complex 1 (mTORC1). Rapalogs are approved for limited antitumor therapy because they may temporarily stabilize tumors in clinical trials but rarely elicit a full response in terms of tumor ablation. Preclinical studies indicate that rapalogs have a cytostatic effect on tumors, due at least in part to increased Akt activation, because a negative feedback loop that normally prevents PI3K signaling is lost. As Yang et al. show, cells lacking TRAF6 display increased spontaneous apoptosis (programmed cell death). Thus, TRAF6 inhibition in conjunction with rapalogs could shift the response of tumors to rapalogs from cytostatic to cytotoxic, increasing the effi cacy of these drugs in cancer therapy. LoPiccolo et al., Drug Resist. Updat. 11, 32 (2008). 4. S. Klein, A. Levitzki, Curr. Opin. Cell Biol. 21, 185 (2009). 5. W.-L. Yang et al., Science 325, 1134). 6. N. Filippa, C. L. Sable, B. A. Hemmings, E. Van Obberghen, Mol. Cell. Biol. 20, 5712 (2000. 7. C. C. Thomas et al., Curr. Biol. 12, 125

Investigating hydrological contributions to volcano monitoring signals. A time-lapse gravity example

Geophysical techniques are widely used to monitor volcanic unrest. A number of studies have also demonstrated that hydrological processes can produce or trigger geophysical signals. Hydrologically-induced gravity signals have previously been recorded by specifically designed gravity surveys as well as, inadvertently, by volcano monitoring studies. Water table corrections of microgravity surveys are commonplace. However, the fluctuations of the water table beneath survey locations are often poorly known, and such a correction fails to account of changes in water-mass storage in the unsaturated zone. Here, we combine 2D axis-symmetrical numerical fluid-flow models with an axis-symmetric, distributed-mass, gravity calculation to model gravity changes in response to fluctuating hydrological recharge. Flow simulations are based on tropical volcanic settings where high surface permeabilities promote thick unsaturated zones. Our study highlights that mass storage (saturation) changes within the unsaturated zone beneath a survey point can generate recordable gravity changes. We show that for a tropical climate, recharge variations can generate gravity variations of over 150 μGal; although, we demonstrate that for the scenarios investigated here, the probability of recording such large signals, is low. Our modelling results indicate that microgravity survey corrections based on water table elevation may result in errors of up to 100 μGal. The effect of inter-annual recharge fluctuations dominate over seasonal cycles which makes prediction and correction of the hydrological contribution more difficult. Spatial hydrogeological heterogeneity can also impact on the accuracy of relative gravity surveys, and can even result in the introduction of additional survey errors. The loading fluctuations associated with saturation variations in the unsaturated zone may also have implications for other geophysical monitoring techniques, such as geodetic monitoring of ground deformation

Exploring views on satisfaction with life in young children with chronic illness: an innovative approach to the collection of self-report data from children under 11

The objective of this study was to explore young children’s views on the impact of chronic illness on their life in order to inform future development of a patient-based self-report health outcome measure. We describe an approach to facilitating self-report views from young children with chronic illness. A board game was designed in order to obtain qualitative data from 39 children with a range of chronic illness conditions and 38 healthy controls ranging in age from 3 to 11 years. The format was effective in engaging young children in a self-report process of determining satisfaction with life and identified nine domains. The board game enabled children aged 5–11 years with chronic illness to describe the effects of living with illness on home, family, friends, school and life in general. It generated direct, non-interpreted material from children who, because of their age, may have been considered unable or limited their ability to discuss and describe how they feel. Obtaining this information for children aged 4 and under continues to be a challenge

The racist bodily imaginary: the image of the body-in-pieces in (post)apartheid culture

This paper outlines a reoccurring motif within the racist imaginary of (post)apartheid culture: the black body-in-pieces. This disturbing visual idiom is approached from three conceptual perspectives. By linking ideas prevalent in Frantz Fanon’s description of colonial racism with psychoanalytic concepts such as Lacan’s notion of the corps morcelé, the paper offers, firstly, an account of the black body-in-pieces as fantasmatic preoccupation of the (post)apartheid imaginary. The role of such images is approached, secondly, through the lens of affect theory which eschews a representational ‘reading’ of such images in favour of attention to their asignifying intensities and the role they play in effectively constituting such bodies. Lastly, Judith Butler’s discussion of war photography and the conditions of grievability introduces an ethical dimension to the discussion and helps draw attention to the unsavory relations of enjoyment occasioned by such images