447 research outputs found

    Desistance from Sexual Offending: A Policy and Research Agenda Whose Time Has Come

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    For the past three decades or so, criminal justice policies have been enacted under the assumption that individuals who have been convicted of a sex offense are life course persistent sex offenders. In that context, research has been heavily focused on the assessment of risk and the prediction of sexual recidivism. Simultaneously, little to no attention has been given to the majority of individuals convicted of sex offenses who are not arrested or convicted again.Researchers have witnessed a growing gap between scientific knowledge and the sociolegal response to sexual violence and abuse. The current legal landscape carries important social implications and significant life course impact for a growing number of individuals. More recently, theoretical and research breakthroughs in the study of desistance from crime and delinquency have been made that can help shed some light on desistance from sex offending. Desistance research, in the context of sex offending, however, represents serious theoretical, ethical, legal, and methodological challenges. To that end, this article introduces a special issue exploring current themes in desistance research by examining the life course of individuals convicted of a sexual offense while contextualizing their experiences of desistance.No Full Tex

    Simultaneous electrophysiology and fiber photometry in freely behaving mice

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    In vivo electrophysiology is the gold standard technique used to investigate sub-second neural dynamics in freely behaving animals. However, monitoring cell-type-specific population activity is not a trivial task. Over the last decade, fiber photometry based on genetically encoded calcium indicators (GECIs) has been widely adopted as a versatile tool to monitor cell-type-specific population activity in vivo. However, this approach suffers from low temporal resolution. Here, we combine these two approaches to monitor both sub-second field potentials and cell-type-specific population activity in freely behaving mice. By developing an economical custom-made system and constructing a hybrid implant of an electrode and a fiber optic cannula, we simultaneously monitor artifact-free mesopontine field potentials and calcium transients in cholinergic neurons across the sleep-wake cycle. We find that mesopontine cholinergic activity co-occurs with sub-second pontine waves, called P-waves, during rapid eye movement sleep. Given the simplicity of our approach, simultaneous electrophysiological recording and cell-type-specific imaging provides a novel and valuable tool for interrogating state-dependent neural circuit dynamics in vivo

    Vision in high-level football officials

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    YesOfficiating in football depends, at least to some extent, upon adequate visual function. However, there is no vision standard for football officiating and the nature of the relationship between officiating performance and level of vision is unknown. As a first step in characterising this relationship, we report on the clinically-measured vision and on the perceived level of vision in elite-level, Portuguese football officials. Seventy-one referees (R) and assistant referees (AR) participated in the study, representing 92% of the total population of elite level football officials in Portugal in the 2013/2014 season. Nine of the 22 Rs (40.9%) and ten of the 49 ARs (20.4%) were international-level. Information about visual history was also gathered. Perceived vision was assessed using the preference-values-assigned-to-global-visual-status (PVVS) and the Quality-of-Vision (QoV) questionnaire. Standard clinical vision measures (including visual acuity, contrast sensitivity and stereopsis) were gathered in a subset (n = 44, 62%) of the participants. Data were analysed according to the type (R/AR) and level (international/national) of official, and Bonferroni corrections were applied to reduce the risk of type I errors. Adopting criterion for statistical significance of p<0.01, PVVS scores did not differ between R and AR (p = 0.88), or between national- and international-level officials (p = 0.66). Similarly, QoV scores did not differ between R and AR in frequency (p = 0.50), severity (p = 0.71) or bothersomeness (p = 0.81) of symptoms, or between international-level vs national-level officials for frequency (p = 0.03) or bothersomeness (p = 0.07) of symptoms. However, international-level officials reported less severe symptoms than their national-level counterparts (p<0.01). Overall, 18.3% of officials had either never had an eye examination or if they had, it was more than 3 years previously. Regarding refractive correction, 4.2% had undergone refractive surgery and 23.9% wear contact lenses when officiating. Clinical vision measures in the football officials were similar to published normative values for young, adult populations and similar between R and AR. Clinically-measured vision did not differ according to officiating level. Visual acuity measured with and without a pinhole disc indicated that around one quarter of participants may be capable of better vision when officiating, as evidenced by better acuity (≥1 line of letters) using the pinhole. Amongst the clinical visual tests we used, we did not find evidence for above-average performance in elite-level football officials. Although the impact of uncorrected mild to moderate refractive error upon officiating performance is unknown, with a greater uptake of eye examinations, visual acuity may be improved in around a quarter of officials.Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2013

