183 research outputs found

    Efficiency studies in dairy farming, Bulletin, no. 275

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    The Bulletin is a publication of the New Hampshire Agricultural Experiment Station, College of Life Sciences and Agriculture, University of New Hampshire, Durham, New Hampshire

    Criminal and Noncriminal Psychopathy: The Devil is in the Detail

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    Brooks, NS ORCiD: 0000-0003-1784-099XPsychopathy is prevalent and problematic in criminal populations, but is also found to be present in noncriminal populations. In 1992, Robert Hare declared that psychopaths may also “be found in the boardroom”, which has since been followed by an interest in the issue of noncriminal, or even successful, psychopathy. In this chapter, the paradox of criminal and noncriminal psychopathy is discussed with specific attention given to the similarities and differences that account for psychopathic personality across contexts. That psychopathy is a condition typified by a constellation of traits and behaviours requires wider research across diverse populations, and thus the streams of research related to criminal and noncriminal psychopathy are presented and the implications of these contrasting streams are explored

    Recent Change—North Sea

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    This chapter discusses past and ongoing change in the following physical variables within the North Sea: temperature, salinity and stratification; currents and circulation; mean sea level; and extreme sea levels. Also considered are carbon dioxide; pH and nutrients; oxygen; suspended particulate matter and turbidity; coastal erosion, sedimentation and morphology; and sea ice. The distinctive character of the Wadden Sea is addressed, with a particular focus on nutrients and sediments. This chapter covers the past 200 years and focuses on the historical development of evidence (measurements, process understanding and models), the form, duration and accuracy of the evidence available, and what the evidence shows in terms of the state and trends in the respective variables. Much work has focused on detecting long-term change in the North Sea region, either from measurements or with models. Attempts to attribute such changes to, for example, anthropogenic forcing are still missing for the North Sea. Studies are urgently needed to assess consistency between observed changes and current expectations, in order to increase the level of confidence in projections of expected future conditions

    Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection

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    The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRß bias. Using a retro genic model of TB10.44-11-specific CD8+ Tcells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-? production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity.This work was supported by the Portuguese Foundation for Science and Technology individual fellowship (CNA) www.fct.pt, a National Institutes of Health Grant R01 AI106725 (SMB) www.nih.gov, and a Center for AIDS Research Grant P30 AI 060354 (SMB) www.nih.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Variations in the Difference between Mean Sea Level measured either side of Cape Hatteras and Their Relation to the North Atlantic Oscillation

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    We consider the extent to which the difference in mean sea level (MSL) measured on the North American Atlantic coast either side of Cape Hatteras varies as a consequence of dynamical changes in the ocean caused by fluctuations in the North Atlantic Oscillation (NAO). From analysis of tide gauge data, we know that changes in MSL-difference and NAO index are correlated on decadal to century timescales enabling a scale factor of MSL-difference change per unit change in NAO index to be estimated. Changes in trend in the NAO index have been small during the past few centuries (when measured using windows of order 60–120 years). Therefore, if the same scale factor applies through this period of time, the corresponding changes in trend in MSL-difference for the past few centuries should also have been small. It is suggested thereby that the sea level records for recent centuries obtained from salt marshes (adjusted for long-term vertical land movements) should have essentially the same NAO-driven trends south and north of Cape Hatteras, only differing due to contributions from other processes such as changes in the Meridional Overturning Circulation or ‘geophysical fingerprints’. The salt marsh data evidently support this interpretation within their uncertainties for the past few centuries, and perhaps even for the past millennium. Recommendations are made on how greater insight might be obtained by acquiring more measurements and by improved modelling of the sea level response to wind along the shelf

    IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection

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    IL-21 is produced predominantly by activated CD4(+) T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (gamma(c)) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8(+) T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4(+) and CD8(+) T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3. We correlate these immune alterations with increased susceptibility of IL-21R(-/-) mice, which have increased lung bacterial burden and earlier mortality compared to WT mice. Finally, to causally link the immune defects with host susceptibility, we use an adoptive transfer model to show that IL-21R(-/-) T cells transfer less protection than WT T cells. These results prove that IL-21 signaling has an intrinsic role in promoting the protective capacity of T cells. Thus, the net effect of IL-21 signaling is to enhance host resistance to M. tuberculosis. These data position IL-21 as a candidate biomarker of resistance to tuberculosis.This work was supported by National Institutes of Health Grants R21 AI100766, R01 AI106725, and P01 AI073748

    Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity

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    Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome diversity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL; n = 52), high-grade (HSIL; n = 92), invasive cervical cancer (ICC; n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10%; LSIL = 11/52,21%; HSIL = 25/92,27%; ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P < 0.01), Anaerococcus tetradius (P < 0.05) and Peptostreptococcus anaerobius (P < 0.05) and lower levels of Lactobacillus jensenii (P < 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota diversity and may be involved in regulating viral persistence and disease progression

