Fetal in vivo continuous cardiovascular function during chronic hypoxia.

Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean P(aO2) levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery during the last third of gestation. The ratio of oxygen (from 2.7 ± 0.2 to 3.8 ± 0.8; P < 0.05) and of glucose (from 2.3 ± 0.1 to 3.3 ± 0.6; P < 0.05) delivery to the fetal carotid, relative to the fetal femoral circulation, increased during and shortly after the period of chronic hypoxia. In contrast, oxygen and glucose delivery remained unchanged from baseline in normoxic fetuses. Fetal plasma urate concentration increased significantly during chronic hypoxia but not during normoxia (Δ: 4.8 ± 1.6 vs. 0.5 ± 1.4 μmol l(-1), P<0.05). The data support the hypotheses tested and show persisting redistribution of substrate delivery away from peripheral and towards essential circulations in the chronically hypoxic fetus, associated with increases in xanthine oxidase-derived reactive oxygen species.This work was supported by the British Heart Foundation.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1113/JP27109

Quality of life support in advanced cancer – Web and technological interventions: systematic review and narrative synthesis

Background As treatments continue to progress, patients with advanced cancer are living longer. However, ongoing physical side-effects and psychosocial concerns can compromise quality of life (QoL). Patients and physicians increasingly look to the internet and other technologies to address diverse supportive needs encountered across this evolving cancer trajectory. Objectives 1. To examine the features and delivery of web and technological interventions supporting patients with advanced cancer. 2. To explore their efficacy relating to QoL and psychosocial well-being. Methods Relevant studies were identified through electronic database searches (MEDLINE, PsychINFO, Embase, CINAHL, CENTRAL, Web of Science and ProQuest) and handsearching. Findings were collated and explored through narrative synthesis. Results Of 5274 identified records, 37 articles were included. Interventions were evaluated within studies targeting advanced cancer (13) or encompassing all stages (24). Five subtypes emerged: Interactive Health Communication Applications (n=12), virtual programmes of support (n=11), symptom monitoring tools (n=8), communication conduits (n=3) and information websites (n=3). Modes of delivery ranged from self-management to clinically integrated. Support largely targeted psychosocial well-being, alongside symptom management and healthy living. Most studies (78%) evidenced varying degrees of efficacy through QoL and psychosocial measures. Intervention complexity made it challenging to distinguish the most effective components. Incomplete reporting limited risk of bias assessment. Conclusion While complex and varied in their content, features and delivery, most interventions led to improvements in QoL or psychosocial well-being across the cancer trajectory. Ongoing development and evaluation of such innovations should specifically target patients requiring longer-term support for later-stage cancer

Dark Matter, Muon g-2 and Other SUSY Constraints

Recent developments constraining the SUSY parameter space are reviewed within the framework of SUGRA GUT models. The WMAP data is seen to reduce the error in the density of cold dark matter by about a factor of four, implying that the lightest stau is only 5 -10 GeV heavier than the lightest neutralino when m_0, m_{1/2} < 1 TeV. The CMD-2 re-analysis of their data has reduced the disagreement between the Standard Model prediction and the Brookhaven measurement of the muon magnetic moment to 1.9 sigma, while using the tau decay data plus CVC, the disagreement is 0.7 sigma. (However, the two sets of data remain inconsistent at the 2.9 sigma level.) The recent Belle and BABAR measurements of the B -> phi K CP violating parameters and branching ratios are discussed. They are analyzed theoretically within the BBNS improved factorization method. The CP parameters are in disagreement with the Standard Model at the 2.7 sigma level, and the branching ratios are low by a factor of two or more over most of the parameter space. It is shown that both anomalies can naturally be accounted for by adding a non-universal cubic soft breaking term at M_G mixing the second and third generations.Comment: 16 pages, 7 figures, plenary talk at Beyond The Desert '03, Castle Ringberg, Germany, June 9, 2003. Typos correcte

Enhanced mitochondrial superoxide scavenging does not Improve muscle insulin action in the high fat-fed mouse

Improving mitochondrial oxidant scavenging may be a viable strategy for the treatment of insulin resistance and diabetes. Mice overexpressing the mitochondrial matrix isoform of superoxide dismutase (sod2(tg) mice) and/or transgenically expressing catalase within the mitochondrial matrix (mcat(tg) mice) have increased scavenging of O2(˙-) and H2O2, respectively. Furthermore, muscle insulin action is partially preserved in high fat (HF)-fed mcat(tg) mice. The goal of the current study was to test the hypothesis that increased O2(˙-) scavenging alone or in combination with increased H2O2 scavenging (mtAO mice) enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was examined in conscious, unrestrained and unstressed wild type (WT), sod2(tg), mcat(tg) and mtAO mice using hyperinsulinemic-euglycemic clamps (insulin clamps) combined with radioactive glucose tracers following sixteen weeks of normal chow or HF (60% calories from fat) feeding. Glucose infusion rates, whole body glucose disappearance, and muscle glucose uptake during the insulin clamp were similar in chow- and HF-fed WT and sod2(tg) mice. Consistent with our previous work, HF-fed mcat(tg) mice had improved muscle insulin action, however, an additive effect was not seen in mtAO mice. Insulin-stimulated Akt phosphorylation in muscle from clamped mice was consistent with glucose flux measurements. These results demonstrate that increased O2(˙-) scavenging does not improve muscle insulin action in the HF-fed mouse alone or when coupled to increased H2O2 scavenging

