Quantification of the severity of hypoxic-ischemic brain injury in a neonatal preclinical model using measurements of cytochrome-c-oxidase from a miniature broadband-near-infrared spectroscopy system

We describe the development of a miniaturized broadband near-infrared spectroscopy system (bNIRS), which measures changes in cerebral tissue oxyhemoglobin (  [  HbO₂ ]  ) and deoxyhemoglobin ([HHb]) plus tissue metabolism via changes in the oxidation state of cytochrome-c-oxidase ([oxCCO]). The system is based on a small light source and a customized mini-spectrometer. We assessed the instrument in a preclinical study in 27 newborn piglets undergoing transient cerebral hypoxia-ischemia (HI). We aimed to quantify the recovery of the HI insult and estimate the severity of the injury. The recovery in brain oxygenation (Δ  [  HbDiff  ]    =  Δ  [  HbO₂  ]    −  Δ  [  HHb  ]  ), blood volume (Δ  [  HbT  ]    =  Δ  [  HbO₂  ]    +  Δ  [  HHb  ]  ), and metabolism (Δ  [  oxCCO  ]  ) for up to 30 min after the end of HI were quantified in percentages using the recovery fraction (RF) algorithm, which quantifies the recovery of a signal with respect to baseline. The receiver operating characteristic analysis was performed on bNIRS-RF measurements compared to proton (H1) magnetic resonance spectroscopic (MRS)-derived thalamic lactate/N-acetylaspartate (Lac/NAA) measured at 24-h post HI insult; Lac/NAA peak area ratio is an accurate surrogate marker of neurodevelopmental outcome in babies with neonatal HI encephalopathy. The Δ  [  oxCCO  ]  -RF cut-off threshold of 79% within 30 min of HI predicted injury severity based on Lac/NAA with high sensitivity (100%) and specificity (93%). A significant difference in thalamic Lac/NAA was noticed (p  <  0.0001) between the two groups based on this cut-off threshold of 79% Δ  [  oxCCO  ]  -RF. The severe injury group (n  =  13) had ∼30  %   smaller recovery in Δ  [  HbDiff  ]  -RF (p  =  0.0001) and no significant difference was observed in Δ  [  HbT  ]  -RF between groups. At 48 h post HI, significantly higher P31-MRS-measured inorganic phosphate/exchangeable phosphate pool (epp) (p  =  0.01) and reduced phosphocreatine/epp (p  =  0.003) were observed in the severe injury group indicating persistent cerebral energy depletion. Based on these results, the bNIRS measurement of the oxCCO recovery fraction offers a noninvasive real-time biomarker of brain injury severity within 30 min following HI insult

The CMS Tracker Readout Front End Driver

The Front End Driver, FED, is a 9U 400mm VME64x card designed for reading out the Compact Muon Solenoid, CMS, silicon tracker signals transmitted by the APV25 analogue pipeline Application Specific Integrated Circuits. The FED receives the signals via 96 optical fibers at a total input rate of 3.4 GB/sec. The signals are digitized and processed by applying algorithms for pedestal and common mode noise subtraction. Algorithms that search for clusters of hits are used to further reduce the input rate. Only the cluster data along with trigger information of the event are transmitted to the CMS data acquisition system using the S-LINK64 protocol at a maximum rate of 400 MB/sec. All data processing algorithms on the FED are executed in large on-board Field Programmable Gate Arrays. Results on the design, performance, testing and quality control of the FED are presented and discussed

Systems Biology Model of Cerebral Oxygen Delivery and Metabolism During Therapeutic Hypothermia: Application to the Piglet Model

Hypoxic ischaemic encephalopathy (HIE) is a significant cause of death and disability. Therapeutic hypothermia (TH) is the only available standard of treatment, but 45-55% of cases still result in death or neurodevelopmental disability following TH. This work has focussed on developing a new brain tissue physiology and biochemistry systems biology model that includes temperature effects, as well as a Bayesian framework for analysis of model parameter estimation. Through this, we can simulate the effects of temperature on brain tissue oxygen delivery and metabolism, as well as analyse clinical and experimental data to identify mechanisms to explain differing behaviour and outcome. Presented here is an application of the model to data from two piglets treated with TH following hypoxic-ischaemic injury showing different responses and outcome following treatment. We identify the main mechanism for this difference as the Q10 temperature coefficient for metabolic reactions, with the severely injured piglet having a median posterior value of 0.133 as opposed to the mild injury value of 5.48. This work demonstrates the use of systems biology models to investigate underlying mechanisms behind the varying response to hypothermic treatment

The effect of management for red grouse shooting on the population density of breeding birds on heather-dominated moorland.

