Whole works, to which is prefixed, A life of the author,

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Increased mononuclear cell activation and apoptosis early after human liver transplantation is associated with a reduced frequency of acute rejection

Experimental models of orthotopic liver transplantation (OLT) have shown that the very early events post-OLT are critical in distinguishing immunogenic and tolerogenic reactions. In rodents, increased leukocyte apoptosis and cytokine expression have been demonstrated in tolerogenic strain combinations. Information from human OLT recipients is less abundant. The aim of this study was to determine the amount of early leukocyte activation and apoptosis following human OLT, and to correlate this with subsequent rejection status. Peripheral blood mononuclear cells (PBMC) were isolated from 76 patients undergoing OLT - on the day prior, 5 hrs after reperfusion (day 0), and 18-24 hrs post-OLT (day 1). The mean level of apoptotic PBMCs on post OLT day 1 was higher than healthy recipients (0.9% +/- 0.2 vs. 0.2% +/- 0.1, p = 0.013). Apoptosis was greater in nonrejecting (NR) (1.1% +/- 0.3) compared with acutely-rejecting (R) (0.3% +/- 0.1, p = 0.021) patients. On day 1, PBMC from NR patients had increased expression of IFN-gamma (p = 0.006), IL-10 (p = 0.016), and CD40 ligand (p = 0.02) compared with R. Donor cell chimerism on day 1 did not differ between the groups indicating that this was unlikely to account for increased PBMC apoptosis in the NR group. Interestingly, the level of chimerism on day 0 was significantly higher in NR (3.8% +/- 0.6) compared with R (1.2% +/- 0.4, p = 0.004) patients and there was a close correlation between chimerism on day 0 and cytokine expression on day 1. These results imply that similar mechanisms are occurring in the human liver to promote graft acceptance as in the experimental models of liver transplantation and suggest that strategies that promote liver transplant acceptance in rodents might be applicable to humans.

Volcanic resurfacing and the early terrestrial crust: Zircon U-Pb and REE constraints from the Isua Greenstone Belt, southern West Greenland

The oldest known bona fide succession of elastic metasediments Occurs in the Isua Greenstone Belt. SW Greenland and consists of a variety of mica schists and rare metaconglomerates. The metasediments are in direct contact with a felsic metavolcanic lithology that has previously been dated to 3.71 Ga. Based on trace element geochemical data for 30 metasediments, we selected the six samples with highest Zr concentrations for zircon extraction. These samples all yielded very few or no zircon, Those extracted from mica schists yielded ion probe U/Pb ages between 3.70 and 3,71 Ga. One metaconglomerate sample yielded just a single zircon of 3.74 Ga age. The mica schist hosted zircons have U/Pb ages. Th/U ratios, REE patterns and Eu anomalies indistinguishable from zircon in the adjacent 3.71 Ga felsic metavolcanic unit. Trace element modelling requires the bulk of material in the metasediments to be derived from variably weathered mafic lithologies but some metasediments contain substantial contribution from more evolved source lithologies. The paucity of zircon in the mica schists is thus explained by incorporation of material from largely zircon-free volcanic lithologies. The absence of older zircon in the mica schists and the preponderance of mafic source material imply intense, mainly basaltic resurfacing of the early Earth. The implications of this process are discussed, Thermal considerations suggest that horizontal growth of Hadean crust by addition of mafic ultramafic lavas must have triggered self-reorganisation of the protocrust by remelting. Reworking oft Hadean crust may have been aided by burial of hydrated (weathered) metabasalt due to semi-continuous addition of new voluminous basalt Outpouring,;, This process Causes a bias towards eruption of Zr-saturated partial melts at the surface with O-isotope corn posit ion,, potentially different from the mantle. The oldest zircons hosted in sediments would have been buried to substantial depth or formed in plutons that crystallised at some depth from which it took hundreds of millions of years for them to be exhumed and incorporated into much younger sediments. (C) 2005 Elsevier B.V.All rights reserved.