    Axillary lymph node dissection for breast cancer utilizing Harmonic Focus®

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    <p>Abstract</p> <p>Background</p> <p>For patients with axillary lymph node metastases from breast cancer, performance of a complete axillary lymph node dissection (ALND) is the standard approach. Due to the rich lymphatic network in the axilla, it is necessary to carefully dissect and identify all lymphatic channels. Traditionally, these lymphatics are sealed with titanium clips or individually sutured. Recently, the Harmonic Focus<sup>®</sup>, a hand-held ultrasonic dissector, allows lymphatics to be sealed without the utilization of clips or ties. We hypothesize that ALND performed with the Harmonic Focus<sup>® </sup>will decrease operative time and reduce post-operative complications.</p> <p>Methods</p> <p>Retrospective review identified all patients who underwent ALND at a teaching hospital between January of 2005 and December of 2009. Patient demographics, presenting pathology, treatment course, operative time, days to drain removal, and surgical complications were recorded. Comparisons were made to a selected control group of patients who underwent similar surgical procedures along with an ALND performed utilizing hemostatic clips and electrocautery. A total of 41 patients were included in this study.</p> <p>Results</p> <p>Operative time was not improved with the use of ultrasonic dissection, however, there was a decrease in the total number of days that closed suction drainage was required, although this was not statistically significant. Complication rates were similar between the two groups.</p> <p>Conclusion</p> <p>In this case-matched retrospective review, there were fewer required days of closed suction drainage when ALND was performed with ultrasonic dissection versus clips and electrocautery.</p

    Characterization of global transcription profile of normal and HPV-immortalized keratinocytes and their response to TNF treatment

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    <p>Abstract</p> <p>Background</p> <p>Persistent infection by high risk HPV types (e.g. HPV-16, -18, -31, and -45) is the main risk factor for development of cervical intraepithelial neoplasia and cervical cancer. Tumor necrosis factor (TNF) is a key mediator of epithelial cell inflammatory response and exerts a potent cytostatic effect on normal or HPV16, but not on HPV18 immortalized keratinocytes. Moreover, several cervical carcinoma-derived cell lines are resistant to TNF anti-proliferative effect suggesting that the acquisition of TNF-resistance may constitute an important step in HPV-mediated carcinogenesis. In the present study, we compared the gene expression profiles of normal and HPV16 or 18 immortalized human keratinocytes before and after treatment with TNF for 3 or 60 hours.</p> <p>Methods</p> <p>In this study, we determined the transcriptional changes 3 and 60 hours after TNF treatment of normal, HPV16 and HPV18 immortalized keratinocytes by microarray analysis. The expression pattern of two genes observed by microarray was confirmed by Northern Blot. NF-κB activation was also determined by electrophoretic mobility shift assay (EMSA) using specific oligonucleotides and nuclear protein extracts.</p> <p>Results</p> <p>We observed the differential expression of a common set of genes in two TNF-sensitive cell lines that differs from those modulated in TNF-resistant ones. This information was used to define genes whose differential expression could be associated with the differential response to TNF, such as: <it>KLK7 </it>(<it>kallikrein 7</it>), <it>SOD2 </it>(<it>superoxide dismutase 2</it>), <it>100P </it>(<it>S100 calcium binding protein P</it>), <it>PI3 </it>(<it>protease inhibitor 3, skin-derived</it>), <it>CSTA </it>(<it>cystatin A</it>), <it>RARRES1 </it>(<it>retinoic acid receptor responder 1</it>), and <it>LXN </it>(<it>latexin</it>). The differential expression of the <it>KLK7 </it>and <it>SOD2 </it>transcripts was confirmed by Northern blot. Moreover, we observed that <it>SOD2 </it>expression correlates with the differential NF-κB activation exhibited by TNF-sensitive and TNF-resistant cells.</p> <p>Conclusion</p> <p>This is the first in depth analysis of the differential effect of TNF on normal and HPV16 or HPV18 immortalized keratinocytes. Our findings may be useful for the identification of genes involved in TNF resistance acquisition and candidate genes which deregulated expression may be associated with cervical disease establishment and/or progression.</p

    On the relation between action selection and movement control in 5- to 9-month-old infants

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    Although 5-month-old infants select action modes that are adaptive to the size of the object (i.e., one- or two-handed reaching), it has largely remained unclear whether infants of this age control the ensuing movement to the size of the object (i.e., scaling of the aperture between hands). We examined 5-, 7-, and 9-month-olds’ reaching behaviors to gain more insight into the developmental changes occurring in the visual guidance of action mode selection and movement control, and the relationship between these processes. Infants were presented with a small set of objects (i.e., 2, 3, 7, and 8 cm) and a large set of objects (i.e., 6, 9, 12, and 15 cm). For the first set of objects, it was found that the infants more often performed two-handed reaches for the larger objects based on visual information alone (i.e., before making contact with the object), thus showing adaptive action mode selection relative to object size. Kinematical analyses of the two-handed reaches for the second set of objects revealed that inter-trial variance in aperture between the hands decreased with the approach toward the object, indicating that infants’ reaching is constrained by the object. Subsequent analysis showed that between hand aperture scaled to object size, indicating that visual control of the movement is adjusted to object size in infants as young as 5 months. Individual analyses indicated that the two processes were not dependent and followed distinct developmental trajectories. That is, adaptive selection of an action mode was not a prerequisite for appropriate aperture scaling, and vice versa. These findings are consistent with the idea of two separate and independent visual systems (Milner and Goodale in Neuropsychologia 46:774–785, 2008) during early infancy
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