    Biochemical and immuno-histochemical localization of type IIA procollagen in annulus fibrosus of mature bovine intervertebral disc

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    For next generation tissue-engineered constructs and regenerative medicine to succeed clinically, the basic biology and extracellular matrix composition of tissues that these repair techniques seek to restore have to be fully determined. Using the latest reagents coupled with tried and tested methodologies, we continue to uncover previously undetected structural proteins in mature intervertebral disc. In this study we show that the embryonic type IIA procollagen isoform (containing a cysteine-rich amino propeptide) was biochemically detectable in the annulus fibrosus of both calf and mature steer caudal intervertebral discs, but not in the nucleus pulposus where the type IIB isoform was predominantly localized. Specifically, the triple-helical type IIA procollagen isoform immunolocalized in the outer margins of the inner annulus fibrosus. Triple helical processed type II collagen exclusively localized within the inter-lamellae regions and with type IIA procollagen in the intra-lamellae regions. Mass spectrometry of the α1(II) collagen chains from the region where type IIA procollagen localized showed high 3-hydroxylation of Proline-944, a post-translational modification that is correlated with thin collagen fibrils as in the nucleus pulposus. The findings implicate small diameter fibrils of type IIA procollagen in select regions of the annulus fibrosus where it likely contributes to the organization of collagen bundles and structural properties within the type I-type II collagen transition zone

    Journal of Physics: conference Series

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    The convergent close-coupling calculations of e+-Li and e+-Na collisions are reported. The target is treated as one active electron interacting with an inert ion core. The positronium formation channels are taken into account explicitly utilizing both negative- and positive-energy Laguerre-based states. A large number of channels and high partial waves are used to ensure the convergence of the cross sections

    Apoptosis signal-regulating kinase 1 inhibition attenuates human airway smooth muscle growth and migration in chronic obstructive pulmonary disease

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    © 2018 The Author(s). Increased airway smooth muscle (ASM) mass is observed in chronic obstructive pulmonary disease (COPD), which is correlated with disease severity and negatively affects lung function in these patients. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) activated by various stress stimuli, including reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and is known to regulate cell proliferation. ASM cells from COPD patients are hyperproliferative to mitogens in vitro. However, the role of ASK1 in ASM growth is not established. Here, we aim to determine the effects of ASK1 inhibition on ASM growth and pro-mitogenic signaling using ASM cells from COPD patients. We found greater expression of ASK1 in ASM bundles of COPD lung when compared with non-COPD. Pre-treatment of ASM cells with highly selective ASK1 inhibitor, TC ASK 10 resulted in a dose-dependent reduction in mitogen (FBS, PDGF, and EGF; 72 h)-induced ASM growth as measured by CyQUANT assay. Further, molecular targetting of ASK1 using siRNA in ASM cells prevented mitogen-induced cell growth. In addition, to anti-mitogenic potential, ASK1 inhibitor also prevented TGFβ1-induced migration of ASM cells in vitro. Immunoblotting revealed that anti-mitogenic effects are mediated by C-Jun N-terminal kinase (JNK) and p38MAP kinase-signaling pathways as evident by reduced phosphorylation of downstream effectors JNK1/2 and p38MAP kinases, respectively, with no effect on extracellular signal-regulated kinase (ERK) 1/2 (ERK1/2). Collectively, these findings establish the anti-mitogenic effect of ASK1 inhibition and identify a novel pathway that can be targetted to reduce or prevent excessive ASM mass in COPD