Summary 1. Breeding birds, vegetation and moorland management were surveyed in 320 1-km squares on 122 estates in upland areas of eastern Scotland and northern England where red grouse shooting is a widespread land use. We assessed whether population densities of eleven species of breeding birds differed between heather-dominated moorland managed for red grouse shooting and other moorland with similar vegetation. 2. We classified estates which had a full-time equivalent moorland gamekeeper as grouse moors. The mean density of red grouse shot per year was four times higher and the mean density of gamekeepers was three times higher on grouse moors than on other moors. Rotational burning of ground vegetation covered a 34% larger area on grouse moors than on other moors. 3. Selection of heather-dominated squares resulted in similar composition of vegetation on grouse moors and other moors (about 76% heath, 12% grass, 8% bog, 2% flush and &lt;1% bracken on both types). However, grouse moors tended to have less tall vegetation than other moors and differed significantly in some other characteristics of the vegetation, topography and soil type. 4. Densities of breeding golden plover and lapwing were five times higher and those of red grouse and curlew were twice as high on grouse moors as on other moors, whilst meadow pipit, skylark, whinchat and carrion/hooded crow were 1.5, 2.3, 3.9 and 3.1 times less abundant, respectively, on grouse moors. The differences in density between moorland types remained significant (P &lt; 0.001) 2. Grouse moor management and breeding birds for golden plover and crow and approached significance (P &lt; 0.10) for lapwing and meadow pipit after allowing for variation among regions. 5. We used Poisson regression models to relate bird density to vegetation cover, topography, climate and soil type. After adjusting for significant effects of these habitat variables, significant differences in bird density between the two moorland types remained for six species, though their magnitude was reduced. 6. Correlations of adjusted bird density with measures of different aspects of grouse moor management provided evidence of a possible positive influence of predator control (assessed using crow density) on red grouse, golden plover and lapwing. The control of crows by gamekeepers is the most likely cause of the low densities of crows on grouse moors. There was evidence of a positive effect of heather burning on the density of red grouse and golden plover and a negative effect on meadow pipit. Multiple Poisson regression indicated that predator control and heather burning had significant separate effects on red grouse density. Significant relationships between adjusted breeding bird densities and the abundance of raptors and ravens were few and predominantly positive. 7. The results provide correlative evidence that moorland management benefits some breeding bird species and disbenefits others in ways that cannot readily be explained away as effects of differences in vegetation type or topography. However, experimental manipulations of numbers of some predators and heather burning are required to test these findings

Moving from atheoretical to theoretical approaches to interprofessional client-centred collaborative practice

In this chapter we revisit the importance of theory in the development of interprofessional client centred education and practice (IPCEP). We focus specifically on the theoretical underpinnings and development of a workshop model aimed at moving practitioners from atheoretical to theoretical collaborative practice

Knowledge politics and new converging technologies: a social epistemological perspective

The “new converging technologies” refers to the prospect of advancing the human condition by the integrated study and application of nanotechnology, biotechnology, information technology and the cognitive sciences - or “NBIC”. In recent years, it has loomed large, albeit with somewhat different emphases, in national science policy agendas throughout the world. This article considers the political and intellectual sources - both historical and contemporary - of the converging technologies agenda. Underlying it is a fluid conception of humanity that is captured by the ethically challenging notion of “enhancing evolution”

Inhaled 45-50% argon augments hypothermic brain protection in a piglet model of perinatal asphyxia