Comparative susceptibility of indigenous and improved pig breeds to Classical swine fever virus infection: Practical and epidemiological implications in a subsistence-based, developing country setting

This study investigated the comparative susceptibility of indigenous Moo Laat and improved Large White/Landrace pig breeds to infection with classical swine fever virus (CSFV) under controlled conditions in the Lao People's Democratic Republic (Lao PDR). The Moo Laat (ML) and Large White/Landrace crossbreed (LWC) pigs were inoculated with a standard challenge strain designated Lao/Kham225 (infectivity titre of 10(2.75) TCID50/ml). The results demonstrated that both the native breed and an improved pig breed are fully susceptible to CSFV infection and the mortality rate is high. LWC pigs demonstrated lower (or shorter) survival times (50% survival time: 11 days), earlier and higher pyrexia and earlier onset of viraemia compared to ML pigs (50% survival time: 18 days). In the context of village-based pig production, the longer time from infection to death in native ML pigs means that incubating or early sick pigs are likely to be sold once an outbreak of CSF is recognized in a village. This increased longevity probably contributes to the maintenance and spread of disease in a population where generally the contact rate is low.

Does timing and sequencing of transitions to adulthood make a difference? Stress, smoking, and physical activity among young Australian women

The major changes of the transition to adulthood are argued to be stressful, and health-related behaviors such as smoking and physical activity may be adopted, consolidated, or abandoned at this time. On the other hand, research has suggested that the normative transitions of emerging adulthood, although involving considerable change, may be associated with low stress because they are perceived as both positive and normal at this life stage. This article examines relations between the timing and sequencing of life transitions and stress and health-related behaviors, focusing on the transition to young adulthood among Australian women. A total of 853 women aged 22 to 27 provided information about the timing and sequencing of 6 life transitions: moving out of home, stopping full-time education, starting full-time work, having the first live-in relationship, marriage, and motherhood-and stress, smoking, and physical activity. Most had moved out of home, stopped full-time education, and started full-time work, but only 14% had undertaken all 6 transitions. Overall, 70% of participants had made transitions in order Overall, the findings suggest that the relations between timing and sequencing of transitions, and indicators of health, are moderate for smoking, but small for stress and for physical activity. These effects remained after controlling for socioeconomic status of the participants' families of origin. Matching current social norms for the timing and sequencing of life changes may be of less importance for women's well-being than is commonly believed. Although the significant relations between early or out of order transitions and smoking are of concern, the smaller relations with stress and with sedentariness suggest that such transitions may have limited negative consequences, and support the view that individuals are active in choosing the life path that is appropriate for them and their circumstances.

The optimisation of legacy water treatment works to produce a more consistent final water quality

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Ocular changes and other factors relating to two forms of contact lenses:a comparative study

The work utilising a new material for contact lenses has fallen into three parts: Physioloeical considerations: Since the cornea is devoid of blood vessels, its oxygen is derived from the atmosphere. Early hydrophilic gel contact lenses interrupted the flow of oxygen and corneal insult resulted. Three techniques of fenestration were tried to overcome this problem. High speed drilling with 0.1 mm diameter twist drills. was found to be mechanically successful, but under clinical conditions mucous blockage of the fenestrations occurred. An investigation was made into the amount of oxygen arriving at the corneal interface; related to gel lens thickness. The results indicated an improvement in corneal oxygen as lens thickness was reduced. The mechanism is thought to be a form of mechanical pump. A series of clinical studies con:firmed the experimental work; the use of thin lenses removing the symptoms of corneal hypoxia. Design: The parameters of lens back curvature. lens thickness and lens diameter have been isolated and related to three criteria of vision (a) Visual acuity. (b) Visual stability and (c) Induced astigmatism. From the results achieved a revised and basically successful design of lens has been developed. Comparative study: The developed form of lens was compared with traditional lenses in a controlled survey. Twelve factors were assessed over a twenty week period of wear using a total of eighty four patients. The results of this study indicate that whilst the expected changes were noted with the traditional lens wearers, gel lens wearers showed no discernible change in any of the factors measured. ldth the exception of' one parameter. In addition to a description of' the completed l'iork. further investigations are ·sug~ested l'lhich. it is hoped. l'iould further improve the optical performance of gel lenses.

