A framework for optimization of diffusion-weighted MRI protocols for large field-of-view abdominal-pelvic imaging in multicenter studies.

PURPOSE: To develop methods for optimization of diffusion-weighted MRI (DW-MRI) in the abdomen and pelvis on 1.5 T MR scanners from three manufacturers and assess repeatability of apparent diffusion coefficient (ADC) estimates in a temperature-controlled phantom and abdominal and pelvic organs in healthy volunteers. METHODS: Geometric distortion, ghosting, fat suppression, and repeatability and homogeneity of ADC estimates were assessed using phantoms and volunteers. Healthy volunteers (ten per scanner) were each scanned twice on the same scanner. One volunteer traveled to all three institutions in order to provide images for qualitative comparison. The common volunteer was excluded from quantitative analysis of the data from scanners 2 and 3 in order to ensure statistical independence, giving n = 10 on scanner 1 and n = 9 on scanners 2 and 3 for quantitative analysis. Repeatability and interscanner variation of ADC estimates in kidneys, liver, spleen, and uterus were assessed using within-patient coefficient of variation (wCV) and Kruskal-Wallis tests, respectively. RESULTS: The coefficient of variation of ADC estimates in the temperature-controlled phantom was 1%-4% for all scanners. Images of healthy volunteers from all scanners showed homogeneous fat suppression and no marked ghosting or geometric distortion. The wCV of ADC estimates was 2%-4% for kidneys, 3%-7% for liver, 6%-9% for spleen, and 7%-10% for uterus. ADC estimates in kidneys, spleen, and uterus showed no significant difference between scanners but a significant difference was observed in liver (p < 0.05). CONCLUSIONS: DW-MRI protocols can be optimized using simple phantom measurements to produce good quality images in the abdomen and pelvis at 1.5 T with repeatable quantitative measurements in a multicenter study

A disk of dust and molecular gas around a high-mass protostar

The processes leading to the birth of low-mass stars such as our Sun have been well studied, but the formation of high-mass (> 8 x Sun's mass) stars has heretofore remained poorly understood. Recent observational studies suggest that high-mass stars may form in essentially the same way as low-mass stars, namely via an accretion process, instead of via merging of several low-mass (< 8 Msun) stars. However, there is as yet no conclusive evidence. Here, we report the discovery of a flattened disk-like structure observed at submillimeter wavelengths, centered on a massive 15 Msun protostar in the Cepheus-A region. The disk, with a radius of about 330 astronomical units (AU) and a mass of 1 to 8 Msun, is detected in dust continuum as well as in molecular line emission. Its perpendicular orientation to, and spatial coincidence with the central embedded powerful bipolar radio jet, provides the best evidence yet that massive stars form via disk accretion in direct analogy to the formation of low-mass stars

Diffuse Gamma Rays: Galactic and Extragalactic Diffuse Emission

"Diffuse" gamma rays consist of several components: truly diffuse emission from the interstellar medium, the extragalactic background, whose origin is not firmly established yet, and the contribution from unresolved and faint Galactic point sources. One approach to unravel these components is to study the diffuse emission from the interstellar medium, which traces the interactions of high energy particles with interstellar gas and radiation fields. Because of its origin such emission is potentially able to reveal much about the sources and propagation of cosmic rays. The extragalactic background, if reliably determined, can be used in cosmological and blazar studies. Studying the derived "average" spectrum of faint Galactic sources may be able to give a clue to the nature of the emitting objects.Comment: 32 pages, 28 figures, kapproc.cls. Chapter to the book "Cosmic Gamma-Ray Sources," to be published by Kluwer ASSL Series, Edited by K. S. Cheng and G. E. Romero. More details can be found at http://www.gamma.mpe-garching.mpg.de/~aws/aws.htm

High Energy Neutrino Astronomy: Towards Kilometer-Scale Detectors

Of all high-energy particles, only neutrinos can directly convey astronomical information from the edge of the universe---and from deep inside the most cataclysmic high-energy processes. Copiously produced in high-energy collisions, travelling at the velocity of light, and not deflected by magnetic fields, neutrinos meet the basic requirements for astronomy. Their unique advantage arises from a fundamental property: they are affected only by the weakest of nature's forces (but for gravity) and are therefore essentially unabsorbed as they travel cosmological distances between their origin and us. Many of the outstanding mysteries of astrophysics may be hidden from our sight at all wavelengths of the electromagnetic spectrum because of absorption by matter and radiation between us and the source. For example, the hot dense regions that form the central engines of stars and galaxies are opaque to photons. In other cases, such as supernova remnants, gamma ray bursters, and active galaxies, all of which may involve compact objects or black holes at their cores, the precise origin of the high-energy photons emerging from their surface regions is uncertain. Therefore, data obtained through a variety of observational windows---and especially through direct observations with neutrinos---may be of cardinal importance. In this talk, the scientific goals of high energy neutrino astronomy and the technical aspects of water and ice Cherenkov detectors are examined, and future experimental possibilities, including a kilometer-square deep ice neutrino telescope, are explored.Comment: 13 pages, Latex, 6 postscript figures, uses aipproc.sty and epsf.sty. Talk presented at the International Symposium on High Energy Gamma Ray Astronomy, Heidelberg, June 200

FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function

Diabetes in pregnancy is associated with adverse pregnancy outcomes including preterm birth. Although the mechanisms leading to these pregnancy complications are still poorly understood, aberrant angiogenesis and endothelial dysfunction play a key role. FKBPL and SIRT-1 are critical regulators of angiogenesis, however, their roles in pregnancies affected by diabetes have not been examined before in detail. Hence, this study aimed to investigate the role of FKBPL and SIRT-1 in pre-gestational (type 1 diabetes mellitus, T1D) and gestational diabetes mellitus (GDM). Placental protein expression of important angiogenesis proteins, FKBPL, SIRT-1, PlGF and VEGF-R1, was determined from pregnant women with GDM or T1D, and in the first trimester trophoblast cells exposed to high glucose (25 mM) and varying oxygen concentrations [21%, 6.5%, 2.5% (ACH-3Ps)]. Endothelial cell function was assessed in high glucose conditions (30 mM) and following FKBPL overexpression. Placental FKBPL protein expression was downregulated in T1D (FKBPL; p<0.05) whereas PlGF/VEGF-R1 were upregulated (p<0.05); correlations adjusted for gestational age were also significant. In the presence of GDM, only SIRT-1 was significantly downregulated (p<0.05) even when adjusted for gestational age (r=-0.92, p=0.001). Both FKBPL and SIRT-1 protein expression was reduced in ACH-3P cells in high glucose conditions associated with 6.5%/2.5% oxygen concentrations compared to experimental normoxia (21%; p<0.05). FKBPL overexpression in endothelial cells (HUVECs) exacerbated reduction in tubule formation compared to empty vector control, in high glucose conditions (junctions; p<0.01, branches; p<0.05). In conclusion, FKBPL and/or SIRT-1 downregulation in response to diabetic pregnancies may have a key role in the development of vascular dysfunction and associated complications affected by impaired placental angiogenesis

Gravitational Radiation from Post-Newtonian Sources and Inspiralling Compact Binaries

The article reviews the current status of a theoretical approach to the problem of the emission of gravitational waves by isolated systems in the context of general relativity. Part A of the article deals with general post-Newtonian sources. The exterior field of the source is investigated by means of a combination of analytic post-Minkowskian and multipolar approximations. The physical observables in the far-zone of the source are described by a specific set of radiative multipole moments. By matching the exterior solution to the metric of the post-Newtonian source in the near-zone we obtain the explicit expressions of the source multipole moments. The relationships between the radiative and source moments involve many non-linear multipole interactions, among them those associated with the tails (and tails-of-tails) of gravitational waves. Part B of the article is devoted to the application to compact binary systems. We present the equations of binary motion, and the associated Lagrangian and Hamiltonian, at the third post-Newtonian (3PN) order beyond the Newtonian acceleration. The gravitational-wave energy flux, taking consistently into account the relativistic corrections in the binary moments as well as the various tail effects, is derived through 3.5PN order with respect to the quadrupole formalism. The binary's orbital phase, whose prior knowledge is crucial for searching and analyzing the signals from inspiralling compact binaries, is deduced from an energy balance argument.Comment: 109 pages, 1 figure; this version is an update of the Living Review article originally published in 2002; available on-line at http://www.livingreviews.org

Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.

ContextPreeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.ObjectiveTo investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44.Design and interventionFKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling.Settings and participantsHuman samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid.Main outcome measuresPreeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signaling in trophoblast and endothelial cells were assessed.ResultsThe CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, P = 0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signaling, enhancing cell angiogenesis.ConclusionsThe FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes

Association between Plasma Antibody Response and Protection in Rainbow Trout Oncorhynchus mykiss Immersion Vaccinated against Yersinia ruckeri

A key hallmark of the vertebrate adaptive immune system is the generation of antigen-specific antibodies from B cells. Fish are the most primitive gnathostomes (jawed vertebrates) possessing an adaptive immune system. Vaccination of rainbow trout against enteric redmouth disease (ERM) by immersion in Yersinia ruckeri bacterin confers a high degree of protection to the fish. The immune mechanisms responsible for protection may comprise both cellular and humoral elements but the role of specific immunoglobulins in this system has been questioned and not previously described. The present study demonstrates significant increase in plasma antibody titers following immersion vaccination and significantly reduced mortality during Y. ruckeri challenge

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care