Cooling to 33.5 °C in babies with neonatal encephalopathy significantly reduces death and disability, however additional therapies are needed to maximize brain protection. Following hypoxia–ischemia we assessed whether inhaled 45–50% Argon from 2–26 h augmented hypothermia neuroprotection in a neonatal piglet model, using MRS and aEEG, which predict outcome in babies with neonatal encephalopathy, and immunohistochemistry. Following cerebral hypoxia–ischemia, 20 Newborn male Large White piglets < 40 h were randomized to: (i) Cooling (33 °C) from 2–26 h (n = 10); or (ii) Cooling and inhaled 45–50% Argon (Cooling + Argon) from 2–26 h (n = 8). Whole-brain phosphorus-31 and regional proton MRS were acquired at baseline, 24 and 48 h after hypoxia–ischemia. EEG was monitored. At 48 h after hypoxia–ischemia, cell death (TUNEL) was evaluated over 7 brain regions. There were no differences in body weight, duration of hypoxia–ischemia or insult severity; throughout the study there were no differences in heart rate, arterial blood pressure, blood biochemistry and inotrope support. Two piglets in the Cooling + Argon group were excluded. Comparing Cooling + Argon with Cooling there was preservation of whole-brain MRS ATP and PCr/Pi at 48 h after hypoxia–ischemia (p < 0.001 for both) and lower 1H MRS lactate/N acetyl aspartate in white (p = 0.03 and 0.04) but not gray matter at 24 and 48 h. EEG background recovery was faster (p < 0.01) with Cooling + Argon. An overall difference between average cell-death of Cooling versus Cooling + Argon was observed (p < 0.01); estimated cells per mm2 were 23.9 points lower (95% C.I. 7.3–40.5) for the Cooling + Argon versus Cooling. Inhaled 45–50% Argon from 2–26 h augmented hypothermic protection at 48 h after hypoxia–ischemia shown by improved brain energy metabolism on MRS, faster EEG recovery and reduced cell death on TUNEL. Argon may provide a cheap and practical therapy to augment cooling for neonatal encephalopathy

Square-tiled cyclic covers

A cyclic cover of the complex projective line branched at four appropriate points has a natural structure of a square-tiled surface. We describe the combinatorics of such a square-tiled surface, the geometry of the corresponding Teichm\"uller curve, and compute the Lyapunov exponents of the determinant bundle over the Teichm\"uller curve with respect to the geodesic flow. This paper includes a new example (announced by G. Forni and C. Matheus in \cite{Forni:Matheus}) of a Teichm\"uller curve of a square-tiled cyclic cover in a stratum of Abelian differentials in genus four with a maximally degenerate Kontsevich--Zorich spectrum (the only known example found previously by Forni in genus three also corresponds to a square-tiled cyclic cover \cite{ForniSurvey}). We present several new examples of Teichm\"uller curves in strata of holomorphic and meromorphic quadratic differentials with maximally degenerate Kontsevich--Zorich spectrum. Presumably, these examples cover all possible Teichm\"uller curves with maximally degenerate spectrum. We prove that this is indeed the case within the class of square-tiled cyclic covers.Comment: 34 pages, 6 figures. Final version incorporating referees comments. In particular, a gap in the previous version was corrected. This file uses the journal's class file (jmd.cls), so that it is very similar to published versio

Why Are People's Decisions Sometimes Worse with Computer Support?

In many applications of computerised decision support, a recognised source of undesired outcomes is operators' apparent over-reliance on automation. For instance, an operator may fail to react to a potentially dangerous situation because a computer fails to generate an alarm. However, the very use of terms like "over-reliance" betrays possible misunderstandings of these phenomena and their causes, which may lead to ineffective corrective action (e.g. training or procedures that do not counteract all the causes of the apparently "over-reliant" behaviour). We review relevant literature in the area of "automation bias" and describe the diverse mechanisms that may be involved in human errors when using computer support. We discuss these mechanisms, with reference to errors of omission when using "alerting systems", with the help of examples of novel counterintuitive findings we obtained from a case study in a health care application, as well as other examples from the literature

Delayed presentation of an isolated gallbladder rupture following blunt abdominal trauma: a case report

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