Adaptive responses by mouse early embryos to maternal diet protect fetal growth but predispose to adult onset disease

Poor maternal nutrition during pregnancy can alter postnatal phenotype and increase susceptibility to adult cardiovascular and metabolic diseases. However, underlying mechanisms are largely unknown. Here, we show that maternal low protein diet (LPD), fed exclusively during mouse preimplantation development, leads to offspring with increased weight from birth, sustained hypertension, and abnormal anxiety-related behavior, especially in females. These adverse outcomes were interrelated with increased perinatal weight being predictive of later adult overweight and hypertension. Embryo transfer experiments revealed that the increase in perinatal weight was induced within blastocysts responding to preimplantation LPD, independent of subsequent maternal environment during later pregnancy. We further identified the embryo-derived visceral yolk sac endoderm (VYSE) as one mediator of this response. VYSE contributes to fetal growth through endocytosis of maternal proteins, mainly via the multiligand megalin (LRP2) receptor and supply of liberated amino acids. Thus, LPD maintained throughout gestation stimulated VYSE nutrient transport capacity and megalin expression in late pregnancy, with enhanced megalin expression evident even when LPD was limited to the preimplantation period. Our results demonstrate that in a nutrient-restricted environment, the preimplantation embryo activates physiological mechanisms of developmental plasticity to stablize conceptus growth and enhance postnatal fitness. However, activation of such responses may also lead to adult excess growth and cardiovascular and behavioral diseases. © 2008 by the Society for the Study of Reproduction, Inc.

Evolution, recurrency and kernels in learning to model inflation

This paper provides the most fully comprehensive evidence to date on whether or not monetary aggregates are valuable for forecasting US inflation in the early to mid 2000s. We explore a wide range of different definitions of money, including different methods of aggregation and different collections of included monetary assets. We use non-linear, artificial intelligence techniques, namely, recurrent neural networks, evolution strategies and kernel methods in our forecasting experiment. In the experiment, these three methodologies compete to find the best fitting US inflation forecasting models and are then compared to forecasts from a naive random walk model. The best models were non-linear autoregressive models based on kernel methods. Our findings do not provide much support for the usefulness of monetary aggregates in forecasting inflation. There is evidence in the literature that evolutionary methods can be used to evolve kernels hence our future work should combine the evolutionary and kernel methods to get the benefits of both.

Development of micro immunosensors to study genomic and proteomic biomarkers related to cancer and Alzheimer's disease

A report from the National Institutes of Health defines a disease biomarker as a “characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” Early diagnosis is a crucial factor for incurable disease such as cancer and Alzheimer’s disease (AD). During the last decade researchers have discovered that biochemical changes caused by a disease can be detected considerably earlier as compared to physical manifestations/symptoms. In this dissertation electrochemical detection was utilized as the detection strategy as it offers high sensitivity/specificity, ease of operation, and capability of miniaturization and multiplexed detection. Electrochemical detection of biological analytes is an established field, and has matured at a rapid pace during the last 50 years and adapted itself to advances in micro/nanofabrication procedures. Carbon fiber microelectrodes were utilized as the platform sensor due to their high signal to noise ratio, ease and low-cost of fabrication, biocompatibility, and active carbon surface which allows conjugation with biorecognition moieties. This dissertation specifically focuses on the detection of 3 extensively validated biomarkers for cancer and AD. Firstly, vascular endothelial growth factor (VEGF) a cancer biomarker was detected using a one-step, reagentless immunosensing strategy. The immunosensing strategy allowed a rapid and sensitive means of VEGF detection with a detection limit of about 38 pg/mL with a linear dynamic range of 0–100 pg/mL. Direct detection of AD-related biomarker amyloid beta (Aβ) was achieved by exploiting its inherent electroactivity. The quantification of the ratio of Aβ1-40/42 (or Aβ ratio) has been established as a reliable test to diagnose AD through human clinical trials. Triple barrel carbon fiber microelectrodes were used to simultaneously detect Aβ1-40 and Aβ1-42 in cerebrospinal fluid from rats within a detection range of 100nM to 1.2μM and 400nM to 1μM respectively. In addition, the release of DNA damage/repair biomarker 8-hydroxydeoxyguanine (8-OHdG) under the influence of reactive oxidative stress from single lung endothelial cell was monitored using an activated carbon fiber microelectrode. The sensor was used to test the influence of nicotine, which is one of the most biologically active chemicals present in cigarette smoke and smokeless tobacco.