Multivariate characterization of white matter heterogeneity in autism spectrum disorder

The complexity and heterogeneity of neuroimaging findings in individuals with autism spectrum disorder has suggested that many of the underlying alterations are subtle and involve many brain regions and networks. The ability to account for multivariate brain features and identify neuroimaging measures that can be used to characterize individual variation have thus become increasingly important for interpreting and understanding the neurobiological mechanisms of autism. In the present study, we utilize the Mahalanobis distance, a multidimensional counterpart of the Euclidean distance, as an informative index to characterize individual brain variation and deviation in autism. Longitudinal diffusion tensor imaging data from 149 participants (92 diagnosed with autism spectrum disorder and 57 typically developing controls) between 3.1 and 36.83 years of age were acquired over a roughly 10-year period and used to construct the Mahalanobis distance from regional measures of white matter microstructure. Mahalanobis distances were significantly greater and more variable in the autistic individuals as compared to control participants, demonstrating increased atypicalities and variation in the group of individuals diagnosed with autism spectrum disorder. Distributions of multivariate measures were also found to provide greater discrimination and more sensitive delineation between autistic and typically developing individuals than conventional univariate measures, while also being significantly associated with observed traits of the autism group. These results help substantiate autism as a truly heterogeneous neurodevelopmental disorder, while also suggesting that collectively considering neuroimaging measures from multiple brain regions provides improved insight into the diversity of brain measures in autism that is not observed when considering the same regions separately. Distinguishing multidimensional brain relationships may thus be informative for identifying neuroimaging-based phenotypes, as well as help elucidate underlying neural mechanisms of brain variation in autism spectrum disorders

Naturalness and Fine Tuning in the NMSSM: Implications of Early LHC Results

We study the fine tuning in the parameter space of the semi-constrained NMSSM, where most soft Susy breaking parameters are universal at the GUT scale. We discuss the dependence of the fine tuning on the soft Susy breaking parameters M_1/2 and m0, and on the Higgs masses in NMSSM specific scenarios involving large singlet-doublet Higgs mixing or dominant Higgs-to-Higgs decays. Whereas these latter scenarios allow a priori for considerably less fine tuning than the constrained MSSM, the early LHC results rule out a large part of the parameter space of the semi-constrained NMSSM corresponding to low values of the fine tuning.Comment: 19 pages, 10 figures, bounds from Susy searches with ~1/fb include

Hidden SUSY at the LHC: the light higgsino-world scenario and the role of a lepton collider

While the SUSY flavor, CP and gravitino problems seem to favor a very heavy spectrum of matter scalars, fine-tuning in the electroweak sector prefers low values of superpotential mass \mu. In the limit of low \mu, the two lightest neutralinos and light chargino are higgsino-like. The light charginos and neutralinos may have large production cross sections at LHC, but since they are nearly mass degenerate, there is only small energy release in three-body sparticle decays. Possible dilepton and trilepton signatures are difficult to observe after mild cuts due to the very soft p_T spectrum of the final state isolated leptons. Thus, the higgsino-world scenario can easily elude standard SUSY searches at the LHC. It should motivate experimental searches to focus on dimuon and trimuon production at the very lowest p_T(\mu) values possible. If the neutralino relic abundance is enhanced via non-standard cosmological dark matter production, then there exist excellent prospects for direct or indirect detection of higgsino-like WIMPs. While the higgsino-world scenario may easily hide from LHC SUSY searches, a linear e^+e^- collider or a muon collider operating in the \sqrt{s}\sim 0.5-1 TeV range would be able to easily access the chargino and neutralino pair production reactions.Comment: 20 pages including 12 .eps figure

Building for the future: essential infrastructure for rodent ageing studies

When planning ageing research using rodent models, the logistics of supply, long term housing and infrastructure provision are important factors to take into consideration. These issues need to be prioritised to ensure they meet the requirements of experiments which potentially will not be completed for several years. Although these issues are not unique to this discipline, the longevity of experiments and indeed the animals, requires a high level of consistency and sustainability to be maintained throughout lengthy periods of time. Moreover, the need to access aged stock or material for more immediate experiments poses many issues for the completion of pilot studies and/or short term intervention studies on older models. In this article, we highlight the increasing demand for ageing research, the resources and infrastructure involved, and the need for large-scale collaborative programmes to advance studies in both a timely and a cost-effective way