    Many-body theory of positron-atom interactions

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    A many-body theory approach is developed for the problem of positron-atom scattering and annihilation. Strong electron-positron correlations are included non-perturbatively through the calculation of the electron-positron vertex function. It corresponds to the sum of an infinite series of ladder diagrams, and describes the physical effect of virtual positronium formation. The vertex function is used to calculate the positron-atom correlation potential and nonlocal corrections to the electron-positron annihilation vertex. Numerically, we make use of B-spline basis sets, which ensures rapid convergence of the sums over intermediate states. We have also devised an extrapolation procedure that allows one to achieve convergence with respect to the number of intermediate-state orbital angular momenta included in the calculations. As a test, the present formalism is applied to positron scattering and annihilation on hydrogen, where it is exact. Our results agree with those of accurate variational calculations. We also examine in detail the properties of the large correlation corrections to the annihilation vertex.Comment: 25 pages, 16 figure

    Chloroquine: Autophagy inhibitor, antimalarial, bitter taste receptor agonist in fight against COVID-19, a reality check?

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    The recent SARS-CoV-2 pandemic poses one of the greatest challenges to modern medicine. Therefore, identification of new therapeutic strategies seems essential either based on novel vaccines or drugs or simply repurposing existing drugs. Notably, due to their known safety profile, repurposing of existing drugs is the fastest and highly efficient approach to bring a therapeutic to a clinic for any new indication. One such drug that has been used extensively for decades is chloroquine (CQ, with its derivatives) either for malaria, lupus and rheumatoid arthritis. Accumulating body of evidence from experimental pharmacology suggests that CQ and related analogues also activate certain pathways that can potentially be exploited for therapeutic gain. For example, in the airways, this has opened an attractive avenue for developing novel bitter taste ligands as a new class of bronchodilators for asthma. While CQ and its derivatives have been proposed as a therapy in COVID-19, it remains to be seen whether it really work in the clinic? To this end, our perspective aims to provide a timely yet brief insights on the existing literature on CQ and the controversies surrounding its use in COVID-19. Further, we also highlight some of cell-based mechanism(s) that CQ and its derivatives affect in mediating variety of physiological responses in the cell. We believe, data emanating from the clinical studies and continual understanding of the fundamental mechanisms may potentially help in designing effective therapeutic strategies that meets both efficacy and safety criteria for COVID-19

    Heidelberg Anterion Swept-Source OCT Corneal Epithelial Thickness Mapping: Repeatability and Agreement With Optovue Avanti

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    PURPOSE: To assess the repeatability of corneal epithelial thickness mapping in virgin, post-laser refractive surgery (PLRS), and keratoconic eyes using a novel swept-source optical coherence tomographer (SS-OCT), and to determine the agreement of the measurements with a validated spectral-domain (SD) OCT. METHODS: Analysis of 90 virgin, 46 PLRS, and 122 keratoconic eyes was performed. Three consecutive measurements of each eye were acquired with the Anterion SS-OCT and Avanti SD-OCT devices, and averages of the epithelial thickness mapping were calculated in the central 2-mm zone and in the 2- to 5-mm and 5- to 7-mm diameter rings. The repeatability was analyzed using pooled within-subject standard deviation (Sw). The agreement was assessed by Bland-Altman analysis and paired t tests. RESULTS: The repeatability ranges of the Anterion and Avanti epithelial thickness mapping measurements were Sw: 0.60 to 1.36 µm and Sw: 0.75 to 1.96 µm, respectively. The 95% limits of agreement of the Anterion and Avanti were 0.826 to 8.297. All values of the thickness measurements with the Anterion were lower than those of the Avanti, with the mean differences being 4.06 ± 1.81, 3.26 ± 2.52, and 3.68 ± 2.51 µm in virgin, PLRS, and keratoconic eyes, respectively (P < .001 for all). CONCLUSIONS: The repeatability of the Anterion's epithelial thickness mapping was higher than that of the Avanti. In terms of the agreement between the Anterion and Avanti, the epithelium measured by the Anterion was always thinner than that of the Avanti, making their interchangeable use unsuitable without corrections
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