Subject -centered and problem -based approaches to teaching clinical competence in physical therapy

Physical therapy students must apply the relevant information learned in their academic and clinical experience to problem solve in treating patients. I compared the clinical cognitive competence in patient care of second-year masters students enrolled in two different curricular programs: modified problem-based (M P-B; n = 27) and subject-centered (S-C; n = 41). Main features of S-C learning include lecture and demonstration as the major teaching strategies and no exposure to patients or problem solving learning until the sciences (knowledge) have been taught. Comparatively, main features of M P-B learning include case study in small student groups as the main teaching strategy, early and frequent exposure to patients, and knowledge and problem solving skills learned together for each specific case. Basic and clinical orthopedic knowledge was measured with a written test with open-ended items. Problem solving skills were measured with a written case study patient problem test yielding three subscores: assessment, problem identification, and treatment planning. ^ Results indicated that among the demographic and educational characteristics analyzed, there was a significant difference between groups on ethnicity, bachelor degree type, admission GPA, and current GPA, but there was no significant difference on gender, age, possession of a physical therapy assistant license, and GRE score. In addition, the M P-B group achieved a significantly higher adjusted mean score on the orthopedic knowledge test after controlling for GRE scores. The S-C group achieved a significantly higher adjusted mean total score and treatment management subscore on the case study test after controlling for orthopedic knowledge test scores. These findings did not support their respective research hypotheses. There was no significant difference between groups on the assessment and problem identification subscores of the case study test. The integrated M P-B approach promoted superior retention of basic and clinical science knowledge. The results on problem solving skills were mixed. The S-C approach facilitated superior treatment planning skills, but equivalent patient assessment and problem identification skills by emphasizing all equally and exposing the students to more patients with a wider variety of orthopedic physical therapy needs than in the M P-B approach. ^

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The SCUBA HAlf degree extragalactic survey - III. Identification of radio and mid-infrared counterparts to submillimetre galaxies

Determining an accurate position for a submillimetre (submm) galaxy (SMG) is the crucial step that enables us to move from the basic properties of an SMG sample - source counts and 2D clustering - to an assessment of their detailed, multiwavelength properties, their contribution to the history of cosmic star formation and their links with present-day galaxy populations. In this paper, we identify robust radio and/or infrared (IR) counterparts, and hence accurate positions, for over two-thirds of the SCUBA HAlf-Degree Extragalactic Survey (SHADES) Source Catalogue, presenting optical, 24-μm and radio images of each SMG. Observed trends in identification rate have given no strong rationale for pruning the sample. Uncertainties in submm position are found to be consistent with theoretical expectations, with no evidence for significant additional sources of error. Employing the submm/radio redshift indicator, via a parametrization appropriate for radio-identified SMGs with spectroscopic redshifts, yields a median redshift of 2.8 for the radio-identified subset of SHADES, somewhat higher than the median spectroscopic redshift. We present a diagnostic colour-colour plot, exploiting Spitzer photometry, in which we identify regions commensurate with SMGs at very high redshift. Finally, we find that significantly more SMGs have multiple robust counterparts than would be expected by chance, indicative of physical associations. These multiple systems are most common amongst the brightest SMGs and are typically separated by 2-6 arcsec, similar to 15-20/sin i kpc at z~ 2, consistent with early bursts seen in merger simulations.

Hepatic Responses of Juvenile Fundulus heteroclitus from Pollution-adapted and Nonadapted Populations Exposed to Elizabeth River Sediment Extract.

Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Industries region of the Elizabeth River, Virginia, have passed polycyclic aromatic hydrocarbon (PAH) resistance to their offspring as evidenced by early life stage testing of developmental toxicity after exposure to specific PAHs. Our study focused on environmentally relevant PAH mixtures in the form of Elizabeth River sediment extract (ERSE). Juvenile (5 month) F1 progeny of pollution-adapted Atlantic Wood (AW) parents and of reference site (King's Creek [KC]) parents were exposed as embryos to ERSE. Liver alterations, including nonneoplastic lesions and microvesicular vacuolation, were observed in both populations. ERSE-exposed KC fish developed significantly more alterations than unexposed KC fish. Interestingly, unexposed AW killifish developed significantly more alterations than unexposed KC individuals, suggesting that AW juveniles are not fully protected from liver disease; rapid growth of juvenile fish may also be an accelerating factor for tumorigenesis. Because recent reports show hepatic tumor formation in adult AW fish, the differing responses from the 2 populations provided a way to determine whether embryo toxicity protection extends to juveniles. Future investigations will analyze older life stages of killifish to determine differences in responses related to chronic disease.